Trial Outcomes & Findings for The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE (NCT NCT03635788)

Last Updated: 2025-09-02

Results Overview

Regimen failure was defined as the occurrence of the earlier of the following two events * virologic failure (defined as two consecutive HIV-1 RNA \>200 copies/mL after Step 2 randomization * Permanent discontinuation of randomized study treatment prior to or at Week 48 visit Cumulative probability was calculated by Kaplan-Meier method.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

456 participants

Primary outcome timeframe

From Step 2 randomization to Step 2, Week 48 visit (up to 50 weeks)

Results posted on

2025-09-02

Participant Flow

Participants were enrolled at 33 Clinical Research Sites (CRSs) in the United States between March 28, 2019 and February 12, 2024. A total of 456 participants enrolled to study. After completing Step 1, 308 participants were randomized to Step 2. Enrollment to Step 3 and Step 4 will be updated upon study completion.

Step 1 eligibility violations were identified in three participants. One participant was found to have missed the screening confirmatory HBV DNA test. Two participants were found to have past exclusionary mutations after enrolled to Step 2. All three participants were excluded from all analyses. 453 eligible participants were enrolled to Step 1. 306 eligible participants were randomized to Step 2 after completing Step 1.

Participant milestones

Participant milestones
Measure	Step 1 SOC In Step 1, participants received SOC oral ART regimen for up to 24 weeks.	Step 2 Arm A: LA-ART In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants continued SOC oral ART regimen for 52 weeks.
Step 1 STARTED	453	0	0
Step 1 COMPLETED	360	0	0
Step 1 NOT COMPLETED	93	0	0
Step 2 STARTED	0	152	154
Step 2 COMPLETED	0	76	74
Step 2 NOT COMPLETED	0	76	80

Reasons for withdrawal

Reasons for withdrawal
Measure	Step 1 SOC In Step 1, participants received SOC oral ART regimen for up to 24 weeks.	Step 2 Arm A: LA-ART In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants continued SOC oral ART regimen for 52 weeks.
Step 1 Death	1	0	0
Step 1 Lost to Follow-up	31	0	0
Step 1 Pregnancy	1	0	0
Step 1 Protocol Violation	8	0	0
Step 1 Withdrawal by Subject	13	0	0
Step 1 Other reasons	12	0	0
Step 1 On Step 1 as of February 12, 2024	27	0	0
Step 2 Lost to Follow-up	0	8	15
Step 2 Withdrawal by Subject	0	6	6
Step 2 Death	0	2	0
Step 2 Incarceration	0	2	0
Step 2 Non-Compliance With Study Requirements	0	1	1
Step 2 Confounding Medical Condition	0	0	1
Step 2 Out Of State With No Plan To Return	0	1	0
Step 2 Switched To Injectables	0	0	1
Step 2 On Step 2 as of February 12, 2024	0	56	56

Baseline Characteristics

Step 1 baseline measurement included 453 participants who were enrolled in the study. Step 2 baseline measurement included 306 participants who were randomized to Step 2.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From Step 2 randomization to Step 2, Week 48 visit (up to 50 weeks)

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Cumulative Probability of Regimen Failure in Step 2 at Any Time Post Randomization and Week 48 Visit	22.8 cumulative percent probability of event	41.2 cumulative percent probability of event

SECONDARY outcome

Timeframe: From Step 2 randomization to Step 2, Week 48 visit (up to 50 weeks)

Virologic failure was defined as two consecutive HIV-1 RNA \>200 copies/mL after Step 2 randomization and up to Step 2 Week 48 visit, regardless of the time between them. Cumulative probability was calculated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Cumulative Probability of Virologic Failure in Step 2 at Any Time Post Randomization to Week 48 Visit	6.8 cumulative percent probability of event	28.2 cumulative percent probability of event

SECONDARY outcome

Timeframe: From after Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

Treatment-related failure was defined as the occurrence of the earlier of virologic failure or permanent Step 2 treatment discontinuation due to treatment-related adverse events. Cumulative probability was calculated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Cumulative Probability of the Treatment-related Failure in Step 2 at Any Time Post Randomization to Week 48 Visit	8.9 cumulative percent probability of event	28.1 cumulative percent probability of event

SECONDARY outcome

Timeframe: from Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

Population: The analysis population was restricted to participants randomized at least 50 weeks prior to February 12, 2024.

Virologic non-success was defined by the US Food and Drug Administration (FDA) Snapshot algorithm

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=94 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=96 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Number of Participants With Virologic Non-success (>= 50 Copies/ml) On treatment but missing data	2 Participants	1 Participants
Number of Participants With Virologic Non-success (>= 50 Copies/ml) HIV-1 RNA < 50 copies/ml	62 Participants	49 Participants
Number of Participants With Virologic Non-success (>= 50 Copies/ml) HIV-1 RNA >= 50 copies/ml	14 Participants	33 Participants
Number of Participants With Virologic Non-success (>= 50 Copies/ml) Treatment Discontinuation due to AE or Death	6 Participants	0 Participants
Number of Participants With Virologic Non-success (>= 50 Copies/ml) Treatment Discontinuation due to other reasons with HIV-1 RNA < 50 copies/ml	10 Participants	13 Participants

SECONDARY outcome

Timeframe: From Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

Population: The analysis population was restricted to participants randomized at least 50 weeks prior to February 12, 2024.

Virologic non-success was defined by the US Food and Drug Administration (FDA) Snapshot algorithm

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=94 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=96 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Number of Participants With Virologic Non-success (>= 200 Copies/ml) HIV-1 RNA < 200 copies/ml	69 Participants	55 Participants
Number of Participants With Virologic Non-success (>= 200 Copies/ml) HIV-1 RNA >= 200 copies/ml	5 Participants	25 Participants
Number of Participants With Virologic Non-success (>= 200 Copies/ml) Treatment Discontinuation due to AE or Death	6 Participants	0 Participants
Number of Participants With Virologic Non-success (>= 200 Copies/ml) Treatment Discontinuation due to other reasons with HIV-1 RNA < 200 copies/ml	12 Participants	15 Participants
Number of Participants With Virologic Non-success (>= 200 Copies/ml) On treatment but missing data	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Measured from Step 1 entry through Step 1, Week 20 visit

Population: Step 1 used Intention-to-Treat (ITT) population which was defined as all eligible participants who registered to Step 1, regardless of status on treatment.

Summarized the percentage of participants with plasma HIV-1 RNA level less than 50 copies/mL by study visit

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=453 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Baseline	21 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Week 4	57 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Week 8	47 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Week 12	55 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Week 16	56 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1 Week 20	63 percentage of participants	—

SECONDARY outcome

Timeframe: Measured from Step 1 entry through Step 1, Week 20 visit

Population: Step 1 used Intention-to-Treat (ITT) population which was defined as all eligible participants who registered to Step 1, regardless of status on treatment.

Summarized the percentage of participants with plasma HIV-1 RNA level less than 200 copies/mL by study visit

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=453 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Baseline	34 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Week 4	74 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Week 8	68 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Week 12	74 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Week 16	67 percentage of participants	—
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 1 Week 20	74 percentage of participants	—

SECONDARY outcome

Timeframe: Measured from Step 2 entry through Step 2, Week 48 visit

Summarized the percentage of participants with plasma HIV-1 RNA level less than 50 copies/mL by study visit, and randomized treatment.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Baseline	72 percentage of participants	81 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Week 8	88 percentage of participants	68 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Week 16	84 percentage of participants	67 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Week 24	93 percentage of participants	69 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Week 36	90 percentage of participants	69 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 2 Week 48	87 percentage of participants	78 percentage of participants

SECONDARY outcome

Timeframe: Measured from Step 2 entry through Step 2, Week 48 visit

Summarized the percentage of participants with plasma HIV-1 RNA level less than 200 copies/mL by study visit, and randomized treatment.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Baseline	84 percentage of participants	93 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Week 8	95 percentage of participants	81 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Week 16	97 percentage of participants	80 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Week 24	98 percentage of participants	77 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Week 36	98 percentage of participants	81 percentage of participants
Percentage of Participants With Plasma HIV-1 RNA Level Less Than 200 Copies/mL at Scheduled Study Visits on Steps 2 Week 48	95 percentage of participants	86 percentage of participants

SECONDARY outcome

Timeframe: Measured from Step 2 randomization through Step 2, Week 48 (up to 50 weeks)

Permanent Step 2 treatment discontinuation was defined as premature discontinuation of randomized study treatment. Cumulative probability was calculated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Cumulative Probability of Discontinuation of Randomized Treatment in Step 2	19.8 cumulative percent probability of event	28.2 cumulative percent probability of event

SECONDARY outcome

Timeframe: HIVTSQ status was collected on both arms at Step 2 entry and Week 24, and also at Week 48 for those randomized to SOC. At Week 48, HIVTSQ change was collected for participants on the LA-ART arm.

Population: Intention-to-Treat (ITT) Population was defined as all eligible participants who were randomized to the treatment arms, regardless of status on randomized treatment. Participants were assessed according to their randomized treatment, regardless of the treatment they received. Data were not collected from participants for HIVTSQ status for participants in LA-ART arm at week 24 or HIVTSQ change for participants in SOC arm at week 48

The questionnaire had 12 items rated using a 7-point Likert scale. Results were summarized as a total score that included 11 items, with the "pain/discomfort" item reported separately. 1. The HIVTSQ "status" measured participant satisfaction with their current treatment with individual item rated ranging from 0 ("very dissatisfied") to 6 ("very satisfied") and the total score ranging from 0 to 66, where higher scores indicated a greater level of satisfaction with their HIV-1 treatment. 2. The HIVTSQ "change" measured change in treatment satisfaction between a participant's previous and current treatment. The individual items were rated from -3 ("much less satisfied") to 3 ("much more satisfied") with a total score ranging from -33 to 33.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 0, 11-item total score	63 score on a scale Interval 55.0 to 66.0	62 score on a scale Interval 53.0 to 66.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 0, Satisfaction with pain/discomfort	6 score on a scale Interval 5.0 to 6.0	6 score on a scale Interval 4.0 to 6.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 24, 11-item total score	66 score on a scale Interval 60.0 to 66.0	62 score on a scale Interval 51.0 to 66.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 24, Satisfaction with pain/discomfort	6 score on a scale Interval 5.0 to 6.0	6 score on a scale Interval 5.0 to 6.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 48,11-item total score	—	63 score on a scale Interval 51.0 to 66.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ status Week 48, Satisfaction with pain/discomfort	—	6 score on a scale Interval 5.0 to 6.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ change Week 24, 11-item total score	0 score on a scale Interval 0.0 to 4.0	0 score on a scale Interval 0.0 to 1.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ change Week 24, Satisfaction with pain/discomfort	0 score on a scale Interval 0.0 to 0.0	0 score on a scale Interval 0.0 to 0.0
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ change Week 48,11-item total score	33 score on a scale Interval 31.0 to 33.0	—
Median Summary Score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) in Step 2 HIVTSQ change Week 48, Satisfaction with pain/discomfort	3 score on a scale Interval 2.0 to 3.0	—

SECONDARY outcome

Timeframe: Measured from Step 2 randomization through Step 2, Week 52

Population: Analysis population was restricted to the participants who initiated injections

Delayed injection was defined as 36-56 days from the previous injection. Missed injection was defined as the duration from the previous injection was longer than 56 days.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=141 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Number of Participants With Missed or Delayed Injections for Participants Who Received LA ART in Step 2 Delayed injection	32 participants	—
Number of Participants With Missed or Delayed Injections for Participants Who Received LA ART in Step 2 Missed injection	15 participants	—

SECONDARY outcome

Timeframe: Step 1 entry, Weeks 12 and 20.

Population: Step 1 used Intention-to-Treat (ITT) population which was defined as all eligible participants who registered to Step 1, regardless of status on treatment.

HIV Treatment Adherence Self-Efficacy Scale was a 12-item measure used to measure social and psychological determinants of adherence to ART among individuals living with HIV. The response scale to each individual item ranged from 0 ("cannot do at all") to 10 ("completely certain can do"). The total score reported was the average of all item scores, ranging from 0 to 10, with higher scores indicating higher adherence self-efficacy.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=453 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 1 Week 0	9 score on a scale Interval 7.0 to 10.0	—
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 1 Week 12	9 score on a scale Interval 7.0 to 10.0	—
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 1 Week 20	9 score on a scale Interval 8.0 to 10.0	—

SECONDARY outcome

Timeframe: As Step 2 Week 0, Week 24 and Week 48

Population: As-treated Population was defined as all eligible participants who were randomized to the treatment arms and received at least one dose of a randomized treatment. Participants were assessed according to actual treatment strategy received.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=151 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=152 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 2 Week 0	9 score on a scale Interval 8.0 to 10.0	9 score on a scale Interval 8.0 to 10.0
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 2 Week 24	10 score on a scale Interval 8.0 to 10.0	10 score on a scale Interval 8.0 to 10.0
Median of Summary Scores of HIV Treatment Adherence Self-Efficacy Scale in Step 2 Week 48	10 score on a scale Interval 9.0 to 10.0	10 score on a scale Interval 8.0 to 10.0

SECONDARY outcome

Timeframe: Measured at Step 1 screening/entry and at the time of virologic failure in Step 2

Population: Analysis population was restricted to the participants with virologic failure

Samples for HIV-1 resistance testing were collected at virologic failure confirmation visit. HIV-1 drug resistance mutations were determined using the IAS October/November 2022 Update of the Drug Resistance Mutations in HIV-1. New drug resistance mutations were defined as those detected at or after virologic failure which were not present at Step 1 screening/baseline. Virologic failure defined as two consecutive HIV-1 RNA \> 200 copies/mL after Step 2 randomization, regardless of the time between them.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=6 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=34 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Number of Participants With New Drug-resistance Mutations in Participants With Virologic Failure in Step 2 Sample Not Collected	0 Participants	3 Participants
Number of Participants With New Drug-resistance Mutations in Participants With Virologic Failure in Step 2 With New Mutation	2 Participants	2 Participants
Number of Participants With New Drug-resistance Mutations in Participants With Virologic Failure in Step 2 Without New Mutation	3 Participants	20 Participants
Number of Participants With New Drug-resistance Mutations in Participants With Virologic Failure in Step 2 Discontinued study without a confirmation sample	0 Participants	5 Participants
Number of Participants With New Drug-resistance Mutations in Participants With Virologic Failure in Step 2 Not done; HIV-1 RNA < 400 copies/mL	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Measured from Step 2 randomization through Step 2, Week 52

Population: Analysis population was restricted to participants who initiated injection

Summarized and tabulated by number of participants with at least 1 injection site reactions. Severity Grade: 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Life-Threatening, 5 = Death

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=141 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Grade 1 or Higher Injection Site Reactions (ISR) During Step 2	60 percentage of participant	—

SECONDARY outcome

Timeframe: Step 2 week 48, premature treatment visit, and study discontinuation visit

Population: Analysis population was restricted to the participants who had the indicated visit, either week 48, premature treatment discontinuation, or premature study discontinuation.

The Dichotomous Preference Questionnaire were: 1. Monthly injections of Long-Acting HIV Treatment 2. Daily oral HIV

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=85 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants Who Preferred Monthly Injections of Long-Acting HIV Treatment or Daily Oral HIV Treatment at Each Visit At Week 48, Daily oral HIV Treatment	5 percentage of participants	—
Percentage of Participants Who Preferred Monthly Injections of Long-Acting HIV Treatment or Daily Oral HIV Treatment at Each Visit At Week 48, Monthly injections of Long-Acting HIV Treatment	95 percentage of participants	—
Percentage of Participants Who Preferred Monthly Injections of Long-Acting HIV Treatment or Daily Oral HIV Treatment at Each Visit At Premature treatment discontinuation, Daily oral HIV Treatment	50 percentage of participants	—
Percentage of Participants Who Preferred Monthly Injections of Long-Acting HIV Treatment or Daily Oral HIV Treatment at Each Visit At Premature treatment discontinuation, Monthly injections	50 percentage of participants	—
Percentage of Participants Who Preferred Monthly Injections of Long-Acting HIV Treatment or Daily Oral HIV Treatment at Each Visit At Premature study discontinuation, Monthly injections	100 percentage of participants	—

SECONDARY outcome

Timeframe: At Step 2 entry and Step 2, Week 8

Population: Modified Intention-to-Treat (mITT) Population was defined as all eligible participants who were randomized to the treatment arms and received at least one dose of study treatment at or after randomization.

The responses included: Not at all upset or disappointed, Not very upset or disappointed, Somewhat upset or disappointed, Extremely upset or disappointed, Undecided

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=151 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=152 Participants In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 0, Not at all upset or disappointed	48 percentage of participants	49 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 0, Not very upset or disappointed	13 percentage of participants	9 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Somewhat upset or Week 0, disappointed	18 percentage of participants	18 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 0, Extremely upset or disappointed	11 percentage of participants	11 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 0, Undecided	9 percentage of participants	14 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 8, Not at all upset or disappointed	43 percentage of participants	37 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 8, Not very upset or disappointed	16 percentage of participants	14 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 8, Somewhat upset or disappointed	24 percentage of participants	23 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 8, Extremely upset or disappointed	12 percentage of participants	17 percentage of participants
Percentage of Participants With Opinions About Conditional Economic Incentive (CEI) Withdrawal Week 8, Undecided	5 percentage of participants	10 percentage of participants

SECONDARY outcome

Timeframe: Step 1 entry, Step 1 Weeks 12, and Step 1 Weeks 20

Population: Step 1 used Intention-to-Treat (ITT) population which was defined as all eligible participants who registered to Step 1, regardless of status on treatment.

HIV-ASES was a 12-item measure used to measure social and psychological determinants of adherence to ART among individuals living with HIV. The response scale to each individual item ranged from 0 ("cannot do at all") to 10 ("completely certain can do"). The total score reported was the average of all item scores, ranging from 0 to 10, with higher scores indicating higher adherence self-efficacy.

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=453 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Median of Average Total Score of Step 1 HIV Treatment Adherence Self-Efficacy Scale Score (HIV-ASES) Week 0	9 score on a scale Interval 7.0 to 10.0	—
Median of Average Total Score of Step 1 HIV Treatment Adherence Self-Efficacy Scale Score (HIV-ASES) Week 12	9 score on a scale Interval 7.0 to 10.0	—
Median of Average Total Score of Step 1 HIV Treatment Adherence Self-Efficacy Scale Score (HIV-ASES) Week 20	9 score on a scale Interval 8.0 to 10.0	—

SECONDARY outcome

Timeframe: At Step 2 entry, Step 2 week 4, Step 2 week 8, step 2 week 16, step 2 week 24, step 2 week 36, Step 2 week 48, and Step 2 week 52

Population: As-treated Population was defined as all eligible participants who were randomized to the treatment arms and received at least one dose of a randomized treatment.

The outcome was defined as participants with at least one dose missed in the last 30 days at each visit

Outcome measures

Outcome measures
Measure	Step 2 Arm A: LA ART n=152 Participants In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC In Step 2, participants received SOC oral ART regimen for 52 weeks.
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 0	57 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 4	59 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 8	62 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 16	64 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 24	64 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 36	66 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 48	66 percentage of participants	—
Percentage of Participants With Missed Treatment Doses Among Participants Who Randomized to SOC Arm in Step 2 Week 52	59 percentage of participants	—

Adverse Events

Step 1 SOC

Serious events: 38 serious events

Other events: 73 other events

Deaths: 1 deaths

Step 2 Arm A: LA-ART

Serious events: 21 serious events

Other events: 40 other events

Deaths: 2 deaths

Step 2 Arm B: SOC

Serious events: 16 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

Phone: (301) 628-3348

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Step 1 SOC n=453 participants at risk In Step 1, participants received SOC oral ART regimen for up to 24 weeks.	Step 2 Arm A: LA-ART n=152 participants at risk In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 participants at risk In Step 2, participants received SOC oral ART regimen for 52 weeks.
Hepatobiliary disorders Cirrhosis alcoholic	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Cardiac disorders Acute left ventricular failure	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Cardiac disorders Acute myocardial infarction	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Cardiac disorders Cardiac failure acute	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Cardiac disorders Coronary artery disease	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Cardiac disorders Left ventricular failure	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Eye disorders Photophobia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Abdominal pain	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Diarrhoea	0.44% 2/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Duodenitis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Gastritis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Nausea	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Peptic ulcer	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Pyrexia	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Hepatobiliary disorders Alcoholic liver disease	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Hepatobiliary disorders Cholecystitis acute	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Abdominal sepsis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Abscess limb	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Anal abscess	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Appendicitis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Bronchitis viral	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Cellulitis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Cryptococcal fungaemia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Disseminated cryptococcosis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Gastroenteritis	0.44% 2/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Gastroenteritis shigella	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Herpes zoster disseminated	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Influenza	0.44% 2/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Mastitis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Neurosyphilis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Oesophageal candidiasis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Oropharyngeal candidiasis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Periumbilical abscess	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pharyngitis streptococcal	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pneumocystis jirovecii pneumonia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pneumonia	0.66% 3/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.9% 3/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pulmonary tuberculosis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Rotavirus infection	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Sepsis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Shigella infection	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN

Other adverse events
Measure	Step 1 SOC n=453 participants at risk In Step 1, participants received SOC oral ART regimen for up to 24 weeks.	Step 2 Arm A: LA-ART n=152 participants at risk In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.	Step 2 Arm B: SOC n=154 participants at risk In Step 2, participants received SOC oral ART regimen for 52 weeks.
Blood and lymphatic system disorders Anaemia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Blood and lymphatic system disorders Neutropenia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Abdominal pain	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Anogenital dysplasia	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Diarrhoea	0.66% 3/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Food poisoning	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Gastritis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Nausea	0.44% 2/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Gastrointestinal disorders Vomiting	0.66% 3/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Chest pain	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Chills	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Facial discomfort	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Fatigue	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Injection site nodule	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Injection site pain	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	3.3% 5/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Injection site swelling	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	1.3% 2/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Peripheral swelling	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
General disorders Pyrexia	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Immune system disorders Immune reconstitution inflammatory syndrome	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Acute hepatitis C	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Breakthrough COVID-19	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Bronchitis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations COVID-19	1.5% 7/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	2.6% 4/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	5.8% 9/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Cellulitis	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Epstein-Barr virus infection	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Hepatitis A	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Joint abscess	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pelvic abscess	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pneumocystis jirovecii pneumonia	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pneumonia aspiration	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Pneumonia respiratory syncytial viral	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Suspected COVID-19	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Infections and infestations Tonsillitis	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Fall	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Foot fracture	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Incision site pain	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Limb injury	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.65% 1/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN
Injury, poisoning and procedural complications Overdose	0.22% 1/453 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.66% 1/152 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN	0.00% 0/154 • From Step 1 entry to through Step 1, Week 24 and from Step 2 entry to through Step 2 Week 52 or premature study discontinuation. Summary of Adverse Events will be updated with Step 3 and 4 upon study completion. All grade ≥3, led to a change in study treatment/intervention regardless of grade, meeting SAE definition (as defined by ICH criteria) or EAE reporting requirement New diagnosis of diabetes or pre-existing diabetes with ≥Grade 2 diabetes,hepatitis B, hepatitis C, COVID-19 or SARS-CoV-2 infection, Cancer, Tuberculosis All ≥Grade 2 neurologic and psychiatric events, seizures regardless of grade Any bone fracture, ALT ≥3x ULN AND total bilirubin ≥2x ULN