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)

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

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: GLPG3970; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Ruse, Bulgaria, 7000
    • Medical Center Teodora
  • Sofia, Bulgaria, 1431
    • Umhat Sv. Ivan Rilski Ead
• Georgia
  • Tbilisi, Georgia, 0160
    • Aversi Clinic LTD
  • Tbilisi, Georgia, 0186
    • Consilium Medulla-multiprofile clinic Ltd
• Poland
  • Poznan, Poland, 60-369
    • Centrum Medyczne Grunwald
  • Poznań, Poland, 60-773
    • Centrum Badan Klinicznych S.C.
• Ukraine
  • Kharkiv, Ukraine, 61039
    • GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
  • Vinnytsia, Ukraine, 21029
    • SRI of Invalid Rehabilitation (EST Complex) of Vinnytsia M.I.Pyrogov NMU MOHU
  • Zaporizhzhya, Ukraine, 69005
    • Medical Center Clinic of Modern Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GLPG3970; Participants received 400 milligrams (mg) GLPG3970 oral solution, once daily (QD) for a period of 6 weeks.	Drug: GLPG3970; GLPG3970 powder and solvent for oral solution to be reconstituted prior to use.
PLACEBO_COMPARATOR: Placebo; Participants received GLPG3970 matching placebo oral solution, QD for a period of 6 weeks.	Drug: Placebo; Placebo powder and solvent for oral solution to be reconstituted prior to use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in DAS-28 (CRP) at Week 6	The DAS28 (CRP) is a derived measurement with differential weighting given to each component such as TJC28, SJC28, patient's global assessment of disease activity, and serum CRP level.; TJC28 ranges from 0-28; SJC28 ranges from 0-28; High sensitivity C-reactive protein (hsCRP) (in mg/L); Patient's disease activity VAS (in mm) (ranges from 0 = best to 100 = worst) The DAS28 (CRP) score was calculated using the below formula: DAS28 (CRP) = 0.56 x square root of TJC28 + 0.28 x square root of SJC28 + 0.36 x Ln[1+CRP(in mg/L)] + 0.014 x patient's disease activity VAS (in mm) + 0.96. A lower score is considered as better disease activity.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration (Ctrough) of GLPG3970	Ctrough was defined as plasma concentration level at the end of the dosing interval.	Day 15: pre-dose; Day 29: pre-dose; Day 43: pre-dose
Number of Participants With Treatment Emergent Adverse Events	Treatment-Emergent Adverse Events (TEAE) were defined as; Any adverse event (AE) with an onset date on or after the IP start date and no later than 14 days after last dose of IP, or worsening of any AE on or after the IP start date.; Improvement or no change of any ongoing AEs on or after the IP start date are not considered treatment-emergent. If an AE was ongoing at the time of first IP intake and if there was no change or an improvement in its toxicity grade or its seriousness status, this AE was not considered as treatment-emergent. Serious TEAE was defined as a TEAE that; Resulted in death and was life-threatening;; Required in-patient hospitalization or prolongation of existing hospitalization;; Resulted in persistent or significant disability/incapacity;; Was a congenital anomaly / birth defect;; Was medically significant;	From first dose of study drug until end of the study (up to 8 weeks)

Collaborators and Investigators

• Sponsor: Galapagos NV

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 12, 2020
• Primary Completion (ACTUAL): March 26, 2021
• Study Completion (ACTUAL): April 7, 2021

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (ACTUAL): October 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 18, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Arthritis; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Musculoskeletal and connective tissue disorders; Moderately active rheumatoid arthritis; Severely active rheumatoid arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: GLPG3970-CL-209; 2020-000658-83 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No