GS-0272 for Rheumatoid Arthritis and Lupus

(MARASLE Trial)

Recruiting at 16 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must be taking: CsDMARDs

Must not be taking: Biologics, tsDMARDs

Disqualifiers: Hepatitis, HIV, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

87 Participants Needed

Trial Summary

What is the purpose of this trial?

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). The primary objectives of this study are to assess the safety and tolerability of multiple ascending doses of GS-0272 and to characterize the pharmacokinetics of GS-0272 following multiple doses of GS-0272, in participants with RA.

Will I have to stop taking my current medications?

If you are taking biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs/tsDMARDs), you will need to stop them at least 4 weeks before starting the study drug, except for rituximab, which requires a 16-week break. However, you can continue taking 1 or 2 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) if your dose has been stable for at least 4 weeks before the study.

What data supports the effectiveness of the drug GS-0272 for treating rheumatoid arthritis and lupus?

The research on similar treatments, like anifrolumab and belimumab, shows that achieving a low disease activity state in lupus patients is linked to better outcomes, suggesting that drugs targeting similar pathways may be effective. Additionally, disease-modifying antirheumatic drugs (DMARDs) have shown significant improvement in rheumatoid arthritis patients compared to placebo, indicating potential effectiveness for GS-0272 if it works similarly. ^{1 2 3 4 5}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with Rheumatoid Arthritis (RA) or Systemic Lupus Erythematosus (SLE). RA patients must have been diagnosed at least 3 months ago and on stable csDMARDs, not b/tsDMARDs. SLE patients need a diagnosis from at least 24 weeks prior and stable nonbiologic treatments. Those with certain infections or highly active SLE are excluded.

Inclusion Criteria

I am not taking specific arthritis drugs and haven't for the last 4 weeks (or 16 weeks for rituximab).

I have been on a stable dose of my lupus medication for at least 4 weeks.

I have been on 1 or 2 arthritis medications for at least 12 weeks, with a stable dose for the last 4 weeks.

Exclusion Criteria

I haven't taken lupus medication or cyclophosphamide in the last 8 weeks.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Meet any of the protocol-specified infection criteria (hepatitis C, Hepatitis B, HIV, tuberculosis, others).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either GS-0272 or placebo for 12 weeks in multiple ascending doses

12 weeks

Regular visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Treatment Details

Interventions

• GS-0272

Trial Overview The study tests GS-0272's safety and how the body processes it after multiple doses in RA and SLE patients. Participants will receive either GS-0272 or a placebo through subcutaneous injections to compare effects.

Participant Groups

Group I: Part B: Active RA Cohort: GS-0272 or Placebo Experimental Treatment 2 Interventions

Part B will include participants with moderate-to-severe RA. Part B will have only 1 cohort (Cohort 4). Participants in Cohort 4 will be randomized in a 2:1 ratio to receive either GS-0272 or placebo for 12 weeks.

Group II: Part A: Rheumatoid Arthritis (RA) Cohorts: GS-0272 or Placebo Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

In a study of 158 patients with systemic lupus erythematosus, the SLEDAI-2K effectively identified 109 patients who showed overall improvement in disease activity without significant worsening in other areas.

Among the improved patients, only 11 had new laboratory descriptors that were not clinically significant, indicating that the SLEDAI-2K is reliable for assessing true improvements in disease status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement. Touma, Z., Gladman, DD., Su, J., et al.[2015]

In a post hoc analysis of two phase 3 trials involving 819 patients with systemic lupus erythematosus (SLE), anifrolumab treatment led to a significantly higher rate of achieving lupus low disease activity state (LLDAS) at week 52 compared to placebo (30.0% vs 19.6%).

Anifrolumab was associated with earlier attainment of LLDAS, increased cumulative time in LLDAS, and higher rates of sustained LLDAS, indicating its efficacy in improving disease management in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus. Morand, EF., Abreu, G., Furie, RA., et al.[2023]

In a post-hoc analysis of 1684 SLE patients from two clinical trials, the clinical SLE disease activity index 2000 (cSLEDAI-2K) zero was found to be the most effective outcome measure, showing a strong correlation with physician assessments of disease activity.

Belimumab at 10 mg/kg demonstrated significant superiority over placebo in achieving cSLEDAI-2K = 0, indicating its efficacy in treating systemic lupus erythematosus, while the Lupus Low Disease Activity State (LLDAS) was a more stringent and less frequently achieved measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies. Parodis, I., Emamikia, S., Gomez, A., et al.[2021]

In a Phase IIb trial involving 305 patients with systemic lupus erythematosus (SLE), anifrolumab treatment led to a higher rate of achieving the Lupus Low Disease Activity State (LLDAS) compared to placebo, indicating its efficacy in managing SLE symptoms.

The study found that anifrolumab-treated patients not only reached LLDAS earlier but also spent more time in this state, supporting the use of LLDAS as a meaningful endpoint in SLE clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. Morand, EF., Trasieva, T., Berglind, A., et al.[2019]

A new composite index was created to measure improvement in rheumatoid arthritis (RA) patients during trials of disease-modifying antirheumatic drugs (DMARDs), based on data from 130 placebo-treated participants.

The index showed that very few patients on placebo improved, while significantly more patients receiving DMARDs demonstrated improvement, suggesting the index could help predict patient responses in future RA trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. The Cooperative Systematic Studies of Rheumatic Diseases Group. Paulus, HE., Egger, MJ., Ward, JR., et al.[2022]

References

1. Canada pubmed.ncbi.nlm.nih.gov

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Lupus low disease activity state attainment in the phase 3 TULIP trials of anifrolumab in active systemic lupus erythematosus. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Analysis of improvement in individual rheumatoid arthritis patients treated with disease-modifying antirheumatic drugs, based on the findings in patients treated with placebo. The Cooperative Systematic Studies of Rheumatic Diseases Group. [2022]