Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04048135
Recruitment Status : Active, not recruiting
First Posted : August 7, 2019
Last Update Posted : August 3, 2021
Sponsor:
Collaborator:
ProSciento
Information provided by (Responsible Party):
89bio, Inc.

Tracking Information
First Submitted Date  ICMJE August 4, 2019
First Posted Date  ICMJE August 7, 2019
Last Update Posted Date August 3, 2021
Actual Study Start Date  ICMJE July 29, 2019
Actual Primary Completion Date August 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Multiple Ascending Dose Study of BIO89-100 in Subjects With Biopsy Confirmed NASH or NAFLD and at High Risk of NASH
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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  ICMJE NASH
Intervention  ICMJE
  • Drug: BIO89-100
    Subcutaneous injection
  • Other: Placebo
    Subcutaneous injection
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 28, 2021)
101
Original Estimated Enrollment  ICMJE
 (submitted: August 6, 2019)
83
Estimated Study Completion Date  ICMJE December 2021
Actual Primary Completion Date August 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04048135
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: Undecided
Responsible Party 89bio, Inc.
Study Sponsor  ICMJE 89bio, Inc.
Collaborators  ICMJE ProSciento
Investigators  ICMJE
Study Director: Charlton, MD 89bio, Inc.
PRS Account 89bio, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP