Trial Outcomes & Findings for KPL-301 for Subjects With Giant Cell Arteritis (NCT NCT03827018)

Last Updated: 2023-10-23

Results Overview

Time to flare by Week 26 was defined as time from randomization to the date of first flare occurring within the 26-week period, as assessed by independent adjudication. Kaplan-Meier method used to estimate the survival functions for each treatment arm. Flare/relapse was defined as a C-reactive protein (CRP) of 1 mg/dL or greater and/or erythrocyte sedimentation rate (ESR) of 30 mm/h or greater AND at least one of the following signs or symptoms attributed to GCA: Cranial symptoms (new-onset localized headache; scalp or temporal artery tenderness; ischemic-related vision loss; unexplained mouth or jaw pain upon mastication; transient ischemic attack or stroke related to GCA); Extracranial symptoms (claudication of the extremities; symptoms of polymyalgia rheumatica); New or worsening angiographic abnormalities detected via MRI, CT/CTA, or PET-CT of the aorta or other great vessels or via ultrasound of the temporal arteries.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

70 participants

Primary outcome timeframe

Week 26

Results posted on

2023-10-23

Participant Flow

Participant milestones

Participant milestones
Measure	Mavrilimumab Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Overall Study STARTED	42	28
Overall Study Completed Treatment	31	12
Overall Study COMPLETED	39	25
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Mavrilimumab Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	2	2
Overall Study Lack of Efficacy	0	1

Baseline Characteristics

KPL-301 for Subjects With Giant Cell Arteritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Total n=70 Participants Total of all reporting groups
Age, Continuous	69.7 years STANDARD_DEVIATION 6.98 • n=5 Participants	69.7 years STANDARD_DEVIATION 8.31 • n=7 Participants	69.7 years STANDARD_DEVIATION 7.48 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	18 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized White	40 Participants n=5 Participants	28 Participants n=7 Participants	68 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	41 Participants n=5 Participants	26 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: Modified Intent to Treat (mITT) Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Time to Flare by Week 26	NA weeks Not estimable per Kaplan-Meier method (insufficient number of subjects with events)	25.1 weeks Interval 16.0 to Not estimable per Kaplan-Meier method (insufficient number of subjects with events)

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

The sustained remission rate at Week 26 is defined as the percentage of participants with sustained remission, as assessed by independent adjudication, at Week 26, derived from the time to flare curve. Kaplan-Meier Survival Estimates with standard error and 95% CI for each arm. Participants who completed the treatment period without a flare by Week 26 were considered to have sustained remission.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Sustained Remission Rate at Week 26	83.2 percentage of participants Interval 67.9 to 91.6	49.9 percentage of participants Interval 29.6 to 67.3

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period. Participants with elevated ESR within 3 days of first dose are excluded from the analysis.

Elevated ESR is defined as first occurrence of ESR value ≥ 30 mm/hr. Participants with elevated ESR within 3 days of first dose are excluded from the analysis. Kaplan-Meier method used to estimate the survival functions for each treatment arm.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=40 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26	26.1 weeks Interval 16.1 to Not estimable per Kaplan-Meier method (insufficient number of subjects with events)	12.1 weeks Interval 8.1 to 16.6

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period. Participants with elevated CRP within 3 days of first dose are excluded from the analysis.

Elevated CRP is defined as first occurrence of CRP value ≥ 1.0 mg/dL. Participants with elevated CRP within 3 days of first dose are excluded from the analysis. Kaplan-Meier method used to estimate the survival functions for each treatment arm.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=39 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=27 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Time to Elevated C-Reactive Protein (CRP) by Week 26	NA weeks Interval 8.1 to Not estimable per Kaplan-Meier method (insufficient number of subjects with events)	12.3 weeks Interval 3.3 to 24.1

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Kaplan-Meier method used to estimate the survival functions for each treatment arm.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Time to Signs/Symptoms of Giant Cell Arteritis (GCA) or New or Worsening Vasculitis on Imaging by Week 26	NA weeks Not estimable per Kaplan-Meier method (insufficient number of subjects with events)	25.1 weeks Interval 15.1 to Not estimable per Kaplan-Meier method (insufficient number of subjects with events)

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Cumulative Corticosteroid Dose at Week 26	2074.15 mg Standard Deviation 708.433	2402.98 mg Standard Deviation 1014.446

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Participants were considered to have completed the corticosteroid taper if by week 26 receiving 1 mg/day for those who start with 60 mg/day, or 0 mg/day for those who start with doses \< 60 mg/day. 95% CI calculated using Clopper-Pearson confidence intervals.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal ESR	45.2 percentage of participants Interval 29.8 to 61.3	14.3 percentage of participants Interval 4.0 to 32.7

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level	23.8 percentage of participants Interval 12.1 to 39.5	14.3 percentage of participants Interval 4.0 to 32.7

SECONDARY outcome

Timeframe: Week 26

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Percentage of Participants Who Completed the 26-week Corticosteroid Taper and Who Had No Signs or Symptoms of GCA Nor New or Worsening Vasculitis by Imaging by Week 26	71.4 percentage of participants Interval 55.4 to 84.3	32.1 percentage of participants Interval 15.9 to 52.4

SECONDARY outcome

Timeframe: Final Safety Follow-up visit (Week 38)

Population: mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Mavrilimumab n=42 Participants Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 Participants Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period	2464.93 mg Standard Deviation 1106.636	2845.45 mg Standard Deviation 1320.115

Adverse Events

Mavrilimumab

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mavrilimumab n=42 participants at risk Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 participants at risk Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Congenital, familial and genetic disorders Hypertrophic cardiomyopathy	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	0.00% 0/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	3.6% 1/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
General disorders Oedema peripheral	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	3.6% 1/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Nervous system disorders Dementia	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	0.00% 0/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	3.6% 1/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38

Other adverse events

Additional Information

Clinical Operations Study Director

Kiniksa Pharmaceuticals (UK), Ltd. c/o Kiniksa Pharmaceuticals Corp.

Phone: 1-781-431-9100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the sole and exclusive right to publish information obtained from the trial. PI has no right to publish. PI may be invited to publish.
Publication restrictions are in place

Restriction type: OTHER

Measure	Mavrilimumab n=42 participants at risk Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Placebo n=28 participants at risk Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
Gastrointestinal disorders Constipation	7.1% 3/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	0.00% 0/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Gastrointestinal disorders Diarrhea	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	10.7% 3/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Gastrointestinal disorders Vomiting	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
General disorders Oedema peripheral	4.8% 2/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
General disorders Pyrexia	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Infections and infestations Nasopharyngitis	11.9% 5/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	10.7% 3/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Infections and infestations Oral herpes	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Infections and infestations Respiratory tract infection	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Infections and infestations Rhinitis	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Infections and infestations Upper respiratory tract infection	7.1% 3/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Injury, poisoning and procedural complications Fall	4.8% 2/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	17.9% 5/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Investigations Carbon monoxide diffusing capacity decreased	9.5% 4/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	3.6% 1/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Metabolism and nutrition disorders Diabetes mellitus	4.8% 2/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 2/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	14.3% 4/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Back pain	7.1% 3/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	10.7% 3/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 3/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	10.7% 3/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Neck pain	9.5% 4/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Osteoarthritis	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Musculoskeletal and connective tissue disorders Tendonitis	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Nervous system disorders Headache	14.3% 6/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	25.0% 7/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Nervous system disorders Hypoaesthesia	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Psychiatric disorders Sleep disorder	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	7.1% 2/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38
Vascular disorders Hypertension	2.4% 1/42 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38	14.3% 4/28 • All-Cause Mortality: From signing of informed consent (up to 6 weeks prior to Baseline) through Final Safety Follow-up / Week 38 Adverse Events: from first dose of study drug through Final Safety Follow-up / Week 38