Safety and Efficacy of AMG 592 in Subjects with Active Rheumatoid Arthritis
- Conditions
- Rheumatoid ArthritisMedDRA version: 20.0Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditionsSystem Organ Class: 100000004870Therapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2017-001944-36-ES
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
- 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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method