Combination Therapy of F8IL10 and Methotrexate in Rheumatoid Arthritis Patients
- Registration Number
- NCT02076659
- Lead Sponsor
- Philogen S.p.A.
- Brief Summary
Phase I, multicenter, open-label, dose escalation study to test the efficacy and safety of F8IL10 and methotrexate when given as a combination in rheumatoid arthritis patients.
- Detailed Description
The study is designed to explore whether F8IL10 can be safely administered in combination with standard-dose of MTX in patients with active rheumatoid arthritis and to determine the recommended dose of F8IL10 when combined with MTX.
As soon as the MTD/RD is determined, an additional 12 patients will be randomized (6+6) between F8IL10 (RD) and placebo to further investigate the safety and pharmacacodynamics profile of the study treatment.
Methotrexate (MTX) will be administered as concomitant medication in the dose escalation as well as in the randomized part of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description F8IL10 + MTX F8IL10 Ten cohorts of 3-6 RA patients will be treated at increasing doses per cohort of F8IL10 plus fixed doses of MTX and folic acid. An additional 12 patients will be randomized (6+6) in a double blind, placebo controlled cohort with F8IL10 given at RD and placebo. In both arms, MTX will be administered as concomitant medication. In all coohorts a stable dose of folic acid (5 mg) will be administered on Day 2. F8IL10 + MTX Methotrexate Ten cohorts of 3-6 RA patients will be treated at increasing doses per cohort of F8IL10 plus fixed doses of MTX and folic acid. An additional 12 patients will be randomized (6+6) in a double blind, placebo controlled cohort with F8IL10 given at RD and placebo. In both arms, MTX will be administered as concomitant medication. In all coohorts a stable dose of folic acid (5 mg) will be administered on Day 2.
- Primary Outcome Measures
Name Time Method Number of patients with adverse events that are related to treatment and classified as DLTs for each administered dosage Up to day 28 To establish the MTD and the RD of F8IL10 when administered in combination with methotrexate
- Secondary Outcome Measures
Name Time Method Accumulation ratio for Cmin [R min] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Response rate according to EULAR criteria (Good, Moderate and Non-responders) based on DAS28 score 1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up) To explore the antiarthritic activity of the study medication in patients with active rheumatoid arthritis.
Terminal half-life [t1/2] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Area under the drug concentration-time curve [AUC(0 - t last)] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Maximum drug concentration [Cmax] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
ACR 20, ACR 50, ACR 70 response rate 1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up) To explore the antiarthritic activity of the study medication in patients with active rheumatoid arthritis.
Area under the drug concentration-time curve, extrapolated to infinity [AUC] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Accumulation ratio for Cmax [Rmax] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Time to reach maximum drug concentration [Tmax] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Accumulation ratio for AUC [R AUC] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Relative change over time of blood biomarkers From day -14 up to day 0 (screening); at day 1 of week 1; at day 1 of week 5 /week 9 (EoT); from week 7 up to week 11 (safety follow-up); from week 11 up to week 15 (efficacy follow-up); from week 11-15 up to week 57-61, every 4 weeks (total follow-up) Total clearance following the dose administered [CL] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Volume of distribution at steady state [Vss] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Mean residence time [MRT] At day 1, 4, 5, 6 of week 1; at day 1, 2, 3, 4, 5, 6 of week 4 Pharmacokinetics assessment of F8IL10 through blood sampling
Human anti-fusion protein antibodies (HAFA) levels 1) at day 1 of week 1; 2) at day 1 of week 4; 3) from week 5 up to week 9 (EoT visit) Investigate the potential induction of human anti-fusion protein antibodies (HAFA) through standard laboratory analysis.
Change from baseline in DAS28 1) from day -14 up to day 0 (screening); 2) at day 1 of week 5; 3) at day 1 of week 9; 4) from week 9-13 up to week 57-61, every 4 weeks (safety/efficacy follow-up) To explore the antiarthritic activity of the study medication in patients with active rheumatoid arthritis.
Trial Locations
- Locations (5)
Azienda Ospedaliera San Camillo-Forlanini Roma
🇮🇹Roma, Italy
Policlinico San Matteo, Pavia
🇮🇹Pavia, Italy
Pisa University Hospital
🇮🇹Pisa, Italy
Siena University Hospital
🇮🇹Siena, Italy
Policlinico A. Gemelli, Università Cattolica del Sacro Cuore
🇮🇹Roma, Italy