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 | 16.1 |
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 efficacy of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy.
To evaluate the safety and tolerability of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of multiple doses of VX-509 when administered for 24 weeks
To evaluate the safety and tolerability of multiple doses of VX-509 when administered for 24 weeks
To investigate the PK of VX-509 after multiple doses of VX-509 are administered
To investigate the effect of VX-509 on the PK of MTX, after multiple doses of VX-509 are administered
To determine the pharmacodynamic relationships between the exposure of VX-509, MTX, and biomarker responses
To evaluate the durability of efficacy during the OLE
To determine whether subjects who receive their first dose or a higher dose of VX-509 during the OLE attain or increase their level of efficacy
To evaluate the safety and tolerability of chronic administration of VX-509 during the OLE |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects, between 18 and 80 years of age (inclusive)
2. All subjects must have been diagnosed with RA
3. Must have a swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
4. Baseline CRP level must be above the upper limit of normal
5. All subjects must have been receiving stable MTX coadministered with folic or folinic acid (at least 5 mg/week)
6. Subjects may remain on 1 nonsteroidal anti-inflammatory medication during the study (aspirin ≤ 325 mg/day is allowed).
7. Subjects must not have received prior treatment with a JAK inhibitor
8. Subjects who are on an additional nonbiologic DMARD (e.g., sulfasalazine) must be willing to discontinue that DMARD after signing consent, except for hydroxcychloroquine
9. Subjects may have received previous therapy with a single TNF inhibitor (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol)
10. Females must have a negative pregnancy test prior to study dosing
11. Sexually active subjects and their partners must agree to contraceptive requirements
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E.4 | Principal exclusion criteria |
1. History or presence of a clinically significant medical disorder other than RA that, in the opinion of the investigator and medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
2. Subjects with inflammatory, rheumatological disorders other than RA
3. Pregnant or nursing female subjects
4. Subjects who have a female partner who is pregnant, nursing, or planning to become pregnant
5. Subjects who have planned major surgery (e.g., joint replacement) or procedures during the study
6. History of drug abuse or positive drug screen
7. History of alcohol abuse or excessive alcohol consumption
8. History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who achieve a 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP) response [Time Frame: Week 12]
Change from baseline in Disease Activity Score 28 using C-reactive protein calculated using the formula with 4 variables (DAS28-4[CRP]) [Time Frame: Week 12]
Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs [Time Frame: 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 primary outcome measures at 24 weeks
Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses [Time Frame: Week 12 and 24]
Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria [Time Frame: Week 12 and 24]
Proportion of subjects who achieve remission as defined by DAS28-4 (CRP) response [Time Frame: Week 12 and 24]
Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission [Time Frame: Week 12 and 24]
Change from baseline in selected Patient Reported Outcomes (PROs) [Time Frame: Week 12 and 24]
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
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 | 5 |
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 | 51 |
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 |
Romania |
Slovakia |
Argentina |
Czech Republic |
Estonia |
Germany |
Hungary |
Mexico |
Peru |
Poland |
Russian Federation |
Serbia |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the study is defined as the date of final database lock. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |