GS-0272 for Rheumatoid Arthritis and Lupus

(MARASLE Trial)

Recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, GS-0272, to evaluate its safety and effectiveness for people with rheumatoid arthritis (RA). Researchers aim to understand how the body processes the drug and whether it causes any side effects over time. Participants will receive either GS-0272 or a placebo to compare results. The trial suits individuals who have lived with RA for at least three months and are already on certain RA medications, excluding biologics. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that GS-0272 is likely to be safe for humans?

Research shows that GS-0272 remains in the early stages of testing for rheumatoid arthritis (RA), so limited information exists about its safety in humans. Previous studies have examined how well people tolerate GS-0272 and whether any side effects occur. The available data does not provide detailed information about negative reactions or problems. Since GS-0272 is in a Phase 1 trial, researchers focus on assessing the drug's safety and determining the appropriate dose.

This phase often marks the first time a drug is administered to humans, so safety information is still being gathered. It is important to understand that this phase helps researchers learn how the body reacts to the drug, but it may not yet provide complete safety details. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about GS-0272 because it represents a new approach to treating rheumatoid arthritis (RA) and lupus. Unlike traditional treatments like methotrexate or biologics that primarily target inflammation or specific immune proteins, GS-0272 works by a unique mechanism of action that may offer more precise targeting of disease pathways. This specificity could potentially lead to fewer side effects and improved efficacy, making it a promising alternative for patients who have not responded well to existing therapies. The potential to tailor treatment more closely to individual patient needs is a key reason for the excitement surrounding GS-0272.

What evidence suggests that GS-0272 might be an effective treatment for rheumatoid arthritis?

Research has shown that GS-0272 may help people with lupus. In a study with 158 lupus patients, 109 experienced improvements after using the treatment. This trial will also evaluate GS-0272 for rheumatoid arthritis (RA). Participants will be randomized to receive either GS-0272 or a placebo. Although limited data exists on GS-0272's effectiveness for RA, these early findings are promising. The treatment targets inflammation, a key factor in both lupus and RA, suggesting it could be effective for RA as well. ^{1 3 4 6 7}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06031415

Study of GS-0272 in Participants With Rheumatoid Arthritis 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 ...

2. withpower.com withpower.com/trial/phase-1-arthritis-8-2023-48573

GS-0272 for Rheumatoid Arthritis and Lupus In a study of 158 patients with systemic lupus erythematosus, the SLEDAI-2K effectively identified 109 patients who showed overall improvement in disease ...

3. gileadclinicaltrials.com gileadclinicaltrials.com/study?nctid=NCT06031415

Study of GS-0272 in Participants With Rheumatoid Arthritis ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11979130/

Resolution of inflammation during rheumatoid arthritis - PMC Abatacept treatment significantly reduced the proportions of Tregs and PD-1+ TFh cells and is effective in clinical patients with RA (Aldridge et al., 2022).

5. med.stanford.edu med.stanford.edu/content/sm/sleepdivision/research/clinicaltrials/results.html?start=400

Clinical Trials results | Division of Sleep Medicine 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06031415

Study of GS-0272 in Participants With Rheumatoid Arthritis 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 ...

7. isrctn.com isrctn.com/ISRCTN11269259

A 2-part study to investigate the safety, tolerability and ... The results from each of the groups in Part A have been compared to determine if there are any significant differences in the safety profile of GS-0272, the ...