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

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)

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.

Study Overview

• Status: Completed
• Conditions: NAFLD
• Intervention / Treatment: Biological: RYI-018; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • BRB Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4G 3E8
      • BRB Site
• United States
  • California
    • Chula Vista, California, United States, 91911
      • BRB Site
  • Florida
    • Miami, Florida, United States, 33147
      • BRB Site
    • Orlando, Florida, United States, 32804
      • BRB Site
  • Texas
    • San Antonio, Texas, United States, 78215
      • BRB Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical evaluation of adverse events	Subjects will be assessed for adverse events attributable to RYI-018	Continuous through 67 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak serum concentration	Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as occurring at tmax.	Week 1, Week 4
Peak serum concentration	Serum concentrations after single and multiple doses of RYI-018 will be measured and the highest concentration will be identified as Cmax.	Week 1, Week 4
Area under the serum concentration versus time curve (AUC)	Serum concentrations after single and multiple doses of RYI-018 will be measured and the AUC will be calculated.	Week 1, Week 4
Apparent volume of distribution	Serum concentrations after single and multiple doses of RYI-018 will be measured and the apparent volume of distribution, Vz, will be calculated.	Week 1, Week 4
Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.	Serum samples at multiple timepoints will be collected for quantitation of anti-RYI-018 antibodies.	Days 8, 15, 22, 29, 36, 67

Collaborators and Investigators

• Sponsor: Bird Rock Bio, Inc.
• Collaborators: Perspectum; ProSciento, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2017
• Primary Completion (Actual): August 24, 2018
• Study Completion (Actual): August 24, 2018

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: March 13, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: BRB-018-001-US

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No