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 |
Rheumatoid Arthritis is a chronic inflammatory disease causing pain and swelling in the joints. The cause of the disease is unknown. In addition, the disease can involve other tissues of the body. |
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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 | 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 efficacy of PF-06650833 at 12 weeks, in subjects with moderate - severe active RA who have had an inadequate response to methotrexate.
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of PF-06650833 for 12 weeks in subjects with RA.
- To explore the dose – response relationship for efficacy in RA.
- To assess other signs of clinical efficacy over 12 weeks.
- To assess the effect of PF-06650833 on patient reported outcome measurements. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive. For subjects >70 years old, the site must discuss subject eligibility with the study team to ensure that these subjects are sufficiently healthy to participate.
2.Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/10.
3.The subject has active disease at both Screening and Baseline, as defined by both:
• ≥6 joints tender or painful on motion, AND
• ≥6 joints swollen;
and fulfills 1 of the following 2 criteria at Screening:
• High sensitivity C reactive protein (hsCRP) >7 mg/L at screening
• Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;
4. Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
5. Subjects must be seropositive at the time of randomization (ACPA positive).
6. Subjects must have been taking oral or equivalent parenteral (IM or SC , only; IV administration is not permitted) MTX for at least 3 months(prior to baseline randomization) at an adequate dose to determine that the subject had an inadequate response to MTX
7. Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered in accordance with its labeling recommendations. The TNF-inhibiting biologic could have been discontinued due to its being deemed inadequately effective and/or not tolerated. |
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E.4 | Principal exclusion criteria |
1. Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
2. Subjects with any of the following infections or infections history:
a. Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
b. Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
c. Infected joint prosthesis at any time with the prosthesis still in situ.
d. Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
e. Subjects will be screened for HIV (unless local regulations prohibit
mandatory testing). Subjects who test positive for HIV will be excluded from the study.
f. Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HbsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
g. Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
h. Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.
3. Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
4. Pre-existing chronic autoimmune disease.
5. Subjects with fibromyalgia will be excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the SDAI. |
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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) |
Clinical Efficacy Endpoints:
- Change from baseline in SDAI.
- SDAI low disease activity score (LDAS) and remission rates.
- DAS28 LDAS and remission rates.
- Change from baseline DAS28-3, DAS28-3 (CRP), DAS28 -4 (ESR), and DAS28-4 (CRP).
- ACR 20, ACR 50, and ACR 70 responder rates.
- Change from baseline in the Tender/Painful and Swollen Joint Counts.
- Change from baseline in hsCRP.
- Change from baseline in the Physician’s Global Assessment of Arthritis (PhGA).
Safety Endpoints:
- Safety and tolerability of PF-06650833: vital signs (blood pressure, pulse, and temperature), laboratory tests, Adverse Events (AEs) and Serious Adverse Events (SAEs), 12-lead ECG.
- Urinalysis including urine microscopy. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 60 |
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 |
Australia |
Bosnia and Herzegovina |
Bulgaria |
Colombia |
Croatia |
Czech Republic |
Georgia |
Germany |
Hungary |
Korea, Republic of |
Mexico |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
Spain |
Taiwan |
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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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 | 5 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |