A Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 6 Weeks in Adults With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: GLPG3970; Placebo
Intervention description: GLPG3970 powder and solvent for oral solution to be reconstituted prior to use.; Placebo powder and solvent for oral solution to be reconstituted prior to use.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Arthritis; Rheumatic Diseases; Moderately active rheumatoid arthritis; Severely active rheumatoid arthritis; Joint Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Musculoskeletal and connective tissue disorders

Summary:

      The primary objective of this study was to evaluate the effect of GLPG3970 compared to
      placebo on the signs and symptoms of Rheumatoid Arthritis (RA) in participants with
      moderately to severely active RA and an inadequate response to methotrexate (MTX).
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. A body mass index (BMI) between 18-32 kg/m^2, inclusive.

          2. Diagnosis of RA ≥6 months prior to screening AND meeting the 2010 American College of
             Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria of RA AND ACR
             functional class I-III.

          3. Have ≥6 swollen joints (from a swollen joint count evaluated in 66 joints [SJC66]) AND
             ≥8 tender joints (from a tender joint count evaluated in 68 joints [TJC68]) at
             screening and at the baseline visit (Visit 1) prior to the first investigational
             product (IP) dosing.

          4. DAS28 (CRP) >3.2 (moderate disease) at screening.

          5. Screening serum high sensitivity C-reactive protein (hsCRP) > upper limit of normal
             (ULN, central laboratory reference: ≤ 5.0 mg/L).

          6. Inadequate response to MTX, i.e. treatment-experienced participants who demonstrated
             inadequate clinical response during treatment with MTX.

          7. Have received MTX for ≥6 months and on stable dose (10 to 20 mg/week) of MTX for at
             least 4 weeks prior to screening and willing to continue on their current stable dose
             and dosing regimen for the duration of the study.

          8. If taking systemic steroids, prednisone equivalent at a dose of ≤10 mg/day and stable
             for at least 4 weeks prior to the first IP dosing.

        Key Exclusion Criteria:

          1. Current therapy with any conventional disease-modifying antirheumatic drug (DMARD)
             other than MTX, including

               1. oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or
                  D-penicillamine within 4 weeks prior to screening,

               2. cyclosporine within 8 weeks prior to screening, and

               3. leflunomide within 3 months prior to screening or a minimum 4 weeks prior to
                  screening if after 11 days of standard cholestyramine therapy.

          2. Current or previous treatment with a biologic DMARD (bDMARD). Except for participants
             who received bDMARDs only in a single clinical study setting:

               1. For whom the last dose of bDMARD ≥6 months prior to screening (12 months for
                  rituximab or other lymphocyte depleting agents), AND;

               2. For whom the bDMARD was effective, without being discontinued due to lack of
                  efficacy.

          3. Participants who received an intra-articular or parenteral corticosteroid injection
             within 4 weeks prior to screening.

          4. Participants who received a prior surgical intervention within 12 weeks prior to
             screening or likely requirement for surgery during the study.

          5. Participant has a history of tuberculosis (TB) diagnosis or evidence of active or
             latent infection with Mycobacterium tuberculosis as defined by one of the following
             assessments:

               1. Positive QuantiFERON-TB Gold test result at screening, OR

               2. Chest radiograph (posterior anterior view) taken within 12 weeks prior to
                  screening, read by a qualified radiologist or pulmonologist, with evidence of
                  current active TB or old inactive TB.

          6. Participant has any active systemic infection within the last 2 weeks prior to first
             IP dosing, or poorly controlled chronic cardiac, pulmonary or renal disease.

          7. Participant has a known or suspected history of or a current immunosuppressive
             condition, or a history of invasive opportunistic infections (e.g. human
             immunodeficiency virus [HIV] infection, histoplasmosis, listeriosis, coccidiodmycosis,
             pneumocystosis, aspergillosis).

          8. Participant has a chronic hepatitis B virus (HBV) infection, as defined by persistent
             HBV surface antigen (HBsAg) positivity. Participant has hepatitis C virus (HCV)
             infection, as defined by positive HCV antibody at screening and detectable HCV
             viremia. Participants with positive HCV antibody must undergo reflex HCV ribonucleic
             acid (RNA) testing, and participants with HCV RNA positivity will be excluded.
             Participants with positive HCV antibody and negative HCV RNA are eligible.

          9. Participant testing positive at screening for severe acute respiratory syndrome
             coronavirus 2 (SARS-CoV-2) infection as detected by real time polymerase chain
             reaction (RT-PCR), participants presenting any signs or symptoms as detected at
             baseline following careful physical examination (e.g. cough, fever, headaches,
             fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, others) or
             reporting any signs and symptoms for the 2 preceding weeks, or participants who have
             been exposed to individuals with confirmed or suspected diagnosis of SARS-CoV-2 within
             2 weeks prior to baseline. In addition, any other locally applicable standard
             diagnostic criteria may also apply to rule out SARS-CoV-2 infection.

        Note: Other protocol-defined Inclusion/Exclusion criteria may apply.