Rheumatoid Arthritis MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870
Conditions
Interventions
Product Name: AMG 592
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMG592
Current Sponsor code: AMG592
Other descriptive name: AMG592
Concentration unit: mg/ml milligram(s)/millili
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion 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 102 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 51
Exclusion criteria
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 treatment with more than a total of 3 therapies that include biologic DMARDs or oral synthetic DMARDs (such as tofacinitib, baricitinib). Prior treatment consists of at least 4 doses of a given therapy where the doses were given solely for treatment of RA disease. Prior therapies must not have been used within the following time periods: • = 4 weeks prior to day 1 for etanercept and anakinra • = 6 months for rituximab • = 2 weeks for oral janus kinase inhibitiors • = 9 weeks prior to day 1 for all therapies not listed above - 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 inject
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;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;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
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Australia, Bulgaria, Czech Republic, Germany, Mexico, New Zealand, Poland, Romania, Spain, United Kingdom, United States
Contacts
Public ContactMedical Information
Amgen Biotechnologia Sp. z o.o.
Outcome results
None listed