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

Study Overview
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Brief Summary
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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).

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

Conditions
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Severe Hypertriglyceridemia

Intervention / Treatment
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* Drug: BIO89-100
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age ≥21 to ≤75 years. Screening fasting triglyceride ≥500 mg/dL and ≤2000 mg/dL. Willing to follow a lifestyle for optimal control of TGs and disease management during the study. Patients could be taking statins and/or prescription fish oil as background therapy OR not be taking any background therapy. MRI-PDFF of ≥6% for subjects screened for the fibrate expansion cohort. Exclusion Criteria: Uncontrolled or newly diagnosed hypertension. Body mass index (BMI) >45 kg/m2. Receiving niacin, PCSK9 inhibitors, or supplements that could lower lipid levels. Type 1 diabetes mellitus (T1DM). Diagnosis of Type 2 diabetes mellitus (T2DM) <6 months prior to screening. History of malignancy within 5 years prior to screening. Subjects with known lipoprotein lipase impairment or deficiency (Fredrickson Type 1), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type 3). Clinically or otherwise documented cardiovascular or cerebrovascular disease. 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Main Study<br>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: BIO89-100<br>* BIO89-100<br>Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Fibrate Expansion Study<br>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: BIO89-100<br>* BIO89-100<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FGF21, Hypertriglyceridemia, Dyslipidemia, Lipid disorder