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

Primary Purpose

NASH

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BIO89-100

Placebo

About this trial

This is an interventional treatment trial for NASH focused on measuring NASH, NAFLD, Liver diseases, Fatty Liver, Metabolic diseases

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Dose 1

Dose 2

Dose 3

Dose 4

Dose 5

Dose 6

Placebo

Dose 4 Open Label

Arm Description

Outcomes

Primary Outcome Measures

Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of subjects who discontinued due to AEs and due to related AEs

To characterize the BIO89-100 Pharmacokinetics (PK) by Peak Plasma Concentration

To characterize the BIO89-100 PK by Time to Peak Plasma Concentration (Tmax)

To characterize the BIO89-100 PK by Area under the plasma concentration versus time curve (AUC)

To characterize the BIO89-100 PK by the terminal elimination half-life (t1/2)

To characterize effect of BIO89-100 on liver histology by Improvement in NAS score

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

Secondary Outcome Measures

Percentage change from baseline in Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

Percentage change from baseline in triglycerides

Percentage change from baseline in Low Density Lipoprotein (LDL) Cholesterol

Percentage change from baseline in Alanine Transaminase (ALT)

Percentage change from baseline in N-terminal type III collagen propeptide (Pro-C3)

Assessment of the incidence and characteristics of anti drug antibodies (ADA) developed against BIO89-100 after dosing

To characterize effect of BIO89-100 on liver histology by improvement of fibrosis

Improvement of fibrosis ≥1 stage without worsening of NASH

To characterize effect of BIO89-100 on liver histology by NASH resolution

NASH resolution without worsening of fibrosis

Full Information

NCT ID

NCT04048135

First Posted

August 4, 2019

Last Updated

November 28, 2022

Sponsor

89bio, Inc.

Collaborators

ProSciento, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04048135

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

July 29, 2019 (Actual)

Primary Completion Date

August 28, 2020 (Actual)

Study Completion Date

January 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

89bio, Inc.

Collaborators

ProSciento, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NASH

Keywords

NASH, NAFLD, Liver diseases, Fatty Liver, Metabolic diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Masking Description

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

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose 1

Arm Type

Experimental

Arm Title

Dose 2

Arm Type

Experimental

Arm Title

Dose 3

Arm Type

Experimental

Arm Title

Dose 4

Arm Type

Experimental

Arm Title

Dose 5

Arm Type

Experimental

Arm Title

Dose 6

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

Dose 4 Open Label

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

BIO89-100

Intervention Description

Subcutaneous injection

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Subcutaneous injection

Primary Outcome Measure Information:

Title

Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame

Part 1-16 weeks, Part 2-23 weeks

Title

Number of subjects who discontinued due to AEs and due to related AEs

Time Frame

Part 1 only-16 weeks

Title

To characterize the BIO89-100 Pharmacokinetics (PK) by Peak Plasma Concentration

Time Frame

Part 1 only-13 weeks

Title

To characterize the BIO89-100 PK by Time to Peak Plasma Concentration (Tmax)

Time Frame

Part 1 only-13 weeks

Title

To characterize the BIO89-100 PK by Area under the plasma concentration versus time curve (AUC)

Time Frame

Part 1 only-13 weeks

Title

To characterize the BIO89-100 PK by the terminal elimination half-life (t1/2)

Time Frame

Part 1 only-13 weeks

Title

To characterize effect of BIO89-100 on liver histology by Improvement in NAS score

Description

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

Time Frame

Part 2 only-20 weeks

Secondary Outcome Measure Information:

Title

Percentage change from baseline in Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)

Time Frame