Trial Outcomes & Findings for A Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma (NCT NCT01609010)

Last Updated: 2014-09-08

Results Overview

Treatment failure was defined as an event of any of the following: progressive disease while receiving study treatment, death due to any cause, or the initiation of another type of treatment due to stable disease, progressive disease or relapse, or intolerance to study treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

313 participants

Primary outcome timeframe

Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Results posted on

2014-09-08

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Monotherapy Participants rituximab received 375 milligrams per square meter (mg/m\^2), intravenously (IV), once weekly for 4 weeks. Participants who achieved minor response (MR), partial response (PR), or complete response (CR) after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + Interferon (IFN) Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-alpha2a (IFN-α2a), 3 million international units per day (MIU/day), subcutaneously (SC), during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Overall Study STARTED	156	157
Overall Study Entering Cycle 2	120	124
Overall Study COMPLETED	113	120
Overall Study NOT COMPLETED	43	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Monotherapy Participants rituximab received 375 milligrams per square meter (mg/m\^2), intravenously (IV), once weekly for 4 weeks. Participants who achieved minor response (MR), partial response (PR), or complete response (CR) after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + Interferon (IFN) Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-alpha2a (IFN-α2a), 3 million international units per day (MIU/day), subcutaneously (SC), during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Overall Study Stable disease (SD)	22	16
Overall Study Progressive disease (PD)	8	10
Overall Study Adverse Event	3	6
Overall Study Withdrawal by Subject	2	2
Overall Study Other	2	0
Overall Study Other malignancy	1	0
Overall Study Pathology review	2	1
Overall Study Protocol Violation	1	1
Overall Study New cancer	1	0
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

A Study of MabThera/Rituxan (Rituximab) Alone and in Combination With Roferon-A in Patients With Follicular or Other CD20+ Low-Grade (Indolent) Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Total n=313 Participants Total of all reporting groups
Age, Continuous	59.1 years STANDARD_DEVIATION 11.6 • n=5 Participants	57.2 years STANDARD_DEVIATION 10.8 • n=7 Participants	58.1 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	82 Participants n=7 Participants	160 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	75 Participants n=7 Participants	153 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (BL), Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Treatment Failure - Percentage of Participants With an Event	68 percentage of participants	67 percentage of participants

PRIMARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

The median time, in months, between randomization and treatment failure event determined using Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Treatment Failure - Time to Event	21.5 months Interval 13.6 to 26.5	28.0 months Interval 20.7 to 41.0

SECONDARY outcome

Timeframe: Weeks 10 and 16

Population: ITT population; number (n) equals (=) number of participants assessed for the specified parameter at a given visit.

CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes greater than (\>) 1 centimeter (cm) or nodes \>1.5 cm observed in computerized axial tomography (CAT) scan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate. PR was defined as a decrease of greater than or equal to (≥) 50 percent (%) compared with the BL value in the sum of the products of the two largest perpendicular diameters in all measurable and evaluable lesions; and a ≥50% reduction of the size from BL if hepato-splenomegaly was present.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) Week 10, Cycle 1 (n=156,157)	54 percentage of participants Interval 46.0 to 62.0	59 percentage of participants Interval 51.0 to 67.0
Percentage of Participants Achieving Complete Response (CR), Unconfirmed CR (CRu), or Partial Response (PR) Week 16, Cycle 2 (n=123,124)	74 percentage of participants Interval 65.0 to 81.0	82 percentage of participants Interval 74.0 to 89.0

SECONDARY outcome

Timeframe: Weeks 10 and 16

Population: ITT population; n=number of participants assessed for the specified parameter at a given visit.

CR was defined as the complete disappearance of all previously detectable disease signs; the absence of palpable lymph nodes \>1 cm or nodes \>1.5 cm observed in CATscan; and negative bone marrow pathology, if initially positive. CRu was defined as CR, except that bone marrow results were indeterminate.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Percentage of Participants Achieving CR or CRu Week 10, Cycle 1 (n=156,157)	8 percentage of participants Interval 5.0 to 14.0	9 percentage of participants Interval 5.0 to 15.0
Percentage of Participants Achieving CR or CRu Week 16, Cycle 2 (n=123,124)	24 percentage of participants Interval 17.0 to 33.0	41 percentage of participants Interval 32.0 to 50.0

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

Response duration was defined as the period between the date for first observation of CR, CRu or PR and the date of progressive disease (PD), censored observation or death of any cause. Response duration was also assessed for response defined as CR only. Response duration was calculated among responders (CR+CRu+PR) with cutoffs for follow-up applied.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=102 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=113 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Duration of Response - Percentage of Participants With an Event CR, CRu, and PR (n=102,113)	63 percentage of participants	65 percentage of participants
Duration of Response - Percentage of Participants With an Event CR and CRu only (n=62,73)	44 percentage of participants	53 percentage of participants
Duration of Response - Percentage of Participants With an Event CR only (n=50,62)	38 percentage of participants	48 percentage of participants

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population; n=number of participants assessed for the specified parameter at a given visit. Only participants with a response (CR+CRu+PR, CR+CRu, or CR only) were included in the analysis.

The median time, in months, from the date of the first observation of CR, CRu, or PR and the date of progressive disease (PD), censored observation, or death due to any cause. PD was defined as an increase of \>50% compared to BL in the sum of the product of the two largest perpendicular parameters of measurable lymphoma, or the occurrence of new lesions. One month=30.4 days. Response duration was calculated amongst responders (CR+CRu+PR) with cutoffs for follow-up applied.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Duration of Response CR+CRu+PR (n=102,113)	22.0 months Interval 15.9 to 32.3	30.0 months Interval 20.1 to 39.8
Duration of Response CR+CRu only (n=62,73)	NA months Interval 23.0 to The median and upper limit of the 95% confidence interval (CI) were not estimable due to censoring.	44.4 months Interval 33.0 to The upper limit of the 95% CI was not estimable due to censoring.
Duration of Response CR only (n=50,62)	59.5 months Interval 23.1 to The upper limit of the 95% CI was not estimable due to censoring.	50.7 months Interval 26.7 to The upper limit of the 95% CI was not estimable due to censoring.

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

A disease progression event was defined as tumor progression or death due to any cause (or a censored observation).

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Disease Progression - Percentage of Participants With an Event	60 percentage of participants	62 percentage of participants

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

The median time, in months, from randomization to disease progression event assessed using Kaplan-Meier estimates. One month=30.4 days

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Time to Disease Progression	25.0 months Interval 18.7 to 39.8	32.0 months Interval 21.7 to 40.3

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

An overall survival event was defined as death due to any cause.

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Overall Survival (OS) - Percentage of Participants With an Event	13 percentage of participants	11 percentage of participants

SECONDARY outcome

Timeframe: BL, Week 10 and 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period

Population: ITT population

The median time, in months, from randomization to OS event assessed using Kaplan-Meier estimates. One month=30.4 days

Outcome measures

Outcome measures
Measure	Rituximab Monotherapy n=156 Participants Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 Participants Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
Overall Survival	NA months Interval 3.6 to 98.9 Median OS had not been reached at time of analysis.	NA months Interval 3.4 to 97.8 Median OS had not been reached at time of analysis.

Adverse Events

Rituximab Monotherapy

Serious events: 13 serious events

Other events: 138 other events

Deaths: 0 deaths

Rituximab + IFN

Serious events: 34 serious events

Other events: 155 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Rituximab Monotherapy n=156 participants at risk Participants rituximab received 375 mg/m\^2, IV, once weekly for 4 weeks. Participants who achieved MR, PR, or CR after the first cycle received a second cycle of treatment for a maximum of 2 cycles.	Rituximab + IFN n=157 participants at risk Participants received rituximab 375 mg/m\^2, IV, once weekly for 4 weeks. Participants also received IFN-α2a 3 MIU/day, SC, during Week 1, and 4.5 MIU/day, SC, 6 days per week during Weeks 2 through 5. IFN-α2a was not administered on days of rituximab administration. Participants who achieved MR, PR, or CR during the first cycle received a second cycle of treatment for a maximum of 2 cycles.
General disorders General disorders and administration site conditions (ASC)	1.3% 2/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	5.7% 9/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Gastrointestinal disorders Gastrointestinal disorders	2.6% 4/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	3.8% 6/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Blood and lymphatic system disorders Blood and lymphatic system disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	3.8% 6/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal (T&M) disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	1.3% 2/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Infections and infestations Infections and infestations	1.9% 3/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	3.2% 5/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Nervous system disorders Nervous system disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	2.5% 4/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue (CT) disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	1.3% 2/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Immune system disorders Immune system disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Investigations Investigations	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Cardiac disorders Cardiac disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	1.3% 2/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Injury, poisoning and procedural complications Injury, poisoning and procedural complications (PC)	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	1.9% 3/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Metabolism and nutrition disorders Metabolism and nutrition disorders	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	1.3% 2/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Psychiatric disorders Psychiatric disorders	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Vascular disorders Vascular disorders	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.00% 0/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Ear and labyrinth disorders Ear and labyrinth disorders	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Eye disorders Eye disorders	0.00% 0/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.64% 1/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (including cysts)	0.64% 1/156 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).	0.00% 0/157 • Participants were assessed for adverse events (AEs) from BL, Weeks 1 through 16, and Months 6, 12, 18, 24, 30, and 42 of the follow-up period. Nonserious AEs presented in this record include all AEs reported during the study, not just nonserious events. Additionally, AE information is presented by system organ class (SOC) as AE data by preferred term were not available within the specified parameters (that is, with 5% threshold).