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Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With 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: NCT02176876
Recruitment Status : Completed
First Posted : June 27, 2014
Last Update Posted : June 29, 2015
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE June 25, 2014
First Posted Date  ICMJE June 27, 2014
Last Update Posted Date June 29, 2015
Study Start Date  ICMJE August 2014
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
Incidence of adverse events, changes in laboratory tests and vital signs from baseline, and development of immunogenicity after dosing [ Time Frame: Up to 100 days ]
This composite endpoint will measure the safety and tolerability profile of GS-5745.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2014)
PK profile of GS-5745 [ Time Frame: Pre-infusion, 30 minutes, 4 hours, and 24 hours post-infusion on Day 1; pre-infusion and 30 minutes post-infusion on Days 15 and 29; Days 4, 8, 36, and 43 ]
This composite endpoint will measure the plasma PK profile of GS-5745. The following parameters will be measured, where applicable:
  • Cmax: maximum observed concentration of drug in plasma
  • Tmax: time of Cmax
  • Clast: last observable concentration of drug
  • Tlast: time of Clast
  • AUClast: concentration of drug from time zero to the last quantifiable concentration
  • AUCinf: concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time)
  • AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
  • Ctau: observed drug concentration at the end of the dosing interval
  • λz: terminal elimination rate constant
  • CL: systemic clearance of the drug following intravenous administration
  • Vz: volume of distribution of the drug following intravenous administration
Original Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2014)
Plasma PK parameters of GS-5745 (where applicable) as measured by Cmax, Tmax, Clast, Tlast, AUClast, AUCinf, AUCtau, Ctau, λz, CL, and Vz [ Time Frame: Pre-infusion, 30 minutes, 4 hours, and 24 hours post-infusion on Day 1; pre-infusion and 30 minutes post-infusion on Days 15 and 29; Days 4, 8, 36, and 43 ]
  • Cmax is defined as the maximum observed concentration of drug in plasma
  • Tmax is defined as the time of Cmax
  • Clast is defined as the last observable concentration of drug
  • Tlast is defined as the time of Clast
  • AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration
  • AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time)
  • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
  • Ctau is defined as the observed drug concentration at the end of the dosing interval
  • λz is defined as the terminal elimination rate constant
  • CL is defined as the systemic clearance of the drug following intravenous administration
  • Vz is defined as the volume of distribution of the drug following intravenous administration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With Rheumatoid Arthritis
Official Title  ICMJE A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety, Tolerability, and Pharmacokinetics of GS-5745 in Subjects With Rheumatoid Arthritis
Brief Summary This study is to assess the safety, tolerability, and pharmacokinetics (PK) of multiple infusions of GS-5745 in adults with rheumatoid arthritis (RA). Participants will be randomized in a 4:1 ratio to receive 1 intravenous (IV) infusion of GS-5745 or placebo every 2 weeks, for a total of 3 IV infusions.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: GS-5745
    GS-5745 400 mg administered intravenously
  • Drug: Placebo to match GS-5745
    Placebo to match GS-5745 administered intravenously
Study Arms  ICMJE
  • Experimental: GS-5745
    Participants will receive GS-5745 every 2 weeks for a total of 3 infusions.
    Intervention: Drug: GS-5745
  • Placebo Comparator: Placebo to match GS-5745
    Participants will receive placebo to match GS-5745 every 2 weeks for a total of 3 infusions.
    Intervention: Drug: Placebo to match GS-5745
Publications * Gossage DL, Cieslarova B, Ap S, Zheng H, Xin Y, Lal P, Chen G, Smith V, Sundy JS. Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis. Clin Ther. 2018 Jan;40(1):156-165.e5. doi: 10.1016/j.clinthera.2017.11.011. Epub 2017 Dec 26.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: April 29, 2015)
18
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2014)
20
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 to 70 years of age, inclusive, at time of screening
  • Weight: ≥ 45 to < 120 kg
  • Males or non-pregnant, non-lactating females
  • Diagnosis of RA according to the 1987 revised American College of Rheumatology (ACR) for the classification of RA
  • Active disease, defined as a mean high sensitivity C-reactive protein (hsCRP) value from Visits 1 & 2 of ≥ 8 mg/L
  • Individuals taking chronic Disease-Modifying Antirheumatic Drugs (DMARDs) should be on a stable dose for at least 45 days prior to randomization
  • Chronic use of systemic corticosteroids up to a maximum of 10 mg/day of prednisone or equivalent is allowed if dose is stable for at least 30 days prior to randomization
  • Nonsteroidal Anti-inflammatory Drugs (NSAIDs) or other analgesics are allowed if doses are stable for at least 30 days prior to randomization

Exclusion Criteria:

  • Have a document medical history of anaphylaxis
  • Positive HIV antibody during screening
  • Positive hepatitis B surface antigen (HBsAg), or positive hepatitis B core antigen (HBcAg), followed by a positive hepatitis B virus (HBV) DNA by quantitative polymerase chain reaction (PCR) during screening
  • Positive hepatitis C virus (HCV) antibody followed by a positive HCV viral RNA during screening
  • A positive QuantiFERON-tuberculosis (TB) GOLD test during screening
  • History of malignancy within the last 5 years except for individuals who have been treated locally for non-melanoma skin cancer or cervical carcinoma in situ
  • Severe dementia or Alzheimer's disease, chronic medical or psychiatric problem, or alcohol or drug abuse, that in the judgment of the investigator may interfere with individual's ability to comply with study procedures
  • Any serious cardiac event such as myocardial infarction, unstable or life-threatening arrhythmia, hospitalization for cardiac failure within 6 months prior to randomization or any significant or new ECG finding at Visit 1 as judged by the investigator
  • History of significant systemic involvement secondary to RA such as vasculitis, pulmonary fibrosis, or Felty's syndrome
  • History of or current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease
  • History of or current autoimmune or rheumatic disorders, other than RA, such as systemic lupus erythematosus, inflammatory bowel disease, fibromyalgia, polymyalgia rheumatic, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome
  • Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the judgment of the investigator, would make the individual unsuitable for the study or would prevent compliance with the study protocol
  • Treatment with antibiotics for a clinical infection or other medical condition within 30 days prior to randomization
  • Treatment with azathioprine or cyclosporine 90 days prior to randomization
  • Treatment with infliximab, golimumab, adalimumab, abatacept, tocilizumab within 90 days; and etanercept or anakinra within 30 days of randomization
  • Treatment with rituximab or any B-cell depleting agent within 12 months of randomization
  • Treatment with any other marketed or investigational biologic within 5 half-lives of the molecule or if unknown within 90 days of randomization
  • Administration of any investigational drug or use of any investigational device within 30 days prior to randomization
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czech Republic,   Hungary
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02176876
Other Study ID Numbers  ICMJE GS-US-373-1276
2013-005396-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Gilead Sciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Gilead Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: David Gossage, MD Gilead Sciences
PRS Account Gilead Sciences
Verification Date June 2015

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