Multiple Ascending Doses of Rozibafusp Alfa (AMG 570) in Adults With Rheumatoid Arthritis

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Double Blind Placebo Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of AMG 570 in Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Rozibafusp Alfa
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rozibafusp Alfa<br>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). | Drug: Rozibafusp Alfa<br>* Administered by subcutaneous injection once every 2 weeks.<br>* Other names: AMG 570;|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses). | Drug: Placebo<br>* Administered by subcutaneous injection once every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events | 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. | From first dose of study drug to 24 weeks after last dose (up to 34 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| Accumulation Ratio of AUCtau | Accumulation ratio is the ratio of AUCtau after the last dosing interval (week 10) divided by AUCtau after the first dosing interval (day 1). | 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 of Cmax | Accumulation ratio is the ratio of Cmax after the last dosing interval (week 10) divided by Cmax after the first dosing interval (day 1). | 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 |