E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
active rheumatoid arthritis |
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E.1.1.1 | Medical condition in easily understood language |
arthritis due to overactive immune system |
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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 | 16.0 |
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 |
|
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 determine the optimal dose of MK-8457 + MTX as compared to
placebo + MTX, as demonstrated the RA subjects who achieve ACR20 response after 12 weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
To determine the effects of 12 weeks of treatment with MK-8457 100 mg BID + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, ACR-N, change from baseline in individual ACR components, DAS28CRP and DAS28ESR (including DAS28 response, DAS28 remission, and change from baseline, DAS-AUC), Simplified Disease Activity Index (SDAI), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), change from
baseline in Hemoglobin
(2)To determine the effects of 12 weeks of treatment with all other doses of MK-8457 + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, and change from baseline in individual ACR
components, DAS28, SDAI, ESR, CRP, SF-36, HAQ, and FACIT-F. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject must be ≥18 years of age on the day of signing the informed consent.
RA diagnosis and disease activity:
Subject has a diagnosis of RA (according to revised 1987 criteria of the ARA) for at least 6 months prior to screening.
Subject has active RA as defined by the presence of 6 swollen joints (of 66 joint count) AND 6 tender joints (of 68 joint count) at screening (Visit 1) and baseline (Visit 2).
Subject has a C-reactive protein (CRP) blood level > 0.9 mg/dL from the central reference laboratory at screening.
Subject is anti-cyclic citrullinated antibody positive and/or rheumatoid factor positive at screening.
Subject is ACR functional Class I, II, or III.
Subjects has received MTX for a minimum of 3 months prior to screening with a regionally appropriate stable weekly dose (7.5-25 mg/wk for regions outside of Asia, 6–25 mg/week for Asia) for at least 4 wks prior to screening. |
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E.4 | Principal exclusion criteria |
• Subject has inflammatory disease other than RA and secondary Sjogren's, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease that may confound the evaluation of the efficacy of MK-8457.
• Previous exposure to fostamatinib or other splenic tyrosine kinase (SYK) inhibitors.
• Previous exposure to TNF-alpha targeted therapy or any biological agents for RA.
• Subject has received any treatment listed below more recently than the indicated washout period prior to Screening.
Prohibited Medications, Supplements, and Other Substances Washout Period Prior to Screening
Disease modifying anti-rheumatic drugs such as but not limited to (not including cytotoxic agents):
Leflunomide, cyclosporine, mycophenolate mofetil, azathioprine, corticosteroids (parenteral, intra-articular), sulfasalazine, hydroxychloroquine 30 days (8 weeks for leflunomide unless subject undergoes standard cholestyramine or activated charcoal washout)
Cytotoxic agents including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents 3 months
Live vaccinations 1 month
Investigational medications 30 days or 5 half lives of the investigational agent whichever is longer
Bacille Calmette-Guerin (BCG) vaccination 1 month
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E.5 End points |
E.5.1 | Primary end point(s) |
American College of Rheumatology 20 (ACR20) response at 12 weeks |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Objective: To determine the effects of 12 weeks of treatment with MK-8457 100 mg BID + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, ACR-N, change from baseline in individual ACR components, DAS28CRP, DAS28ESR (DAS28 response, DAS28 remission, and change from baseline) DAS-AUC, Simplified Disease Activity Index (SDAI), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), change from baseline in Hemoglobin
(2) Objective: To determine the effects of 12 weeks of treatment with all other doses of MK-8457 + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, and change from baseline in individual ACR components, DAS28, SDAI, ESR, CRP, SF-36, HAQ, and FACIT-F.
|
|
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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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 | 6 |
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 |
Brazil |
Canada |
Chile |
Denmark |
Germany |
Hungary |
India |
Japan |
Korea, Democratic People's Republic of |
Lithuania |
Mexico |
Moldova, Republic of |
Peru |
Poland |
Russian Federation |
South Africa |
Taiwan |
United Kingdom |
United States |
|
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |