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] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 GS-9876 versus placebo for the treatment of signs and symptoms of RA in subjects with active RA as measured by change from baseline in DAS28 (CRP) at Week 12 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of GS-9876 in subjects with RA
- To explore the effect of GS-9876 on other disease-specific outcomes in RA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Active RA disease as defined by: a TJC of ≥ 6 (out of 68), an SJC of ≥ 6 (out of 66) at Screening and Day 1
2) Inadequate response to treatment with oral or parenteral MTX 7.5 to 25 mg/week continuously for at least 12 weeks, with at least 6 weeks at a stable dose (defined as no change in prescription) prior to the first dose of study drug
3) Subjects must be receiving a folic or folinic acid supplementation at a stable dose. Subjects who are not taking folic or folinic acid at Screening should be initiated on an adequate dose of folic acid (>5 mg/week total dose or as per local practice) or equivalent and maintained throughout the study.
4) Use of oral corticosteroids of no more than 10 mg prednisone or its equivalent per day is allowed if the dose is stable (defined as no change in prescription) for at least 28 days prior to the first dose of study drug
5) NSAIDs or other analgesics (including aspirin ≤ 100 mg daily) are allowed if doses are stable (defined as no change in prescription) for at least 14 days prior to the first dose of study drug; PRN use for other indications is allowed.
6) No evidence of active or latent TB as demonstrated by a negative QuantiFERON® TB-Gold In-Tube test at Screening. Tests with inconclusive results may be repeated one time. If an inconclusive test is repeated and is returned with inconclusive results a second time, the subject will be excluded from the study. Any prior history of active or latent TB (regardless of treatment) is exclusionary. |
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E.4 | Principal exclusion criteria |
1) Prior treatment with B-cell depleting agents (eg, rituximab), unless more than 6 months prior to the first dose of study drug and documented return of CD19+ cells at Screening
2) Prior treatment with any commercially available or investigational SYK inhibitor
3) Concurrent treatment at Screening with any other conventional synthetic DMARD (csDMARD) other than MTX and/or hydroxychloroquine (HCQ) (prior csDMARD treatment allowed if appropriate wash out as defined in Section 5.7)
4) Concurrent treatment at Screening with any bDMARD (prior bDMARD treatment allowed if appropriate wash out as
defined in Section 5.7). Prior failure to treatment with bDMARDs is not an exclusion criterion.
5) QT interval corrected for heart rate using the Fridericia formula (QTcF) > 450 msec determined by the average of values at the Screening visit
6) History of any major bleeding event defined as Grade 3 severity and above (as defined by modified the Common
Terminology Criteria for Adverse Events [CTCAE] 4.03 [Appendix 4]) within the last year or personal or family history of bleeding disorder
OR
Current use of chronic anticoagulant, not including daily aspirin for cardiac prophylaxis
7) Treatment with moderate or strong CYP3A inducers or inhibitors within 2 weeks prior to the first dose of study drug (examples are provided in Section 5.7) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in DAS28 (CRP) at Week 12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- The proportion of subjects who achieve ACR 20/50/70 at Week 12
- Change from baseline in HAQ-DI score at Week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | No |
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 | No |
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 | 4 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Czech Republic |
Hungary |
Poland |
Serbia |
Ukraine |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |