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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03410056
Recruitment Status : Active, not recruiting
First Posted : January 25, 2018
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 3, 2018
First Posted Date  ICMJE January 25, 2018
Last Update Posted Date January 22, 2020
Actual Study Start Date  ICMJE May 22, 2018
Estimated Primary Completion Date September 9, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
ACR 20 [ Time Frame: Week 12 ]
The primary endpoint, ACR 20 at week 12, will be assessed between AMG 592 and placebo in the 2 populations respectively.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
  • ACR 50/70 [ Time Frame: Week 12 ]
    Evaluate the effect of treatment with AMG592 on ACR 50/70 change from baseline at week 12.
  • DAS28-ESR [ Time Frame: Week 12 ]
    Evaluate the effect of treatment with AMG on disease activity score (28 joint) calculated using the erythrocyte sedimentation rate formula (DAS28-ESR) score and change from baseline at week 12.
  • DAS 28-CRP [ Time Frame: Week 12 ]
    Evaluate the effect of treatment with AMG on disease activity score (28 joint) calculated using the c-reactive protein formula (DAS 28-CRP) score and change from baseline at week 12.
  • Maximum observed concentration (Cmax) of AMG592 [ Time Frame: Week 12 ]
    Analyze serum concentrations of AMG592
  • Time of maximum observed concentration (Tmax) of AMG592 [ Time Frame: Week 12 ]
    Analyze serum concentrations of AMG592
  • Area under the concentration-time curve (AUCtau) of AMG592 [ Time Frame: Week 12 ]
    Analyze serum concentrations of AMG592
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of AMG 592 in Subjects With Active Rheumatoid Arthritis
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis RA
Intervention  ICMJE
  • Drug: AMG 592
    AMG 592
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: AMG 592
    The phase 1b part of the study is a double-blind, placebo controlled, MAD study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMG 592 in subjects with active RA. The phase 2a part of the study will commence after a RP2D is identified in the phase 1b part of the study.
    Intervention: Drug: AMG 592
  • Placebo Comparator: Placebo
    The phase 1b part of the study is a double-blind, placebo controlled, MAD study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMG 592 in subjects with active RA. The phase 2a part of the study will commence after a RP2D is identified in the phase 1b part of the study.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 5, 2019)
153
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2018)
105
Estimated Study Completion Date  ICMJE September 9, 2022
Estimated Primary Completion Date September 9, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 today 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.

Exclusion Criteria:

  • Class IV RA according to ACR revised response criteria
  • Diagnosis of Felty's Syndrome (RA, splenomegaly and granulocytopenia).
  • 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 defined as either: positive purified protein derivative (PPD) (≥ 5 mm of induration at 48 to 72 hours after test is placed) OR positive Quantiferon test: a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest x ray; a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening: no symptoms per tuberculosis or sheet provided by Amgen; document history of a completed course of adequate prophylaxis(completed treatment for latent tuberculosis per local standard of care prior to the start of investigational product); no known exposure to a case of active tuberculosis after most recent prophylaxis; negative chest X-ray.
  • Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B DNA polymerase chain reaction [PCR] test) or detectable hepatitis C virus RNA by PCR (screening is generally done by hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B vaccination without history of hepatitis B is allowed.
  • Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or known to be HIV positive. Phase 2a only: Known history of HIV
  • Phase 1b only: Positive drug or alcohol urine test for illicit drugs at screening. Prescription medications detected by the drug test are allowed if they are being taken under the direction of a physician.
  • 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 (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome).
  • 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. These types of products include but are not limited to: snuff, chewing tobacco, cigars, electronic cigarettes, cigarettes, pipes, or nicotine patches.
  • Phase 1b only: Subject unwilling to limit alcohol consumption to ≤ 1 drink of alcohol per day and ≤ 3 drinks per week for the duration of the study, where a drink is equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits. Phase 1b only: Unwilling or unable to abstain from alcohol consumption within 48 hours prior to each visit (including screening).
  • 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 inhibitors
    • ≤ 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 injections
    • live vaccines
  • Unstable dose of non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, and/or analgesics which is taken on an unscheduled basis (ie, not daily or scheduled every certain number of hours) and/or initiated <4 weeks prior to day 1.
  • Received the following within 12 hours prior to screening or day 1:

acetaminophen, NSAIDs, tramadol, and/or any narcotic analgesics such as but not limited to hydrocodone, codeine, tramadol, propoxyphene and/or oxycodone (unless in the form of oxycontin). Subject has taken oxycontin within 24 hours prior to screening or day 1.

  • Phase 1b only: Received any herbal medicines (eg St John's wort),or non-vitamin dietary supplements (eg, magnesium) with the exception of calcium within 4 weeks prior to day 1.
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
  • Presence of laboratory abnormalities at screening including the following:

    • Aspartate aminotransferase (AST) or alanine amino transferase (ALT) at screening > 1.5X upper limit of normal (ULN)
    • Serum total bilirubin (TBL) ≥ 1.5 mg/dL (≥ 26 μmol/L)
    • Hemoglobin ≤ 10.5 g/dL(≤105 g/L)
    • Platelet count < 100,000/mm3 (<100 x 109/L)
    • White blood cell count < 2,500 cells/mm3 (2.5 x 109/L)
    • Absolute neutrophil count (ANC) < 1,000/mm3 (1.0 x 109/L)
    • Calculated glomerular filtration rate of ≤ 50 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula
  • Any other laboratory abnormality, which, in the opinion of the investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject.
  • Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 weeks after the last dose of investigational product.
  • Females of child-bearing potential with a positive pregnancy test (assessed by a serum pregnancy test at screening and a urine pregnancy test at baseline).
  • Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 weeks after the last dose of investigational product. Refer to Appendix 5 for additional contraceptive information.
  • Subject has known sensitivity to any of the products or components to be administered during dosing.
  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments [COAs]) to the best of the subject and investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Germany,   Poland,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03410056
Other Study ID Numbers  ICMJE 20170149
2017‐001944‐36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (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 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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 link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP