Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2017-001944-36-ES
• Date of registration: 10/10/2017
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis
• Scientific title: A Phase 1b/2a Study to Evaluate the Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis With Inadequate Response to Standard of Care Therapy
• Date of first enrolment: 21/05/2018
• Target sample size: 137
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001944-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Czech Republic, Germany, Mexico, New Zealand, Poland, Romania, Spain, United Kingdom, United States

Contacts

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info - Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Subject has provided informed consent prior to initiation of any study specific
activities/procedures.
- Age = 18 to = 70 years of age at screening
- A diagnosis of RA consistent with the 1987 or 2010 American College of
Rheumatology (ACR)/European League Against Rheumatism classification
criteria
- Active RA defined as:
• Phase 1b: DAS-28-CRP > 2.6 at screening. The 28-joint count consists of
the finger joints excluding the distal interphalangeal joints, the wrists, elbows,
shoulders, and knees.
• Phase 2a: = 6 swollen joints (based on 66-joint count) and = 6 tender joints
(based on 68-joint count) at screening and baseline. The distal interphalangeal joint should be evaluated but not included in the total count to determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the upper limit of normal (ULN) per the central laboratory at screening.
- Receiving treatment with methotrexate for = 12 weeks and on a stable dose
= 15 mg weekly for = 8 weeks prior to day 1. A lower methotrexate dose is
acceptable (but no lower than 10 mg weekly) if it is the highest tolerated dose
and gastrointestinal or hematologic toxicity at doses = 15 mg weekly is
documented by the investigator.
- Receiving treatment with folic or folinic acid per investigator judgment or
according to local standard of care.
- Phase 1b only: Subject may be receiving a stable dose of leflunomide,
sulfasalazine, hydroxychloroquine, minocycline in combination with methotrexate and the dose must be stable for = 8 weeks prior to day 1.
- Subject may be receiving a stable dose of prednisone = 10mg daily or other
equivalent corticosteroid dose and the dose must be stable for = 2 weeks prior to
day 1.
- Phase 1b only. Normal or clinically acceptable ECG values (12-lead reporting
ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline
based on opinion of the investigator.
- Immunizations (tetanus, diphtheria, pertussis, seasonal influenza [during flu
season], and pneumococcal [polysaccharide] vaccinations) up to date per local
standards as determined by the investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 47

Exclusion criteria:
Disease Related:
- Class IV RA according to ACR revised response criteria
- Diagnosis of Felty’s Syndrome (RA, splenomegaly and granulocytopenia)
Other Medical Conditions
- Prosthetic joint infection within 3 years of screening or native joint infection within 1 year prior to screening.
- Active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to day 1.
- Known history of active tuberculosis
- Positive test for tuberculosis during screening
- Positive for hepatitis B surface antigen, hepatitis B core antibody .
- Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or
known to be HIV positive. Phase 2a only: Known history of HIV
- Positive drug or alcohol urine test at screening.
- Presence of one or more significant concurrent medical conditions per
investigator judgment, including but not limited to the following:
• poorly controlled diabetes or hypertension
• chronic kidney disease stage IIIb, IV, or V
• symptomatic heart failure (New York Heart Association class II, III, or IV)
• myocardial infarction or unstable angina pectoris within the past
12 months prior to randomization
• severe chronic pulmonary disease (eg, requiring oxygen therapy)
• multiple sclerosis or any other demyelinating disease
• major chronic inflammatory disease or connective tissue disease other
than RA
- Malignancy except non-melanoma skin cancers, cervical or breast ductal
carcinoma in situ within the last 5 years.
- History of alcohol or substance abuse within 6 months of screening
- Phase 1b only: Current smoker, and/or use of any nicotine or tobacco containing products within the last 6 months prior to day 1.
- Phase 1b only: Subject unwilling to limit alcohol consumption
Subjects who have received intra-articular or systemic corticosteroid injections
for treatment of acute RA flare (not being part of a regular therapeutic regimen)
within 4 weeks prior to screening.
- Currently receiving or had treatment with cyclophosphamide, chlorambucil,
nitrogen mustard, or any other alkylating agent = 6 months prior to day 1.
- Prior use of > 1 biologic DMARD and prior use of a biologic DMARD occurred as
follows:
• = 10 weeks prior to day 1 for infliximab, abatacept, tocilizumab, golimumab, certolizumab pegol, adalimumab
• = 4 weeks prior to day 1 for etanercept and anakinra
• = 6 months for rituximab
Note: Bio-naïve subjects, defined as subjects who have never received prior biologic therapy for the treatment of RA, are excluded from entering the study in Spain.
- Currently receiving or had treatment with any of the following = 12 weeks prior to day 1:
• azathioprine
• cyclosporine
• gold
• mycophenolate mofetil
• Prosorba column
• Tacrolimus
- Phase 2a only: Currently receiving or had treatment with leflunomide = 12 weeks prior to day 1 unless an active washout with cholestyramine has been performed.
- Phase 2a only: Currently receiving or had treatment with any of the following
= 4 weeks prior to day 1:
• hydroxychloroquine
• sulfasalazine
• minocycline
• oral janus kinase inhibitor (eg, tofacitinib, baricitinib)
• intra-articular, intramuscular or intravenous corticosteroids, including
adrenocorticotropic hormone
• intra-articular hyaluronic acid injections
• live vaccines
- Unstable dose of non-steroidal anti-inflammatory drugs (NSAID), aceta

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Immune system processes [G12]

Rheumatoid Arthritis
MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870

Intervention(s)

Product Name: AMG592
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMG 592
Current Sponsor code: AMG 592
Other descriptive name: RECOMBINANT FACTOR FC FUSION PROTEIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Phase 1b
• To evaluate the safety and tolerability of subcutaneous (SC) dose administrations of AMG 592 in subjects with active RA
Phase 2a
• To evaluate the efficacy of AMG 592 at week 12 as measured by the American
College of Rheumatology 20% improvement criteria (ACR 20) in adult subjects with moderate to severe RA

Primary end point(s): Phase 1b
• Treatment-emergent adverse events.
• Clinically significant changes in vital signs, laboratory safety tests, and electrocardiograms (ECGs)

Phase 2a
• ACR 20 at week 12

Timepoint(s) of evaluation of this end point: Throughout study, Week 12

Secondary Objective: Phase 1b
• To characterize the pharmacokinetic (PK) profile following treatment with AMG 592
• To evaluate the incidence of anti-AMG 592 antibody formation and cross-reactivity to human IL-2.
Phase 2a
• To evaluate the effect of treatment with AMG 592 on other measures of disease
• To evaluate the safety of AMG 592
• To characterize the PK of AMG 592 in subjects with RA activity at week 12

Secondary Outcome(s)

Secondary end point(s): Phase 1b
• AMG 592 serum concentration and PK parameters including, but not
limited to, maximum observed concentration (Cmax), the time of maximum observed concentration (Tmax), and area under the concentration-time curve (AUCtau) after the first and last doses. Area under the concentration-time curve
over the dosing interval will be calculated & reported for each dosing regimen.
• Anti-AMG 592 antibodies and
cross-reactivity to IL-2.
• Anti-AMG 592 and anti-IL 2 neutralizing antibodies
Phase 2a
• ACR 50/70 at weeks 12
• Disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS28-ESR) score and change from baseline at week 12
• Disease activity score (28 joint) calculated using the C-reactive protein formula
(DAS-28-CRP) score and change from baseline at week 12
Treatment-emergent adverse events.
• Clinically significant changes in vital signs, laboratory safety tests
- AMG 592 serum concentration and PK parameters

Timepoint(s) of evaluation of this end point: Throughout study, Week 12

Secondary ID(s)

20170149

Source(s) of Monetary Support

Amgen Inc.

Ethics review

Status: Approved
Approval date: 15/05/2018
Contact:

Results

• Results available: Yes
• Date Posted: 27/05/2021
• Date Completed: 10/12/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001944-36/results