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 (LADYBUG)

• ClinicalTrials.gov Identifier: NCT04577781
• Recruitment Status: Completed
• First Posted: October 8, 2020
• Last Update Posted: July 1, 2021
• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Study Description

Brief Summary:

The primary objective of this study is 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).

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: GLPG3970; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 12, 2020
• Actual Primary Completion Date: March 26, 2021
• Actual Study Completion Date: April 7, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: GLPG3970; Participants will receive GLPG3970 solution, orally, once daily for 6 weeks.	Drug: GLPG3970; GLPG3970 powder and solvent for oral solution to be reconstituted prior to use.
Placebo Comparator: Placebo; Participants will receive placebo solution, orally, once daily for 6 weeks.	Drug: Placebo; Placebo powder and solvent for oral solution to be reconstituted prior to use.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) (C-reactive protein [CRP]) at Week 6 [ Time Frame: Baseline and Week 6 ]

Secondary Outcome Measures :

1. Incidence of Treatment-emergent Adverse Events (TEAEs) by Severity [ Time Frame: Screening up to Follow-up (Week 11) ]
2. Observed Plasma Trough Concentration (Ctrough) of GLPG3970 [ Time Frame: Predose (within 30 minutes prior to dosing) on Days 15, 29 and 43 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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.

Contacts and Locations

Locations

Bulgaria

Medical Center Teodora

Ruse, Bulgaria, 7000

UMHAT Sv. Ivan Rilski EAD

Sofia, Bulgaria, 1431

Georgia

Aversi Clinic Ltd

Tbilisi, Georgia, 0160

Consilium Medulla-multiprofile clinic Ltd

Tbilisi, Georgia, 0186

Poland

Centrum Medyczne Grunwald

Poznan, Poland, 60-369

Centrum Badan Klinicznych S.C.

Poznań, Poland, 60-773

Ukraine

GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine

Kharkiv, Ukraine, 61039

SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU

Vinnytsia, Ukraine, 21029

Medical Center Clinic of Modern Rheumatology

Zaporizhzhya, Ukraine, 69005

Sponsors and Collaborators

Galapagos NV

Investigators

• Study Director: Antonio Speziale; Galapagos NV

More Information

• Responsible Party: Galapagos NV
• ClinicalTrials.gov Identifier: NCT04577781
• Other Study ID Numbers: GLPG3970-CL-209; 2020-000658-83 ( EudraCT Number )
• First Posted: October 8, 2020
• Last Update Posted: July 1, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Galapagos NV:

Arthritis; Rheumatic Diseases; Moderately active rheumatoid arthritis; Severely active rheumatoid arthritis; Joint Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Musculoskeletal and connective tissue disorders

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases