E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of GLPG3970 compared to placebo on the signs and symptoms of Rheumatoid Arthritis (RA) in subjects with moderately to severely active RA and an inadequate response to methotrexate (MTX). |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of GLPG3970 compared to placebo in subjects with moderately to severely active RA and an inadequate response to MTX.
- To characterize the PK of GLPG3970 in subjects with moderately to severely active RA and an inadequate response to MTX |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subject ≥18 and <65 years of age, on the date of signing the informed consent form (ICF).
2. A body mass index (BMI) between 18–32 kg/m2, inclusive.
3. Diagnosis of RA ≥6 months prior to screening AND meeting the 2010 ACR/ EULAR criteria of RA AND ACR functional class I-III.
4. Have ≥6 swollen joints (from a SJC66) AND ≥8 tender joints (from a TJC68) at screening and at the baseline visit (Visit 1) prior to the first IP dosing.
5. DAS28 (CRP) >3.2 (moderate disease) at screening.
6. Screening serum high sensitivity CRP (hsCRP) > upper limit of normal (ULN, central laboratory reference: ≤ 5.0 mg/L).
7. Inadequate response to MTX, i.e. treatment-experienced subjects who demonstrated inadequate clinical response during treatment with MTX.
8. 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.
9. 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.
This list only contains the key inclusion criteria. |
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E.4 | Principal exclusion criteria |
1. Current therapy with any conventional disease-modifying anti-rheumatic drug (DMARD) other than MTX, including
a. oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D-penicillamine within 4 weeks prior to screening,
b. cyclosporine within 8 weeks prior to screening, and
c. 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 subjects who received bDMARDs only in a single clinical study setting:
a. For whom the last dose of bDMARD ≥6 months prior to screening (12 months for rituximab or other lymphocyte depleting agents), AND;
b. For whom the bDMARD was effective, without being discontinued due to lack of efficacy.
3. Subjects who received an intra-articular or parenteral corticosteroid injection within 4 weeks prior to screening.
4. Subjects who received a prior surgical intervention within 12 weeks prior to screening or likely requirement for surgery during the study.
5. Subject 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:
a. Positive QuantiFERON-TB Gold test result at screening, OR
b. 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. Subject 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. Subject 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. Subject has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV surface antigen (HBsAg) positivity. Subject has hepatitis C virus (HCV) infection, as defined by positive HCV antibody at screening and detectable HCV viremia. Subjects with positive HCV antibody must undergo reflex HCV RNA testing, and subjects with
HCV RNA positivity will be excluded. Subjects with positive HCV antibody and negative HCV RNA are eligible.
9. Subject testing positive at screening for SARS-CoV-2 infection as detected by real time polymerase chain reaction (RT-PCR), subjects 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 subjects 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.
This list only contains the key exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in DAS28 (C-reactive protein [CRP]) at Week 6. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At baseline and at week 6. |
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E.5.2 | Secondary end point(s) |
- Number, incidence and severity of treatment-emergent adverse events (TEAEs).
- Observed GLPG3970 plasma trough concentrations (Ctrough). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints during the trial as per clinical study design. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Georgia |
Poland |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 7 |