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

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

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Rozibafusp Alfa; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite Research Organisation GmbH
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group LLC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Abuqayyas L, Chen PW, Dos Santos MT, Parnes JR, Doshi S, Dutta S, Houk BE. Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Properties of Rozibafusp Alfa, a Bispecific Inhibitor of BAFF and ICOSL: Analyses of Phase I Clinical Trials. Clin Pharmacol Ther. 2023 Aug;114(2):371-380. doi: 10.1002/cpt.2929. Epub 2023 May 24.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2017
• Primary Completion (Actual): October 17, 2019
• Study Completion (Actual): June 12, 2020

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 20150196; 2017-000337-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No