A Long Term Safety Study of Mavrilimumab in Adult Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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A clinical study to investigate the safety of mavrilimumab, an antibody being developed for the treatment of moderate to severe rheumatoid arthritis, an inflammatory condition that affects the joints.

Detailed Description
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Despite the therapeutic improvements with recent biologic agents approved for rheumatoid arthritis (RA), there is still a significant unmet medical need for the treatment of subjects with this chronic disease to achieve a faster, more complete response, and higher rates of remission. This study is an open-label extension study for subjects who have participated in one of the qualifying development program studies with mavrilimumab. Participation in this study will allow these subjects to continue to receive long-term treatment with mavrilimumab. The data from this study will provide an evaluation of the long-term safety of mavrilimumab in adult subjects with RA. In addition, long-term exploratory efficacy outcomes such as joint damage and disability will be evaluated.

Official Title
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An Open-label Extension Study to Evaluate the Long-term Safety of Mavrilimumab in Adult Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Mavrilimumab 100 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have completed the treatment period of the qualifying study or will have failed to respond adequately to investigational product at a predefined time point in the qualifying study regardless of their initial randomization. No evidence of clinically uncontrolled respiratory disease to be confirmed by a local pulmonologist Exclusion Criteria: Subjects who have been permanently discontinued from investigational product in previous qualifying study. Any new conditions or worsening of any pre-existing conditions as defined in the protocol.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavrilimumab 100 mg<br>Participants will receive 100 mg mavrilimumab once in every 2 weeks (Q2W) subcutaneously for up to 3 years. | Biological: Mavrilimumab 100 mg<br>* Participants will receive 100 mg mavrilimumab once in every 2 weeks (Q2W) subcutaneously for up to 3 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg. | From the start of study drug administration up to 12 weeks after the last dose of study drug (approximately up to 3 years) | 
| Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Laboratory parameters included hematology, serum chemistry and urinalysis recorded as TEAEs. Clinical laboratory abnormalities recorded as TEAEs were reported.TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg. | From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years) | 
| Number of Participants With Vital Sign Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs) | Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiration rate. Vital sign abnormalities recorded as TEAEs were reported. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg. | From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years) | 
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs | The 12-lead ECG data were summarized and evaluated. TEAEs related to abnormal ECG findings were recorded and reported. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg. | From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years) | 
| Number of Participants With Forced Expiratory Volume in 1 Second (FEV1) Outside Threshold Values | Pulmonary function testing was performed by spirometry to assess forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.The percentage (%) of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as less than or equal to (=<)15% reduction from baseline, greater than (>)15% to =<20% reduction from baseline, >20% reduction from baseline and >20% reduction to <80%. The threshold values refer to baseline values for each participant. | From Week 24 to Week 130 at specified time points | 
| Number of Participants With Forced Expiratory Volume in 6 Seconds (FEV6) Outside Threshold Values | Pulmonary function testing was performed by spirometry to assess forced expiratory volume in 6 seconds (FEV6). FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. The percentage of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as =<15% reduction from baseline, >15% to =<20% reduction from baseline, >20% reduction from baseline and >20% reduction to <80%. The threshold values refer to baseline values for each participant. | From Week 24 to Week 130 at specified time points | 
| Number of Participants With Forced Vital Capacity (FVC) Outside Threshold Values | Pulmonary function testing was performed by spirometry to assess forced vital capacity (FVC). FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The percentage of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as =<15% reduction from baseline, >15% to =<20% reduction from baseline, >20% reduction from baseline and >20% reduction to <80%. The threshold values refer to baseline values for each participant. | From Week 24 to Week 156 at specified time points | 
| Number of Participants With Clinically Meaningful Change in Borg Dyspnea Score Considered as an AE | Borg dyspnea score was a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The score ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicated greater difficulty in breathing. | From Week 0 to Week 132 at specified time points | 
| Oxygen Saturation Levels by Pulse Oximetry | Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. | From Week 0 to Week 132 at specified time points | 
| Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | DLCO is a pulmonary function testing that measures partial pressure difference between inspired and expired carbon monoxide. | From Week 12 to Week 156 at specified time points |