Safety, Tolerability, and Efficacy of GS-9876 in Participants With Active Rheumatoid Arthritis on Background Therapy With Methotrexate

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Proof-of-Concept Study to Evaluate Safety, Tolerability, and Efficacy of GS-9876 in Subjects With Active Rheumatoid Arthritis on Background Therapy With Methotrexate

The primary objective of this study is to evaluate the effect of GS-9876 versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) in participants with active RA as measured by change from baseline in Disease Activity Score for 28 joint count using C-reactive protein (CRP) (DAS28 (CRP)) at Week 12.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: GS-9876; Drug: Filgotinib placebo; Drug: Methotrexate; Drug: Filgotinib; Drug: GS-9876 placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • MHAT-Plovdiv AD
  • Plovdiv, Bulgaria, 4003
    • UMHAT Kaspela
  • Sofia, Bulgaria, 1233
    • NMTH Tsar Boris III
• Czechia
  • Plzen, Czechia, 31200
    • A-Shine s.r.o.
  • Uherske Hradiste, Czechia, 68601
    • Medical Plus, S.R.O.
• Georgia
  • T'bilisi, Georgia, 0112
    • LLC Arensia Exploratory Medicine
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • ARENSIA Exploratory Medicine Phase I Unit, Republican Clinical Hospital
• Poland
  • Bialystok, Poland, 15-879
    • ClinicMed Badurski i Wspolnicy Spolka Jawna
• Ukraine
  • Kharkiv, Ukraine, 140176
    • Kharkiv City Hospital 8
  • Kyiv, Ukraine, 2068
    • Medical Center_Clinic of International Institute of clinical Studies
• United States
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
  • Georgia
    • Canton, Georgia, United States, 30114
      • Medical Associates of North Georgia
  • Kentucky
    • Elizabethtown, Kentucky, United States, 42701
      • Center for Arthritis and Osteoporosis
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Center for Rheumatology
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Houston, Texas, United States, 77084
      • Accurate Clinical Management - Najam
    • Stafford, Texas, United States, 77477
      • Accurate Clinical Research Inc.
    • Webster, Texas, United States, 77598
      • Medical Center Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Active RA disease as defined by: a tender joint count (TJC) of ≥ 6 (out of 68), a swollen joint count (SJC) of ≥ 6 (out of 66) at screening and Day 1
• Inadequate response to treatment with oral or parenteral methotrexate (MTX) 7.5 to 25 mg/week continuously for at least 12 weeks
• No evidence of active or latent tuberculosis

Key Exclusion Criteria:

• Prior treatment with B-cell depleting agents (eg, rituximab), unless more than 6 months prior to the first dose of study drug and documented return of CD19+ cells at screening
• Prior treatment with any commercially available or investigational spleen tyrosine kinase (SYK) inhibitor
• Concurrent treatment with any other conventional synthetic DMARD (csDMARD) other than MTX and/or hydroxychloroquine (HCQ) (prior csDMARD treatment allowed if appropriate wash out as defined in the protocol)
• Concurrent treatment with any biological disease modifying anti-rheumatic drug (bDMARD)(prior bDMARD treatment allowed if appropriate wash out as defined in the protocol). Prior failure to treatment with bDMARDs is not an exclusion criterion.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GS-9876 - 30 mg; GS-9876 30 mg + filgotinib placebo for 12 weeks	Drug: GS-9876; One tablet administered orally once daily; Drug: Filgotinib placebo; Two tablets administered orally once daily; Drug: Methotrexate; Background therapy with methotrexate administered orally or parenterally once weekly
Experimental: GS-9876 - 10 mg; GS-9876 10 mg + filgotinib placebo for 12 weeks	Drug: GS-9876; One tablet administered orally once daily; Drug: Filgotinib placebo; Two tablets administered orally once daily; Drug: Methotrexate; Background therapy with methotrexate administered orally or parenterally once weekly
Experimental: Filgotinib; Filgotinib + GS-9876 placebo for 12 weeks	Drug: Methotrexate; Background therapy with methotrexate administered orally or parenterally once weekly; Drug: Filgotinib; Two tablets administered orally once daily; Drug: GS-9876 placebo; One tablet administered orally once daily
Placebo Comparator: Placebo; GS-9876 placebo + filgotinib placebo for 12 weeks	Drug: Filgotinib placebo; Two tablets administered orally once daily; Drug: Methotrexate; Background therapy with methotrexate administered orally or parenterally once weekly; Drug: GS-9876 placebo; One tablet administered orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) at Week 12	Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), participant's global assessment of disease activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity) and C-Reactive Protein (CRP) for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.	Baseline; Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved American College of Rheumatology (ACR)20 Improvement at Week 12	American College of Rheumatology (ACR)20 response was defined as having ≥ 20% improvement from baseline in the number of tender and the number of swollen joints, and a 20% improvement in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity (PhGA), Participant's Global Assessment of Disease Activity (PtGA), Participant's pain assessment, Participant's assessment of physical function (HAQ-DI) score, and C-reactive protein (CRP).	Week 12
Percentage of Participants Who Achieved ACR50 Improvement at Week 12	ACR50 response was defined as having ≥ 50% improvement from baseline in the number of tender and the number of swollen joints, and a 50% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP.	Week 12
Percentage of Participants Who Achieved ACR70 Improvement at Week 12	ACR70 response was defined as having ≥ 70% improvement from baseline in the number of tender and the number of swollen joints, and a 70% improvement in at least 3 of the following 5 criteria: PhGA, PtGA, Participant's pain assessment, HAQ-DI score, and CRP.	Week 12
Change From Baseline in The Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 12	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a self-reported tool used to assess the ability to perform tasks in 8 functional categories: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and common daily activities. Responses in each functional category were collected as 0 (without any difficulty) to 3 (unable to do a task in that area). The HAQ-DI score ranges from 0 (no disability) to 3 (completely disabled), when 6 or more categories are non-missing.	Baseline; Week 12

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2016
• Primary Completion (Actual): August 22, 2017
• Study Completion (Actual): September 20, 2017

Study Registration Dates

• First Submitted: August 26, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 31, 2016

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: August 21, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: GS-US-379-1582; 2016-001496-75 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No