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

NAFLD Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03261739
• Other study ID #: BRB-018-001-US
• Status: Completed
• Phase: Phase 1
• Start date: August 28, 2017
• Est. completion date: August 24, 2018

Study information

• Verified date: March 2019
• Source: Bird Rock Bio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: August 24, 2018
• Est. primary completion date: August 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• NAFLD
• Non-alcoholic Fatty Liver Disease

Intervention

Biological:
• RYI-018
Anti-CB1 monoclonal antibody
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	BRB Site	Nedlands	Western Australia
Canada	BRB Site	Toronto	Ontario
United States	BRB Site	Chula Vista	California
United States	BRB Site	Miami	Florida
United States	BRB Site	Orlando	Florida
United States	BRB Site	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Bird Rock Bio, Inc.	Perspectum Diagnostics Ltd, ProSciento, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical evaluation of adverse events	Subjects will be assessed for adverse events attributable to RYI-018	Continuous through 67 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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