Andecaliximab as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Adults With Moderately to Severely Active Rheumatoid Arthritis

NCT02862574 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-373-14992016-000897-39
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

Brief Summary

The primary objective of this study is to evaluate the efficacy of andecaliximab (GS-5745) versus placebo as an add-on therapy to a tumor necrosis factor (TNF) inhibitor and methotrexate in adults with moderate to severe rheumatoid arthritis (RA).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Tumor Necrosis Factor Inhibitor; TNF-IR; Methotrexate

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in DAS28(CRP) at Week 12

  The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and 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 Outcomes (3)

• Percentage of Participants That Achieve DAS28(CRP) ≤ 3.2 at Week 12

  Week 12

• Percentage of Participants That Achieve DAS28(CRP) < 2.6 at Week 12

  Week 12

• Plasma Concentration of Andecaliximab

  Day 4 or 6 (± 1 day)

Study Arms (4)

Andecaliximab 300 mg

EXPERIMENTAL

Andecaliximab 300 mg for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate.

Drug: Andecaliximab; Drug: Methotrexate; Drug: TNF Inhibitor

Andecaliximab 150 mg

EXPERIMENTAL

Andecaliximab 150 mg + placebo for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate.

Drug: Andecaliximab; Drug: Placebo; Drug: Methotrexate; Drug: TNF Inhibitor

Placebo

PLACEBO COMPARATOR

Placebo weekly for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate.

Drug: Placebo; Drug: Methotrexate; Drug: TNF Inhibitor

Open-Label Extension

EXPERIMENTAL

On the Week 12 visit, eligible participants may choose to participate in the open-label portion of the study to receive open-label andecaliximab 300 mg for 52 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate.

Drug: Andecaliximab; Drug: Methotrexate; Drug: TNF Inhibitor

Interventions

Andecaliximab DRUG

Administered via subcutaneous injection once weekly

Also known as: GS-5745

Andecaliximab 150 mg; Andecaliximab 300 mg; Open-Label Extension

Placebo DRUG

Administered via subcutaneous injection once weekly

Andecaliximab 150 mg; Placebo

Methotrexate DRUG

Administered orally weekly as part of the participant's current treatment regimen

Andecaliximab 150 mg; Andecaliximab 300 mg; Open-Label Extension; Placebo

TNF Inhibitor DRUG

An approved stable subcutaneous formulation of one of the following TNF inhibitors may include adalimumab, certolizumab, etanercept, or golimumab.

Andecaliximab 150 mg; Andecaliximab 300 mg; Open-Label Extension; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA (according to the 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria) confirmed at screening
• Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to first dose of study drug
• Individuals on MTX may also be on concurrent chloroquine or hydroxychloroquine at a stable dose (defined as no change in prescription) for at least 4 week prior to Baseline; if so, they should plan to continue this medication for the duration of the study
• Must have an inadequate response to ≥ 12 weeks of ongoing treatment with an approved, stable subcutaneous (SC) formulation of TNF inhibitor (adalimumab, certolizumab pegol, etanercept, or golimumab), or marketed SC biosimilar TNF inhibitor with at least 6 weeks of stable dose (defined as no change in prescription), defined as: must have a DAS28(CRP) \> 3.2 at screening AND must have ≥ 3 swollen and ≥ 3 tender joints (using the DAS28 joint counts) at screening and at baseline (do not need to be the same joints)
• Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to baseline are allowed and throughout the blinded period of the study. PRN NSAID for indications other than RA are also allowed. (PRN means "pro re nata" or when necessary)
• Tuberculosis (TB) Screening: Must meet either a. or b.:
• A negative history of TB infection and a negative QuantiFERON® TB-Gold In-Tube test and chest x-ray results. (QuantiFERON® tests with inconclusive results may be repeated one time. If the repeat result is also inconclusive, the individual will be excluded from the study).
• OR,
• A negative chest x-ray (views per local guidelines) for active TB or other lung disease at screening; or a chest x-ray within 90 days of screening if films or report are available for investigator review

You may not qualify if:

• Current treatment with any other disease modifying anti-rheumatic drug (DMARD) other than MTX, chloroquine or hydroxychloroquine, OR current treatment with other immune modulating/suppressive non-biologic and biologic medications as described in the study protocol
• Intraarticular corticosteroid injection of any joint within 4 weeks of baseline
• Any infection requiring oral antimicrobial therapy within 2 weeks prior to baseline
• Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication (individuals with Sjogren's syndrome or controlled thyroiditis as defined by the investigator are not excluded)
• Active systemic involvement secondary to RA such as vasculitis or Felty's syndrome
• History of any of the following within 12 months of baseline:
• infection requiring parenteral antibiotics or hospitalization
• any life-threatening infection
• sepsis
• The results of the following laboratory tests performed at the central laboratory at screening meet any of the criteria below:
• Hemoglobin \< 8.0 g/dL (International System of Units (SI): \< 80 g/L)
• White blood cells \< 3.0 x 10\^3 cells/mm\^3 (SI: \< 3.0 x 10\^9 cells/L)
• Neutrophils \< 1.5 x 10\^3 cells/mm\^3 (SI: \< 1.5 x 10\^9 cells/L)
• Lymphocytes \< 0.5 x 10\^3 cells/mm\^3 (SI: \< 0.5 x 10\^9 cells/L)
• Platelets \< 100 x 10\^3 cells/mm\^3 (SI: \< 100 x 10\^9 cells/L)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (8)

Stanford University

Palo Alto, California, 94304, United States

Location

Omega Research Consultants, LLC

DeBary, Florida, 32713, United States

Location

G. Timothy Kelly, MD

Las Vegas, Nevada, 89128, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Albuquerque Center for Rheumatology

Albuquerque, New Mexico, 87102, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Tekton Research

Austin, Texas, 78728, United States

Location

Accurate Clinical Research

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

andecaliximab; Methotrexate; Tumor Necrosis Factor Inhibitors

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

Gilead decided to discontinue the development of andecaliximab in RA and this study was terminated. The decision was not due to any safety concerns. Because only 15 participants were enrolled, no formal statistical testing was completed.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: December 15, 2016
• Primary Completion: June 26, 2017
• Study Completion: August 7, 2017
• Last Updated: June 27, 2018
• Results First Posted: June 27, 2018

Record last verified: 2018-05

Locations

US (8)