A Multiple Ascending Dose Study of BIO89-100 in Subjects With Biopsy Confirmed NASH or NAFLD and at High Risk of NASH

• ClinicalTrials.gov Identifier: NCT04048135
• Recruitment Status: Active, not recruiting
• First Posted: August 7, 2019
• Last Update Posted: August 3, 2021
• Sponsor: 89bio, Inc.
• Collaborator: ProSciento
• Information provided by (Responsible Party): 89bio, Inc.

Tracking Information

• First Submitted Date: August 4, 2019
• First Posted Date: August 7, 2019
• Last Update Posted Date: August 3, 2021
• Actual Study Start Date: July 29, 2019
• Actual Primary Completion Date: August 28, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2021)

• Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Part 1-16 weeks, Part 2-23 weeks ]
• Number of subjects who discontinued due to AEs and due to related AEs [ Time Frame: Part 1 only-16 weeks ]
• To characterize the BIO89-100 Pharmacokinetics (PK) by Peak Plasma Concentration [ Time Frame: Part 1 only-13 weeks ]
• To characterize the BIO89-100 PK by Time to Peak Plasma Concentration (Tmax) [ Time Frame: Part 1 only-13 weeks ]
• To characterize the BIO89-100 PK by Area under the plasma concentration versus time curve (AUC) [ Time Frame: Part 1 only-13 weeks ]
• To characterize the BIO89-100 PK by the terminal elimination half-life (t1/2) [ Time Frame: Part 1 only-13 weeks ]
• To characterize effect of BIO89-100 on liver histology by Improvement in NAS score [ Time Frame: Part 2 only-20 weeks ]
  At least a 2-point improvement in NAFLD Activity Score (NAS) with at least a 1 point improvement in ballooning or lobular inflammation, and no worsening of fibrosis

Original Primary Outcome Measures (submitted: August 6, 2019)

• Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 16 weeks ]
• Number of subjects who discontinued due to AEs and due to related AEs [ Time Frame: 16 weeks ]
• To characterize the BIO89-100 Pharmacokinetics (PK) by Peak Plasma Concentration [ Time Frame: 13 weeks ]
• To characterize the BIO89-100 PK by Time to Peak Plasma Concentration (Tmax) [ Time Frame: 13 weeks ]
• To characterize the BIO89-100 PK by Area under the plasma concentration versus time curve (AUC) [ Time Frame: 13 weeks ]
• To characterize the BIO89-100 PK by the terminal elimination half-life (t1/2) [ Time Frame: 13 weeks ]

Current Secondary Outcome Measures (submitted: July 28, 2021)

• Percentage change from baseline in Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) [ Time Frame: Part 1-13 weeks, Part 2-20 weeks ]
• Percentage change from baseline in triglycerides [ Time Frame: Part 1-13 weeks, Part 2-20 weeks ]
• Percentage change from baseline in Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: Part 1-13 weeks, Part 2-20 weeks ]
• Percentage change from baseline in Alanine Transaminase (ALT) [ Time Frame: Part 1-13 weeks, Part 2-20 weeks ]
• Percentage change from baseline in N-terminal type III collagen propeptide (Pro-C3) [ Time Frame: Part 1-13 weeks, Part 2-20 weeks ]
• Assessment of the incidence and characteristics of anti drug antibodies (ADA) developed against BIO89-100 after dosing [ Time Frame: Part 1-16 week, Part 2-24 weeks ]
• To characterize effect of BIO89-100 on liver histology by improvement of fibrosis [ Time Frame: Part 2 only-20 weeks ]
  Improvement of fibrosis ≥1 stage without worsening of NASH
• To characterize effect of BIO89-100 on liver histology by NASH resolution [ Time Frame: Part 2 only-20 weeks ]
  NASH resolution without worsening of fibrosis

Original Secondary Outcome Measures (submitted: August 6, 2019)

• Percentage change from baseline in Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) [ Time Frame: 13 weeks ]
• Percentage change from baseline in triglycerides [ Time Frame: 13 weeks ]
• Percentage change from baseline in Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: 13 weeks ]
• Percentage change from baseline in Alanine Transaminase (ALT) [ Time Frame: 13 weeks ]
• Percentage change from baseline in N-terminal type III collagen propeptide (Pro-C3) [ Time Frame: 13 weeks ]
• Assessment of the incidence and characteristics of anti drug antibodies (ADA) developed against BIO89-100 after dosing [ Time Frame: 16 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multiple Ascending Dose Study of BIO89-100 in Subjects With Biopsy Confirmed NASH or NAFLD and at High Risk of NASH
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of BIO89-100 Administered Subcutaneously in Subjects With Nonalcoholic Steatohepatitis (NASH) or With Nonalcoholic Fatty Liver Disease (NAFLD) and at High Risk of NASH

Brief Summary

Part 1: This is a multi-center evaluation of BIO89-100 (administered weekly or every other week) in a randomized, double-blind, placebo-controlled study administered for 12 weeks in subjects with NASH and NAFLD at high risk of NASH, including a pre-defined number of subjects with biopsy confirmed NASH and fibrosis stages F1-F3 to be enrolled

Part 2: This is a multi-center, open label evaluation of BIO89-100 at 27 mg administered weekly for 20 weeks in subjects with biopsy-poven NASH (NAS ≥4, fibrosis stage F2 or F3)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Cohorts 1-6 is blinded, Cohort 7 is open label

Primary Purpose: Treatment

• Condition: NASH

Intervention

• Drug: BIO89-100
  Subcutaneous injection
• Other: Placebo
  Subcutaneous injection

Study Arms

• Experimental: Dose 1
  Intervention: Drug: BIO89-100
• Experimental: Dose 2
  Intervention: Drug: BIO89-100
• Experimental: Dose 3
  Intervention: Drug: BIO89-100
• Experimental: Dose 4
  Intervention: Drug: BIO89-100
• Experimental: Dose 5
  Intervention: Drug: BIO89-100
• Experimental: Dose 6
  Intervention: Drug: BIO89-100
• Placebo Comparator: Placebo
  Intervention: Other: Placebo
• Experimental: Dose 4 Open Label
  Intervention: Drug: BIO89-100

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 28, 2021): 101
• Original Estimated Enrollment (submitted: August 6, 2019): 83
• Estimated Study Completion Date: December 2021
• Actual Primary Completion Date: August 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Subjects must be 21 to 75 years of age inclusive, at the time of signing the informed consent form (ICF).
• Evidence of steatosis by Fibroscan and MRI-PDFF
• NASH or NAFLD at high risk for NASH as reflected by AT LEAST ONE of the following:
• Diagnosis of NASH with fibrosis (stages F1, F2 or F3), without cirrhosis, by percutaneous liver biopsy within 24 months prior to screening
• Central obesity WITH T2DM
• Central obesity WITH either increased ALT and/or Fibroscan VCTE score ≥7 KPa.
• Part 2 only: Biopsy-proven NASH in a liver biopsy obtained within 24 weeks of baseline with fibrosis stage F2 or F3 and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. A small number of high risk F1 allowed.

Key Exclusion Criteria:

• Clinically significant disorder or a history of any illness that, in the opinion of the Investigator, might confound the results of the study, or pose additional risk to the subject by participation in the study.
• History of type 1 diabetes.
• Weight loss of more than 5% within 3 months prior to Day -1 or more than 10% within 6 months prior to Day -1 or planning to try to lose weight during conduct of study.
• History of a liver disorder other than NASH or clinical suspicion of a liver disorder other than NASH
• History of cirrhosis or evidence of cirrhosis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT04048135
• Other Study ID Numbers: BIO89-100-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: 89bio, Inc.
• Study Sponsor: 89bio, Inc.
• Collaborators: ProSciento

Investigators

• Study Director: Charlton, MD; 89bio, Inc.

• PRS Account: 89bio, Inc.
• Verification Date: July 2021