A Multiple Ascending Dose Study to Evaluate Safety and Tolerability of BFKB8488A in Participants With Type 2 Diabetes Mellitus and Participants With Non-Alcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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This is a Phase Ib, randomized, blinded, placebo-controlled, multiple ascending-dose study of the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of BFKB8488A in participants with Type 2 diabetes mellitus (T2DM) and participants with non-alcoholic fatty liver disease(NAFLD). A maximum of approximately 160 participants will be enrolled across multiple sites in the United States. Participants will be randomly assigned to receive study drug (active BFKB8488A or placebo). The study will consist of a screening period (up to 8 weeks), a 12-week treatment period, and a 6-week follow-up period. Participants may come to clinic for an optional pre-screening visit.

Official Title
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A Phase Ib, Randomized, Blinded, Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Subcutaneous BFKB8488A in Patients With Type 2 Diabetes Mellitus and Patients With Non-Alcoholic Fatty Liver Disease

Conditions
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Diabetes Mellitus, Type 2, Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: BFKB8488A
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For T2DM Cohort only: Body mass index (BMI) ≥ 27 kg/m2 and ≤ 40 kg/m2. A confirmed diagnosis of Type 2 diabetes ≥ 6 months at screening Current stable treatment (at least 3 months) for diabetes Hemoglobin A1c (HbA1c) ≥ 6.8% and ≤ 9.0%. For women of childbearing potential, agreement to remain abstinent or use reliable contraception during treatment period and for at least 42 days after last dose of study drug For men, agreement to remain abstinent or use reliable contraception and agree to refrain from donating sperm For NAFLD cohort only: BMI ≥ 25 kg/m2 and ≤ 40 kg/m2 At screening, confirmed liver fat by ultrasound OR calculated Liver Fat ≥ 10% using variables from the NAFLD liver fat score Hepatic steatosis on magnetic resonance imaging (MRI; ≥ 10% average liver proton density fat fraction [PDFF]) prior to randomization. Exclusion Criteria: Pregnant, lactating, or intending to become pregnant within 42 days after the last dose of study drug is administered Suspected or confirmed diagnosis of Type 1 diabetes Significant cardiac disease Any psychiatric illness that increases the risk of participation in the study History of severe allergic, anaphylactic, or other hypersensitivity reactions, or severe systemic bacterial, fungal, or parasitic infections Poor peripheral venous access Received blood products within 2 months before dosing Donation or loss of blood within 30-56 days prior to study drug administration Positive for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV) antibody Liver enzymes greater than acceptable limits History of eating disorders or surgical procedures for weight loss Active participation in a structured weight loss or dietary program Treatment with investigational therapy or exposure to any biological therapy Illicit drug use, marijuana use, or alcohol abuse Current use of more than one pack of cigarettes a day or equivalent nicotine- containing products Any serious medical condition or abnormality in clinical laboratory tests

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiple Ascending Dose BFKB8488A<br>Participants will be randomized to receive BFKB8488A. When adequate safety data are available, a review will be done for all participants to make a dose-escalation or dose and/or regimen modification decision. This will be repeated for each cohort. | Drug: BFKB8488A<br>* Administered subcutaneously starting on Day 1 and according to dosing schedule.<br>* Other names: RO7040551;|
| Placebo Comparator: Placebo<br>Participants will receive BFKB8488A-matching placebo. | Other: Placebo<br>* Administered subcutaneously starting on Day 1 and according to dosing schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AE) | An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. | Up to 18 weeks following first dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum BFKB8488A Concentration |  | On multiple days during treatment period and follow-up (up to 18 weeks following first dose administration) | 
| Change from Baseline in Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) | Participants are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and at least one post-baseline samples if above acceptable limits. The number and percentage of ATA-positive and ATA-negative participants will be summarized by treatment group. | On multiple days during treatment period and follow-up (up 18 weeks following first dose administration) |