Study of GS-0272 in Participants With Rheumatoid Arthritis or Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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The goals of this clinical study are to learn more about the study drug, GS-0272, and its safety and tolerability following multiple doses in participants with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The primary objectives of this study are to assess the safety and tolerability of multiple ascending subcutaneous (SC) doses of GS-0272 and to characterize the pharmacokinetics of GS-0272 following multiple SC doses of GS-0272, in participants with RA or SLE.

Official Title
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A Multicenter, Randomized, Placebo-Controlled Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Multiple Ascending Subcutaneous Doses of GS-0272 in Adult Participants With Rheumatoid Arthritis or Systemic Lupus Erythematosus (MARASLE)

Conditions
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Rheumatoid Arthritis, Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: GS-0272
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Part A (Rheumatoid Arthritis (RA) Cohorts)-Specific Inclusion Criteria: Diagnosis of RA at least 3 months prior to screening fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. Ongoing treatment with 1 or 2 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for at least 12 weeks prior to the first dose of study drug, with a stable dose for at least 4 weeks prior to the first dose of study drug, as follows: Individuals must not be on a biologic disease-modifying antirheumatic drugs (bDMARD)/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) at Day 1 or during the study and must discontinue b/tsDMARD use for at least 4 weeks (with the exception of rituximab, which must be discontinued for at least 16 weeks) prior to the first dose of study drug. Part B (Systemic Lupus Erythematosus (SLE) Cohort)-Specific Inclusion Criteria: Fulfill EULAR/ACR 2019 classification criteria for SLE at least 24 weeks prior to the first dose of study drug. Individuals using protocol-permitted nonbiologic immunosuppressive/immunomodulatory agents (antimalarials, methotrexate (MTX), azathioprine, cyclosporine, leflunomide, minocycline, mycophenolate mofetil, mycophenolic acid, dapsone, and oral [not topical] tacrolimus) for the treatment of SLE must maintain stable dose(s) for at least 4 weeks prior to the first dose of study drug and through the end of study. Key Exclusion Criteria: Meet any of the protocol-specified infection criteria (hepatitis C, Hepatitis B, HIV, tuberculosis, others). Highly active SLE (including but not limited to lupus nephritis (with significant increases in urine protein/creatinine ratio over clinical baseline, recent worsening or creatinine clearance, and/or pyuria/hematuria), neuropsychiatric SLE, and/or vasculitis) that could put the individual at risk per investigator's judgment. Exposure to cyclophosphamide or any biologic lupus therapy within 8 weeks prior to the first dose of study drug. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part A will have sequential cohorts. Part A and Part B will be in parallel.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Rheumatoid Arthritis (RA) Cohorts: GS-0272 or Placebo<br>Part A will include participants with RA. Part A will have 3 cohorts. Each cohort in Part A will be randomized in a 3:1 ratio to receive either ascending doses of GS-0272 or placebo for 12 weeks. Dosing will begin in Cohort 1. Cohorts 2 and 3 will be initiated upon review of blinded safety data from the preceding cohort. | Drug: GS-0272<br>* Administered subcutaneously<br>Drug: Placebo<br>* Administered subcutaneously<br>|
| Experimental: Part B: Systemic Lupus Erythematosus (SLE) Cohort: GS-0272 or Placebo<br>Part B will include participants with SLE. Part B will have only 1 cohort (Cohort 4). Participants in Cohort 4 will be randomized in a 3:1 ratio to receive either GS-0272 or placebo for 12 weeks. | Drug: GS-0272<br>* Administered subcutaneously<br>Drug: Placebo<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Adverse Events (AEs) |  | First dose up to Week 12 plus 70 days | 
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) |  | First dose up to Week 12 plus 70 days | 
| Percentage of Participants With Laboratory Abnormalities |  | First dose up to Week 12 plus 70 days | 
| Pharmacokinetics (PK) of GS-0272: AUCtau | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. | Day 1 predose through Day 197 | 
| PK of GS-0272: Cmax | Cmax is defined the maximum observed plasma drug concentration. | Day 1 predose through Day 197 | 
| PK of GS-0272: Tmax | Tmax is defined as the time to maximum observed concentration. | Day 1 predose through Day 197 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Antidrug Antibodies (ADAs) for GS-0272 | Prevalence of ADAs will be measured as the proportion of participants who had at least one positive ADA sample (baseline or post-baseline) among all participants evaluable for ADA prevalence. | Baseline (Day 1) through Day 197 | 
| Incidence of ADAs for GS-0272 | ADA incidence will be measured as the proportion of participants who have treatment-emergent ADA sample (post-baseline) among all participants evaluable for ADA incidence. | Baseline (Day 1) through Day 197 |