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] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of GLPG1690 as evaluated by mRSS compared to placebo over 24 weeks for the treatment of subjects with systemic sclerosis |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of GLPG1690 compared to placebo over 24 weeks in the treatment of subjects with systemic sclerosis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) as approved by the IEC/IRB, prior to any screening evaluations.
- Male and female subjects ≥18 years at the time of consent who meet the American College of Rheumatology (ACR)/EULAR 2013 diagnostic criteria (Van den Hoogen F. et al., 2013) for systemic sclerosis with diffuse cutaneous involvement (according to LeRoy’s criteria) and ≤5 years since the onset of the first systemic sclerosis manifestation other than Raynaud's phenomenon.
- mRSS >10 at screening.
- Active disease at screening, as defined by: Worsening of skin thickening (≥2 mRSS points) as assessed by mRSS measured at screening versus a previous mRSS assessment made within 6 months prior to screening, or new areas of skin involvement within 6 months prior to screening as documented by physician note, or new-onset systemic sclerosis with symptoms or signs other than Raynaud’s phenomenon within 2 years prior to screening, or ≥1 tendon friction rub (palpated in the finger flexors or extensors, wrist flexors or extensors, olecranon bursa, shoulders, knees, anterior or posterior ankles with active motion).
- Subject must be able and willing to comply with restrictions on prior and concomitant medication as described in the protocol
- Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
- Female subjects of childbearing potential or male subjects with female partners of childbearing potential must be willing to comply with the contraceptive methods described in the protocol prior to the first dose of the IMP, during the clinical study, and for at least 90 days after the last dose of the IMP for male subjects and 30 days after the last dose of the IMP for female subjects.
- A body mass index (BMI) between 18–35 kg/m2, inclusive, at screening.
- Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and fasting clinical laboratory safety tests. Clinical laboratory safety test results must be within the reference ranges or test results that are outside the reference ranges need to be considered non-clinically significant in the opinion of the investigator.
This list only contains the key inclusion criteria. |
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E.4 | Principal exclusion criteria |
- Known hypersensitivity to IMP ingredients or history of a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.
- Breastfeeding female or subject intending to become pregnant or breastfeed.
- History of or a current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection, congenital, acquired).
- Positive serology for hepatitis B (surface antigen) or C (antibody), or any history of hepatitis from any cause. For hepatitis A, a history of infection within 12 weeks prior to screening. Positive serology for HIV-1 and HIV-2 (antibodies).
- History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer medically managed through active surveillance or watchful waiting, and squamous cell carcinoma of the skin if fully resected).
- Clinically significant abnormalities detected on ECG at screening of either rhythm or conduction, QTcF >450 ms, or a known long QT syndrome.
- Unstable cardiovascular, pulmonary, or other disease (other than systemic sclerosis-related) within 6 months prior to the baseline visit (e.g. coronary heart disease, heart failure, stroke).
- Severe pulmonary disease with FVC ≤45% of predicted within 6 months prior to the baseline visit.
- Chronic or ongoing active infectious disease, including tuberculosis (requiring hospitalization or systemic treatment within 4 weeks prior to the baseline visit).
- Abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or bilirubin, and/or alkaline phosphatase >2x upper limit of normal (ULN). Retesting is allowed once.
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 mRSS over 24 weeks |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various timepoints during the trial as specified in the protocol |
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E.5.2 | Secondary end point(s) |
Incidence of TEAEs, serious adverse events (SAEs), AEs, and tolerability of GLPG1690 over 24 weeks |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints during the trial as specified in the protocol |
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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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Belgium |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |