Rheumatoid Arthritis
Conditions
Keywords
Immune-mediated disease, Autoimmune disease, Dihydroorotate dehydrogenase (DHODH) inhibitors, PTC844, Rheumatoid arthritis
Brief summary
This study is designed to assess the safety, pharmacokinetics (PK), and biomarker effects of PTC844 compared to placebo in participants with active rheumatoid arthritis (RA).
Interventions
DRUGPTC844
PTC844 will be administered per schedule specified in the arm description.
DRUGPlacebo
Placebo matching to PTC844 will be administered per schedule specified in the arm description.
Sponsors
PTC Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Historical diagnosis of RA as per the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) diagnostic criteria. * Active RA disease with a threshold of moderate activity or higher as confirmed via DAS28-CRP (score of ≥3.2) at screening. * Naïve to disease-modifying treatments for RA or have had an inadequate response to background treatment for RA and/or inability to tolerate disease-modifying antirheumatic drugs, as per investigator's discretion. * Disease-modifying antirheumatic drugs should be stable and unchanged from 30 days prior to the start of the Screening Period and intend to remain stable and unchanged throughout the course of the study. * CRP of ≥5 milligrams (mg)/liter (L) at screening. Key
Exclusion criteria
* Presence of any clinically significant abnormality at screening, or prior or ongoing medical condition (for example, concomitant illness, psychiatric condition), surgical procedure, medical history, or physical findings that, in the investigator's opinion, could adversely affect the safety of the participant or could impair the assessment of study results. * Participants with Class IV RA. * Past medical history of blood dyscrasia, bone marrow abnormality and/or suppression, drug induced thrombocytopenia or idiopathic thrombocytopenia, or bleeding diathesis. * Past medical history of inflammatory joint disease other than RA or fibromyalgia. * Rheumatoid arthritis onset at \<17 years of age. * Past medical history of malignancy within 5 years prior to screening, except for nonmelanoma skin cancers cursed via local resection. * Participant has a known hypersensitivity to any of the ingredients of PTC844 or to any excipients of the study drug. * Use or intended use of any prescribed disease-modifying treatments for RA within 30 days or 5 half-lives (whichever is longer) before the Screening Period until completion of the Follow-Up Visit, except for methotrexate, low dose prednisone (\<10 mg/day), hydroxychloroquine, or sulfasalazine, which are permitted as established background single-therapy medications. * Use or intended use of a combination of methotrexate, low dose prednisone (\<10 mg/day), hydroxychloroquine, or sulfasalazine within 30 days or 5 half-lives (whichever is longer) before the Screening Period until completion of the Follow-Up Visit. Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Baseline up to Week 16 |
| Change From Baseline to Week 2 in Dihydroorotate (DHO) | Baseline, Week 2 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline to Week 12 in C-reactive Protein (CRP) | Baseline, Week 12 |
| Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR) | Baseline, Week 12 |
| Change From Baseline in DHO Over Time | Baseline up to Week 16 |
| Maximum Observed Plasma Concentration (Cmax) of PTC844 | Baseline up to Week 16 |
| Area Under the Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) | Baseline up to Week 16 |
| Time to Reach Cmax (Tmax) | Baseline up to Week 16 |
| Number of Participants Achieving ≥20% Improvement in American College of Rheumatology Score (ACR20) | Week 12 |
| Number of Participants Achieving ≥50% Improvement in American College of Rheumatology Score (ACR50) | Week 12 |
| Number of Participants Achieving ≥70% Improvement in American College of Rheumatology Score (ACR70) | Week 12 |
| Change From Baseline to Week 12 in 28-Joint Disease Activity Score-CRP (DAS28-CRP) | Baseline, Week 12 |
| Change From Baseline to Week 12 in 28-Joint Disease Activity Score-ESR (DAS28-ESR) | Baseline, Week 12 |
| Change From Baseline to Week 12 in 20- Item Disability Scale and Heath Assessment Questionnaire (HAQ-DI) | Baseline, Week 12 |
Contacts
CONTACTPatient Advocacy
Outcome results
None listed