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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02862574
• Date of registration: 08/08/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences
• Public title: Andecaliximab as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Adults With Moderately to Severely Active Rheumatoid Arthritis
• Scientific title: Evaluation of the Efficacy and Safety of GS-5745 as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Subjects With Moderate to Severe Rheumatoid Arthritis
• Date of first enrolment: December 15, 2016
• Target sample size: 15
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02862574
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Australia, Hungary, Taiwan, United States

Contacts

• Name: Gilead Study Director
• Affiliation: Gilead Sciences

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- 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.:

1. 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,

2. Individuals with a history of latent TB treated with a full course of prophylaxis
as per local guidelines are allowed per investigator judgment. It is the
responsibility of the investigator to verify the adequacy of previous treatment
and to provide appropriate documentation. In these cases, no QuantiFERON® test
need be obtained. In addition, these cases must be approved by the medical
monitor prior to enrollment. (Any new diagnosis of latent TB or prior untreated
/partially treated latent TB in NOT allowed (ie, individuals who require
prophylactic therapy for TB during the study). Any prior history of active TB
[regardless of treatment] is exclusionary).

- 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

Key Exclusion Criteria:

- 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)

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2 x upper
limit of normal (ULN)

- Total bilirubin level = 2 x ULN unless the individual has been diagnosed with
Gilbert's disease and this is clearly documented

- Estimated glomerular filtration rate < 40 mL/min/1.73 m^2 based on the
Modification of Diet in Renal Disease (MDRD) formula

- Positive HIV serology during screening

- Evidence of active Hepatitis B Virus (HBV) infection

- Evidence of active Hepatitis C Virus (HCV) infection

- Any uncontrolled clinically significant laboratory abnormality that would affect
interpretation of study data or the individual's participation in the study

- Malignancy or a history of malignancy or lymphoproliferative disorder within 10 years
of screening with the following exceptions:

- Carcinoma in situ of the cervix that has been successfully treated

- Adequately treated basal or squamous cell cancer that has been successfully
treated

Note: Other protocol defined inclusion/exclusion criteria may apply.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Methotrexate

Drug: TNF Inhibitor

Drug: Andecaliximab

Drug: Placebo

Primary Outcome(s)

Change From Baseline in DAS28(CRP) at Week 12 [Time Frame: Baseline; Week 12]

Secondary Outcome(s)

Percentage of Participants That Achieve DAS28(CRP) < 2.6 at Week 12 [Time Frame: Week 12]

Percentage of Participants That Achieve DAS28(CRP) = 3.2 at Week 12 [Time Frame: Week 12]

Plasma Concentration of Andecaliximab [Time Frame: Day 4 or 6 (± 1 day)]

Secondary ID(s)

GS-US-373-1499

2016-000897-39

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02862574