Multiple Ascending Doses of Rozibafusp Alfa (AMG 570) in Adults With Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Rozibafusp Alfa
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
- Body Mass Index: 18-35 kg/m2
- Diagnosed with RA (disease duration of at least 6 months)
- Stable dose of methotrexate (5-25 mg weekly)
- 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
- 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
Sites / Locations
- Pinnacle Research Group LLC
- Altoona Center for Clinical Research
- Metroplex Clinical Research Center
- Charite Research Organisation GmbH
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rozibafusp Alfa
Placebo
Arm Description
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).
Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa
Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa
Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa
Terminal Half-life of Rozibafusp Alfa
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03156023
Brief Title
Multiple Ascending Doses of Rozibafusp Alfa (AMG 570) in Adults With Rheumatoid Arthritis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
August 14, 2017 (Actual)
Primary Completion Date
October 17, 2019 (Actual)
Study Completion Date
June 12, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rozibafusp Alfa
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive matching placebo to rozibafusp alfa administered subcutaneously once every 2 weeks for up to 10 weeks (6 doses).
Intervention Type
Drug
Intervention Name(s)
Rozibafusp Alfa
Other Intervention Name(s)
AMG 570
Intervention Description
Administered by subcutaneous injection once every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered by subcutaneous injection once every 2 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events
Description
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.
Time Frame
From first dose of study drug to 24 weeks after last dose (up to 34 weeks).
Secondary Outcome Measure Information:
Title
Time to Maximum Observed Concentration (Tmax) of Rozibafusp Alfa
Time Frame
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.
Title
Maximum Observed Serum Concentration (Cmax) of Rozibafusp Alfa
Time Frame
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.
Title
Area Under the Concentration-time Curve From 0 to 14 Days Postdose (AUC0-tau) for Rozibafusp Alfa
Time Frame
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.
Title
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) for Rozibafusp Alfa
Time Frame
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.
Title
Terminal Half-life of Rozibafusp Alfa
Time Frame
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.
Title
Accumulation Ratio of AUCtau
Description
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 Frame
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
Title
Accumulation Ratio of Cmax
Description
Accumulation ratio is the ratio of Cmax after the last dosing interval (week 10) divided by Cmax after the first dosing interval (day 1).
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group LLC
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Metroplex Clinical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Charite Research Organisation GmbH
City
Berlin
ZIP/Postal Code
10117
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Multiple Ascending Doses of Rozibafusp Alfa (AMG 570) in Adults With Rheumatoid Arthritis
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