Study to Explore the Efficacy and Safety of BIO89-100 in Subjects With Severe Hypertriglyceridemia

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Explore the Efficacy and Safety of BIO89-100 in Subjects With Severe Hypertriglyceridemia

This study is designed to assess the efficacy, safety, and tolerability of different doses and dose regimens (QW or every 2 weeks [Q2W]), subcutaneous (SC) dosing of BIO89-100 compared to placebo in subjects with Severe Hypertriglyceridemia (SHTG).

Study Overview

• Status: Completed
• Conditions: Severe Hypertriglyceridemia
• Intervention / Treatment: Drug: Placebo; Drug: BIO89-100

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Pardubice, Czechia, 530 02
    • 89bio Clinical Study Site
  • Prague, Czechia, 100 00
    • 89bio Clinical Study Site
  • Prague, Czechia, 150 00
    • 89bio Clinical Study Site
  • Prague, Czechia, 158 00
    • 89bio Clinical Study Site
  • Praha 4, Czechia, 14021
    • 89bio Clinical Study Site
• Hungary
  • Baja, Hungary
    • 89bio Clinical Study Site
  • Budapest, Hungary, 1032
    • 89bio Clinical Study Site
  • Békéscsaba, Hungary, 5600
    • 89bio Clinical Study Site
  • Debrecen, Hungary, 4032
    • 89bio Clinical Study Site
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • 89bio Clinical Study Site
• Poland
  • Białystok, Poland, 15-351
    • 89bio Clinical Study Site
  • Białystok, Poland, 15-879
    • 89bio Clinical Study Site
  • Lodz, Poland, 93-338
    • 89bio Clinical Study Site
  • Oswiecim, Poland, 32-600
    • 89bio Clinical Study Site
  • Rzeszów, Poland, 35-055
    • 89bio Clinical Study Site
  • Toruń, Poland, 87-100
    • 89bio Clinical Study Site
• United States
  • California
    • La Mesa, California, United States, 91942
      • 89bio Clinical Study Site
    • San Francisco, California, United States, 94158
      • 89bio Clinical Study Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • 89bio Clinical Study Site
    • Greenacres City, Florida, United States, 33467
      • 89bio Clinical Study Site
    • Jacksonville, Florida, United States, 32205
      • 89bio Clinical Study Site
    • Miami, Florida, United States, 33125
      • 89bio Clinical Study Site
    • Miami, Florida, United States, 33135
      • 89bio Clinical Study Site
    • Miami Lakes, Florida, United States, 33014
      • 89bio Clinical Study Site
    • Miami Lakes, Florida, United States, 33016
      • 89bio Clinical Study Site
    • North Miami Beach, Florida, United States, 33162
      • 89bio Clinical Study Site
    • Orlando, Florida, United States, 32825
      • 89bio Clinical Study Site
    • Tampa, Florida, United States, 33606
      • 89bio Clinical Study Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • 89bio Clinical Study Site
  • Illinois
    • Quincy, Illinois, United States, 62301
      • 89bio Clinical Study Site
    • Wauconda, Illinois, United States, 60084
      • 89bio Clinical Study Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • 89bio Clinical Study Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • 89bio Clinical Study Site
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • 89bio Clinical Study Site
  • New York
    • Albany, New York, United States, 12203
      • 89bio Clinical Study Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • 89bio Clinical Study Site
    • Morganton, North Carolina, United States, 28655
      • 89bio Clinical Study Site
  • Ohio
    • Marion, Ohio, United States, 43303
      • 89bio Clinical Study Site
  • South Carolina
    • Summerville, South Carolina, United States, 29435
      • 89bio Clinical Study Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • 89bio Clinical Study Site
    • Kingsport, Tennessee, United States, 37660
      • 89bio Clinical Study Site
  • Texas
    • Austin, Texas, United States, 78705
      • 89bio Clinical Study Site
    • Dallas, Texas, United States, 75204
      • 89bio Clinical Study Site
    • Dallas, Texas, United States, 77365
      • 89bio Clinical Study Site
    • Houston, Texas, United States, 77089
      • 89bio Clinical Study Site
    • Lampasas, Texas, United States, 76550
      • 89bio Clinical Study Site
    • Magnolia, Texas, United States, 77355
      • 89bio Clinical Study Site
  • Virginia
    • Manassas, Virginia, United States, 20110
      • 89bio Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female age ≥21 to ≤75 years.
2. Screening fasting triglyceride ≥500 mg/dL and ≤2000 mg/dL.
3. Willing to follow a lifestyle for optimal control of TGs and disease management during the study.
4. Patients could be taking statins and/or prescription fish oil as background therapy OR not be taking any background therapy.
5. MRI-PDFF of ≥6% for subjects screened for the fibrate expansion cohort.

Exclusion Criteria:

1. Uncontrolled or newly diagnosed hypertension.
2. Body mass index (BMI) >45 kg/m2.
3. Receiving niacin, PCSK9 inhibitors, or supplements that could lower lipid levels.
4. Type 1 diabetes mellitus (T1DM).
5. Diagnosis of Type 2 diabetes mellitus (T2DM) <6 months prior to screening.
6. History of malignancy within 5 years prior to screening.
7. Subjects with known lipoprotein lipase impairment or deficiency (Fredrickson Type 1), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type 3).
8. Clinically or otherwise documented cardiovascular or cerebrovascular disease.
9. Weight change ≥5% in 3 months prior to screening visit 1 or weight change ≥5% during screening or planning to try to lose weight during conduct of study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Main Study; The cohort will include subjects with SHTG without concurrent fibrate therapy and will consist of 5 treatment groups to compare 4 dose levels/regimens of BIO89-100 versus placebo.	Drug: Placebo; Placebo; Drug: BIO89-100; BIO89-100
ACTIVE_COMPARATOR: Fibrate Expansion Study; The cohort will include subjects with SHTG on stable background fibrate therapy and with a baseline MRI PDFF ≥6%, and will consist of 2 treatment groups comparing one dose regimen of BIO89 100 versus placebo.	Drug: Placebo; Placebo; Drug: BIO89-100; BIO89-100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum TG	Percentage change in TG levels in subjects with SHTG (TG ≥500) mg/dL) from baseline	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieve TG <500 mg/dL	Proportion of subjects whose TG level is reduced to below 500 mg/dL levels	Week 8
Very low-density lipoprotein cholesterol (VLDL-C)	Percentage change from baseline	Week 8
Low-density lipoprotein cholesterol (LDL-C)	Percentage change from baseline	Week 8
Non-high-density lipoprotein cholesterol (non-HDL-C)	Percentage change from baseline	Week 8
High-density lipoprotein cholesterol (HDL-C)	Percentage change from baseline	Week 8
Very low-density lipoprotein triglycerides (VLDL-TG)	Percentage change from baseline	Week 8
Apolipoprotein B100 (ApoB)	Percentage change from baseline	Week 8
Remnant lipoprotein cholesterol (RLP-C)	Percentage change from baseline	Week 8
high-sensitivity C-reactive protein (hsCRP)	Percentage change from baseline	Week 8
Fasting plasma glucose	Percentage change in metabolic markers from baseline	Week 8
Fasting adiponectin	Percentage change in metabolic markers from baseline	Week 8
Fasting plasma body weight	Percentage change in metabolic markers from baseline	Week 8
Serum BIO89-100 concentration	Characterize PK parameters	Week 8
Maximal observed serum concentrations (Cmax)	PK parameters in Intensive PK subgroup	Week 8
Area under the serum drug concentration	PK parameters in Intensive PK subgroup	Week 8
Time to achieve Cmax (tmax)	PK parameters in Intensive PK subgroup	Week 8
Terminal elimination half-life (t1⁄2)	PK parameters in Intensive PK subgroup	Week 8
Liver Proton Density Fat Fraction (MRI-PDFF)	Percentage change in hepatic steatosis from baseline	Week 8

Collaborators and Investigators

• Sponsor: 89bio, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2020
• Primary Completion (ACTUAL): May 19, 2022
• Study Completion (ACTUAL): May 31, 2022

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (ACTUAL): September 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Dyslipidemia; FGF21; Hypertriglyceridemia; Lipid disorder
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia
• Other Study ID Numbers: BIO89-100-221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No