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Safety Tolerability, and PK of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)

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ClinicalTrials.gov Identifier: NCT03261739
Recruitment Status : Completed
First Posted : August 25, 2017
Last Update Posted : March 14, 2019
Sponsor:
Collaborators:
ProSciento, Inc.
Perspectum
Information provided by (Responsible Party):
Bird Rock Bio, Inc.

Brief Summary:
BRB-018-001 is a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD.

Condition or disease Intervention/treatment Phase
NAFLD Biological: RYI-018 Biological: Placebo Phase 1

Detailed Description:
BRB-018-001 will be conducted as a multicenter, adaptive design, randomized, parallel group study to evaluate the safety, tolerability, and PK of repeat IV doses of RYI-018 in subjects with NAFLD. Subjects in each cohort shall be randomized to either RYI-018 or placebo as weekly injection for four weeks. The active doses of RYI-018 will be as follows: Cohort 1: 0.6 mg/kg, Cohort 2: 1.2 mg/kg, and Cohort 3: 2.5 mg/kg. Primary endpoints include safety and tolerability. Secondary endpoints include pharmacokinetics and immunogenicity.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Randomized, placebo controlled, with 3 sequential cohorts
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind, placebo controlled
Primary Purpose: Treatment
Official Title: An Adaptive Design Study for the Assessment of the Safety, Tolerability, and Pharmacokinetics of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
Actual Study Start Date : August 28, 2017
Actual Primary Completion Date : August 24, 2018
Actual Study Completion Date : August 24, 2018


Arm Intervention/treatment
Experimental: RYI- 018
The doses of RYI-018 to be evaluated in sequential cohorts will be 0.6 mg/kg, 1.2 mg/kg, and 2.5 mg/kg.
Biological: RYI-018
Anti-CB1 monoclonal antibody

Placebo Comparator: Placebo
vehicle control
Biological: Placebo
Placebo




Primary Outcome Measures :
  1. Clinical evaluation of adverse events [ Time Frame: Continuous through 67 days ]
    Subjects will be assessed for adverse events attributable to RYI-018


Secondary Outcome Measures :
  1. Time to peak serum concentration [ Time Frame: Week 1, Week 4 ]
    Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as occurring at tmax.

  2. Peak serum concentration [ Time Frame: Week 1, Week 4 ]
    Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as Cmax.

  3. Area under the serum concentration versus time curve (AUC) [ Time Frame: Week 1, Week 4 ]
    Serum concentrations after single and multiple doses of RYI-018 will be measured and the AUC will be calculated.

  4. Apparent volume of distribution [ Time Frame: Week 1, Week 4 ]
    Serum concentrations after single and multiple doses of RYI-018 will be measured and the apparent volume of distribution, Vz, will be calculated.

  5. Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies. [ Time Frame: Days 8, 15, 22, 29, 36, 67 ]
    Serum samples at multiple timepoints will be collected for quantitation of anti-RYI-018 antibodies.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.
  2. BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).
  3. Liver ultrasound (or transient elastography if approved by medical monitor) which qualitatively shows fatty liver or documented history of NAFLD.
  4. Liver fat percentage by MRI of approximately 10% or greater (MRI to be performed only in subjects with documented NAFLD or fatty liver by ultrasound or transient elastography if approved by medical monitor).
  5. Type 2 diabetes or prediabetes.
  6. Negative urine drug screen/alcohol breath test at screening.
  7. Non-smokers as defined by not smoked any tobacco or nicotine-containing products within 3 months prior to screening. No current use of any nicotine containing product.

Key Exclusion Criteria:

  1. Positive serologic testing for HIV, HBsAg, or HCV.
  2. Have any known malignancy or history of malignancy, except for basal cell or squamous cell skin cancer that has been treated with no evidence of recurrence for at least 3 months prior to Screening.
  3. Have any underlying physical or psychological medical condition that, in the opinion of the Investigator or sponsor, would make it unlikely that the subject will complete the study or is not in the subject's best interest
  4. Liver function tests AST or ALT >5 x ULN at screening. One repeat test may be allowed within 7 days at the discretion of the Investigator.
  5. Total bilirubin > ULN at screening except in patients with a known history of Gilbert's syndrome.
  6. History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
  7. Administration of IP in another trial within 30 Days or 5 times the investigational drug half-life, whichever is longer, prior to the first study drug administration.
  8. History of cerebrovascular event acute coronary syndrome within 6 months of screening.
  9. Any history of seizures, major depression, suicidality, or unexplained syncope.
  10. Subjects with other active (acute or chronic) liver disease other than NAFLD/NASH (e.g., autoimmune liver disease, viral hepatitis, genetic hemochromatosis, Wilson disease, alpha-1-antitrypsin deficiency, alcohol liver disease, drug induced liver disease).
  11. Use of prescription or non-prescription weight loss medications, thiazolidinediones, investigational or approved medications for NASH, or antidepressant medications within 90 days of screening.
  12. Use of insulin injections within 30 days of screening.
  13. History of bariatric surgery or plans for bariatric surgery or an attempt to lose weight during study.
  14. Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day), as per medical history.
  15. Subjects with renal dysfunction estimated glomerular filtration rate <60 mL/min/1.73 m2.
  16. HbA1c >9.5% at screening.
  17. Pregnant or breastfeeding women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03261739


Locations
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United States, California
BRB Site
Chula Vista, California, United States, 91911
United States, Florida
BRB Site
Miami, Florida, United States, 33147
BRB Site
Orlando, Florida, United States, 32804
United States, Texas
BRB Site
San Antonio, Texas, United States, 78215
Australia, Western Australia
BRB Site
Nedlands, Western Australia, Australia, 6009
Canada, Ontario
BRB Site
Toronto, Ontario, Canada, M4G 3E8
Sponsors and Collaborators
Bird Rock Bio, Inc.
ProSciento, Inc.
Perspectum
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Responsible Party: Bird Rock Bio, Inc.
ClinicalTrials.gov Identifier: NCT03261739    
Other Study ID Numbers: BRB-018-001-US
First Posted: August 25, 2017    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bird Rock Bio, Inc.:
NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases