Clinical trial NCT04577781: 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
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of GLPG3970, Administered Orally for 6 Weeks in Adult Subjects With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Arthritis
Rheumatic Diseases
Moderately active rheumatoid arthritis
Severely active rheumatoid arthritis
Joint Diseases
Autoimmune Diseases
Musculoskeletal Diseases
Musculoskeletal and connective tissue disorders
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in DAS-28 (CRP) at Week 6
timeFrame: Baseline and Week 6
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From first dose of study drug until end of the study (up to 8 weeks)
measure: Plasma Concentration (Ctrough) of GLPG3970
timeFrame: Day 15: pre-dose; Day 29: pre-dose; Day 43: pre-dose
Other outcomes:
Locations:
city: Ruse
country: Bulgaria
facility: Medical Center Teodora
city: Sofia
country: Bulgaria
facility: UMHAT Sv. Ivan Rilski EAD
city: Tbilisi
country: Georgia
facility: Aversi Clinic Ltd
city: Tbilisi
country: Georgia
facility: Consilium Medulla-multiprofile clinic Ltd
city: Poznan
country: Poland
facility: Centrum Medyczne Grunwald
city: Poznań
country: Poland
facility: Centrum Badan Klinicznych S.C.
city: Kharkiv
country: Ukraine
facility: GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
city: Vinnytsia
country: Ukraine
facility: SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU
city: Zaporizhzhya
country: Ukraine
facility: Medical Center Clinic of Modern Rheumatology
Study officials:
affiliation: Galapagos NV
name: Galapagos Medical Director
role: STUDY_DIRECTOR
References: