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

NCT03156023 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 201501962017-000337-31
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 4

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).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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.

Study Arms (2)

Rozibafusp Alfa

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses).

Drug: Placebo

Interventions

Rozibafusp Alfa DRUG

Administered by subcutaneous injection once every 2 weeks.

Also known as: AMG 570

Rozibafusp Alfa

Placebo DRUG

Administered by subcutaneous injection once every 2 weeks.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (4)

Pinnacle Research Group LLC

Anniston, Alabama, 36207, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

Location

Charite Research Organisation GmbH

Berlin, 10117, Germany

Location

Related Publications (1)

• 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.

  PMID: 37150935 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

rozibafusp alfa

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 16, 2017
• Study Start: August 14, 2017
• Primary Completion: October 17, 2019
• Study Completion: June 12, 2020
• Last Updated: May 14, 2024
• Results First Posted: April 3, 2023

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (3); DE (1)