Rheumatoid Arthritis MedDRA version: 17.0 Level: LLT Classification code 10042952 Term: Systemic rheumatoid arthritis System Organ Class: 100000004859
Conditions
Interventions
Product Code: IPI 145
Pharmaceutical Form: Capsule
CAS Number: 1201438-56-3
Other descriptive name: IPI-145
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Ph
Sponsors
Infinity Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for participation in the study: 1. Male or female adults =18 and =70 years of age 2. Meet the 1987 ACR criteria for RA 3. ACR functional class I-III 4. Have =5 swollen AND =5 tender joints (based on 66 and 68 joint counts, respectively) at Screening and Baseline 5. C-reactive protein >7 mg/L (>1.4 x ULN for central laboratory) at Screening 6. Positive laboratory result at Screening for RF and/or ACPA 7. RA disease duration of at least 6 months 8. Must be taking MTX for at least 3 months prior to Screening, and on a stable dose and route for at least 6 weeks prior to dosing (Day 1); stable doses must be - 7.5 to 25.0 mg once per week (split doses are permitted) - if dose is =65 years) yes F.1.3.1 Number of subjects for this age range 187
Exclusion criteria
Exclusion criteria: Subjects are to be excluded from the study if they meet any of the following criteria: 1. Any prior treatment with a PI3K inhibitor in a previous clinical study 2. History of allergy or reaction to any component of the study drug formulation, such as excipients in the study drug capsule (See Section 7.1) 3. Use of more than 1 nonsteroidal anti-inflammatory drug (NSAID) or use of a single agent at a dose higher than indicated for treatment of RA within 4 weeks of dosing (Day 1) (note: any chronic NSAID dose must remain stable from 4 weeks prior to dosing [Day 1]) 4. Previous failure or inadequate response to >2 biologic DMARDs 5. Use of the following medications to treat RA: - oral or injectable gold, etanercept, anakinra, or tofacitinib within 30 days prior to dosing (Day 1) - cyclosporine, azathioprine, abatacept, infliximab, tocilizumab or adalimumab within 60 days prior to dosing (Day 1) - leflunomide within 180 days prior to dosing (Day 1), unless receipt of appropriate course of cholestyramine for washout (cholestyramine 8 g TID for 11 days) at least 30 days prior to dosing (Day 1) - cyclophosphamide within 180 days prior to dosing (Day 1) - rituximab within 180 days prior to dosing (Day 1); subjects with a history of rituximab use must have a normal CD19 count at Screening - parenteral or intra-articular corticosteroids, or other immunosuppressive therapy within 30 days prior to dosing (Day 1) - other immunosuppressive agents or non-biologic DMARD within 30 days or 5 half-lives (whichever is longer) prior to dosing (Day 1) 6. Concurrent administration of medications or foods known to be strong or moderate inhibitors or inducers of CYP3A (see Appendix 3). 7. Acute or ongoing clinically significant infection (includes clinically significant upper respiratory tract infections) as determined by the Investigator within 4 weeks prior to Screening 8. Receipt of any live or attenuated vaccine within 30 days prior to dosing (Day 1) 9. Participation in another investigational drug study within 30 days prior to Screening, and willingness to refrain from participation in another investigational drug study until completion of the final Follow-up Visit 10. Clinically significant abnormalities on safety laboratory tests, 12-lead ECG, vital signs, physical examination or medical history at Screening or Baseline, based on the medical judgment of the Investigator; specific Screening safety laboratory values for exclusion include - Serum creatinine =2.0 mg/dL (177 µmol/L) - ALT, AST, or total bilirubin >1.5 x ULN [unless total bilirubin exclusion cut-off doesn't apply if subject has Gilbert’s Syndrome] - Hemoglobin <9 g/dL, WBC <3.0 x 109/L, absolute neutrophil count <1.2 x 109/L, or platelets <100×109/L 11. Evidence of active or prior hepatitis B or active hepatitis C infection at Screening 12. History of HIV infection, or known risk factors for HIV within 1 year of Screening (e.g., unprotected sexual intercourse with an HIV-infected individual) 1, 2 13. Positive or confirmed indeterminate screen result for active or latent tuberculosis (QuantiFERON-TB blood test at Screening) 14. History of or current pancreatitis (unless documented as due to gallstones, cholecystectomy has been performed, and no recurrence within 60 days prior to screening) 15. History of significant non-RA systemic disease (e.g., coronary artery disease, uncontrolled seizure disorder, cancer [except for adequately treated non-metastatic basal cell or sq
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Proportion of subjects who achieve a 20% improvement in the American College of Rheumatology Criteria (ACR20) from Baseline to Week 12;Timepoint(s) of evaluation of this end point: From baseline to week 12.;Main Objective: Evaluate the efficacy of multiple dose levels of IPI 145 compared to placebo in subjects with moderate-to-severe active rheumatoid arthritis (RA) taking a stable dose of methotrexate (MTX);Secondary Objective: The secondary objectives are: Evaluate the safety of multiple dose levels of IPI 145 compared to placebo in subjects with moderate-to-severe active RA taking a stable dose of MTX Characterize the pharmacokinetics (PK) of IPI-145 in subjects with moderate-to-severe RA taking a stable dose of MTX | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Proportion of subjects who achieve an ACR20 over Week 4 through Week 12, based on a repeated measures model • Proportion of subjects who achieve an ACR20 from Baseline to Weeks 2, 4, 6, 8, and 10 • Proportion of subjects who achieve a 50% improvement in ACR Criteria (ACR50) from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 • Proportion of subjects who achieve a 70% improvement in ACR Criteria (ACR70) from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 • Change in the number of tender/painful joints from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 (68 joint count) • Change in the number of swollen joints from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 (66 joint count) • Change in the health assessment questionnaire disability index (HAQ-DI) from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 • Change in subject assessment of pain from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 (VAS 100 mm) • Change in subject global assessment of disease activity from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 (VAS 100 mm) • Change in physician global assessment of disease activity from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 (VAS 100 mm) • Change in C-reactive protein (CRP) from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 • Change in the 3-variable Disease Activity Score in 28 joints (DAS28)-CRP from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 • Proportion of subjects who achieve a response on the DAS28-CRP from Baseline to each of Weeks 2, 4, 6, 8, 10, and 12 Safety Endpoints: • Adverse events (AEs) • Safety laboratory findings PK Endpoints: • Pharmacokinetic parameters derived from plasma IPI-145 concentrations ;Timepoint(s) of evaluation of this end point: From baseline through to week 12 (every two weeks) | — |
Countries
Bulgaria, Colombia, Germany, Hungary, Mexico, New Zealand, Poland, Romania, Russian Federation, Serbia, Ukraine
Contacts
Public ContactLaura DiMarzio
Infinity Pharmaceuticals, Inc
Outcome results
None listed