E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that targets the synovial tissues [O’Dell, 2004]. The synovial inflammation may cause irreversible cartilage destruction and erosion of bone |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042952 |
E.1.2 | Term | Systemic rheumatoid arthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 |
The primary objective of this study is to evaluate the long-term safety and efficacy of ASP015K in subjects with Rheumatoid Arthritis (RA) who have completed a preceding ASP015K RA study |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is an optional substudy. Subjects who consent to participate in the optional mRNA sub-study will have blood samples collected during the Baseline visit, after Randomization, but prior to the first dose of study drug, and at weeks 25, 49, 73, and end of treatment/ early termination, and stored for exploratory mRNA expression profiling to better understand the pathological mechanisms involved in RA and the effects of ASP015K on whole blood gene expression. |
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E.3 | Principal inclusion criteria |
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the Subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
2. Male or female subject is at least 18 years of age at the time of Informed Consent.
3. Subject completed the week 12 visit in one of the Phase 2, ASP015K RA studies within the previous 14 days.
4. Female subject must be either:
Of non child bearing potential:
o Post-menopausal (defined as at least 1 year without any menses) prior to
enrollment, or
o Documented surgically sterile or status post hysterectomy (at least 1 month
prior to enrollment)
Or, if of childbearing potential,
o Must have a negative urine pregnancy test at enrollment, and
o Must use two forms of birth control1 (at least one of which must be a barrier
method) starting at enrollment and throughout the study period and for 60
days] after the final study drug administration.
5. Female subject must not be breastfeeding at Baseline/Day 1 or during the study period, and for 60 days after final study drug administration.
6. Female subject must not donate ova starting at Baseline/Day 1 and throughout the study period, and for 60 days after final study drug administration.
7. Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Baseline/Day 1 and continue throughout the study period and for 90 days after the final study drug administration.
8. Male subject must not donate sperm starting at Baseline/Day 1 and throughout the study period, and for at least 90 days after final study drug administration.
9. Subject must be willing and able to comply with the study requirements.
10. Subject agrees not to participate in another interventional study while on treatment. |
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E.4 | Principal exclusion criteria |
Subject will be excluded from participation if any of the following apply:
1. Subject has any condition considered by the Principal Investigator or Medical Monitor to preclude adequate evaluation of drug safety.
2. Subject is scheduled to receive any investigational drug other than ASP015K during the course of the study.
3. Subject is scheduled to receive a prohibited medication.
4. Subject has a planned major surgery.
5. Subject discontinued study drug due to meeting study drug discontinuation criteria prior to completion of the Week 12 visit in the preceding study or fulfills study drug discontinuation criteria at the final study visit of the preceding study.
6. Subject has any of the following laboratory values within the preceding 14 days prior to Day 1 study dosing, confirmed on re-test:
Hemoglobin < 8 g/dL
White blood cell count < 2000/mm3
Absolute neutrophil count (ANC) < 1000/mm3
Absolute lymphocyte count (ALC) < 500/mm3
Platelet count < 50,000/mm3
ALT ≥ 3 x upper limit of normal
AST ≥ 3 x upper limit of normal
Total bilirubin ≥ 2 x upper limit of normal
CPK > 1.5x upper limit of normal unless the level has been stable for at least 2
consecutive blood draws (at least 7 days apart), and subject does not have symptoms of muscle aching, weakness, or severe unusual muscle cramps. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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) |
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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 | 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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |