Multiple Ascending Doses of Rozibafusp Alfa (AMG 570) in Adults With Rheumatoid Arthritis
- Registration Number
- NCT03156023
- Lead Sponsor
- Amgen
- Brief Summary
A study to evaluate safety and tolerability and characterize the pharmacokinetic (PK) profile of rozibafusp alfa following multiple dose administration in adults with rheumatoid arthritis (RA).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- Body Mass Index: 18-35 kg/m^2
- Diagnosed with RA (disease duration of at least 6 months)
- Stable dose of methotrexate (5-25 mg weekly for ≥ 4 weeks)
- Immunizations up to date
- Willing to use highly effective contraception during treatment and through end-of-study
- Uncontrolled, clinically significant systemic disease other than RA (i.e., diabetes mellitus, liver disease, asthma, cardiovascular disease, hypertension)
- Malignancy within 5 years
- Presence of serious infection, recurrent/chronic infections
- Class IV RA according to American College of Rheumatology/ (ACR) revised response criteria
- Diagnosed with Felty's syndrome
- Known or suspected sensitivity to mammalian cell-derived products
- History of alcohol and/or substance abuse within the last 12 months
- Receipt of rituximab at any time in the past
- Evidence of renal disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses). Rozibafusp Alfa Rozibafusp Alfa Participants will receive rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses). Rozibafusp alfa doses will range from 70 to 420 mg. Escalation to a higher dose cohort will be contingent on a review indicating that the previous dose regimen has been found to demonstrate an acceptable safety and tolerability profile at a dose level review meeting (DLRM).
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events From first dose of study drug to 24 weeks after last dose (up to 34 weeks). An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition and clinically significant changes in laboratory test results and physical exam findings. The event does not necessarily have a causal relationship with study treatment.
AEs were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe or medically significant, Grade 4 = Life-threatening, and Grade 5 = Death.
A serious adverse event is defined as an AE that met at least 1 of the following serious criteria:
* fatal;
* life threatening;
* required in patient hospitalization or prolongation of existing hospitalization;
* resulted in persistent or significant disability/incapacity;
* congenital anomaly/birth defect;
* other medically important serious event. The investigator assessed whether each AE was related to study drug.
- Secondary Outcome Measures
Name Time Method Accumulation Ratio of Cmax Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose Accumulation ratio is the ratio of Cmax after the last dosing interval (week 10) divided by Cmax after the first dosing interval (day 1).
Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. Terminal Half-life of Rozibafusp Alfa Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose. Accumulation Ratio of AUCtau Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose Accumulation ratio is the ratio of AUCtau after the last dosing interval (week 10) divided by AUCtau after the first dosing interval (day 1).
Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa Day 1 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours post-dose. Week 10 predose and 6, 12, 24, 48, 72, 144, 168, and 336 hours and at 3, 4, 5, 6, 8, 10, and 12 weeks post-dose.
Trial Locations
- Locations (4)
Pinnacle Research Group LLC
🇺🇸Anniston, Alabama, United States
Metroplex Clinical Research Center
🇺🇸Dallas, Texas, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Charite Research Organisation GmbH
🇩🇪Berlin, Germany