Clinical trial NCT03261739: Safety Tolerability, and PK of RYI-018 After Repeat Dosing in Subjects With Non-Alcoholic Fatty Liver Disease (NAFLD)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: NAFLD
Keywords: NAFLD, CB1 receptor blockade, anti-CB1 monoclonal antibody
Lead sponsor: Bird Rock Bio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: ProSciento, Inc.
name: Perspectum
First posted: 2017-08-25
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, placebo controlled, with 3 sequential cohorts
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Clinical evaluation of adverse events
timeFrame: Continuous through 67 days
Secondary outcomes:
measure: Time to peak serum concentration
timeFrame: Week 1, Week 4
measure: Peak serum concentration
timeFrame: Week 1, Week 4
measure: Area under the serum concentration versus time curve (AUC)
timeFrame: Week 1, Week 4
measure: Apparent volume of distribution
timeFrame: Week 1, Week 4
measure: Immunogenicity as determined by the concentration of serum anti-RYI-018 antibodies.
timeFrame: Days 8, 15, 22, 29, 36, 67
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: BRB Site
state: California
city: Miami
country: United States
facility: BRB Site
state: Florida
city: Orlando
country: United States
facility: BRB Site
state: Florida
city: San Antonio
country: United States
facility: BRB Site
state: Texas
city: Nedlands
country: Australia
facility: BRB Site
state: Western Australia
city: Toronto
country: Canada
facility: BRB Site
state: Ontario
Study officials:
References: