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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

Phase 1
Completed
Conditions
Diabetes Mellitus, Type 2
Non-Alcoholic Fatty Liver Disease
Interventions
Other: Placebo
Registration Number
NCT03060538
Lead Sponsor
Genentech, Inc.
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
154
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive BFKB8488A-matching placebo.
Multiple Ascending Dose BFKB8488ABFKB8488AParticipants 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Adverse Events (AE)Up to 18 weeks following first dose administration

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

Secondary Outcome Measures
NameTimeMethod
Serum BFKB8488A ConcentrationOn 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)On multiple days during treatment period and follow-up (up 18 weeks following first dose administration)

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.

Trial Locations

Locations (18)

MD Clinical

🇺🇸

Hallandale Beach, Florida, United States

MidWest Clinical Research

🇺🇸

Overland Park, Kansas, United States

Premier Research Associate, Inc

🇺🇸

Miami, Florida, United States

inVentiv Health Clinical

🇨🇦

Montreal, Quebec, Canada

Diabetes Research Center

🇺🇸

Tustin, California, United States

Pinnacle Research Group Cullman

🇺🇸

Anniston, Alabama, United States

Agile Clinical Research Trials

🇺🇸

Atlanta, Georgia, United States

Pinnacle Research Group; Llc, Central

🇺🇸

Anniston, Alabama, United States

Southern California Research Center, Inc.

🇺🇸

Coronado, California, United States

Stanford Health Care

🇺🇸

Stanford, California, United States

Dallas Diabetes & Endocrine Center

🇺🇸

Dallas, Texas, United States

Carolina Research Center at Jones Family Practice

🇺🇸

Shelby, North Carolina, United States

Texas Clinical Research Institute, LLC

🇺🇸

Arlington, Texas, United States

Clinical Trials of Texas Incorporated

🇺🇸

San Antonio, Texas, United States

Northeast Clinical Research of San Antonio LLC

🇺🇸

San Antonio, Texas, United States

Consano Clinical Research

🇺🇸

Shavano Park, Texas, United States

Hassman Research Institute

🇺🇸

Berlin, New Jersey, United States

New Orleans Center for Clinical Research

🇺🇸

Knoxville, Tennessee, United States

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