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

NCT03261739 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BRB-018-001-US
• Study Type: interventional
• Target: 84
• Locations: 3 countries
• Sites: 6

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.

Conditions

NAFLD

Keywords

NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Clinical evaluation of adverse events

  Subjects will be assessed for adverse events attributable to RYI-018

  Continuous through 67 days

Secondary Outcomes (5)

• Time to peak serum concentration

  Week 1, Week 4

• Peak serum concentration

  Week 1, Week 4

• Area under the serum concentration versus time curve (AUC)

  Week 1, Week 4

• Apparent volume of distribution

  Week 1, Week 4

• Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.

  Days 8, 15, 22, 29, 36, 67

Study Arms (2)

RYI- 018

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

vehicle control

Biological: Placebo

Interventions

RYI-018 BIOLOGICAL

Anti-CB1 monoclonal antibody

RYI- 018

Placebo BIOLOGICAL

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or females, 18 to 65 years of age (inclusive) at the time of screening.
• BMI ≥25.0 and ≤40.0 (kg/m2) (inclusive).
• Liver ultrasound (or transient elastography if approved by medical monitor) which qualitatively shows fatty liver or documented history of NAFLD.
• 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).
• Type 2 diabetes or prediabetes.
• Negative urine drug screen/alcohol breath test at screening.
• 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.

You may not qualify if:

• Positive serologic testing for HIV, HBsAg, or HCV.
• 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.
• 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
• 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.
• Total bilirubin \> ULN at screening except in patients with a known history of Gilbert's syndrome.
• History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration.
• 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.
• History of cerebrovascular event acute coronary syndrome within 6 months of screening.
• Any history of seizures, major depression, suicidality, or unexplained syncope.
• 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).
• Use of prescription or non-prescription weight loss medications, thiazolidinediones, investigational or approved medications for NASH, or antidepressant medications within 90 days of screening.
• Use of insulin injections within 30 days of screening.
• History of bariatric surgery or plans for bariatric surgery or an attempt to lose weight during study.
• Daily alcohol intake \>20 g/day for women and \>30 g/day for men (on average per day), as per medical history.
• Subjects with renal dysfunction estimated glomerular filtration rate \<60 mL/min/1.73 m2.

Sponsors & Collaborators

• Bird Rock Bio, Inc.: lead
• ProSciento, Inc.: collaborator
• Perspectum: collaborator

Study Sites (6)

BRB Site

Chula Vista, California, 91911, United States

Location

BRB Site

Miami, Florida, 33147, United States

Location

BRB Site

Orlando, Florida, 32804, United States

Location

BRB Site

San Antonio, Texas, 78215, United States

Location

BRB Site

Nedlands, Western Australia, 6009, Australia

Location

BRB Site

Toronto, Ontario, M4G 3E8, Canada

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, placebo controlled, with 3 sequential cohorts

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 25, 2017
• Study Start: August 28, 2017
• Primary Completion: August 24, 2018
• Study Completion: August 24, 2018
• Last Updated: March 14, 2019

Record last verified: 2019-03

Locations

CA (1); US (4); AU (1)