Clinical trial NCT03060538: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Mellitus, Type 2
Non-Alcoholic Fatty Liver Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AE)
timeFrame: Up to 18 weeks following first dose administration
Secondary outcomes:
measure: Serum BFKB8488A Concentration
timeFrame: On multiple days during treatment period and follow-up (up to 18 weeks following first dose administration)
measure: Change from Baseline in Percentage of Participants with Anti-Therapeutic Antibodies (ATAs)
timeFrame: On multiple days during treatment period and follow-up (up 18 weeks following first dose administration)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group Cullman
state: Alabama
city: Anniston
country: United States
facility: Pinnacle Research Group; Llc, Central
state: Alabama
city: Coronado
country: United States
facility: Southern California Research Center, Inc.
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Tustin
country: United States
facility: Diabetes Research Center
state: California
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Miami
country: United States
facility: Premier Research Associate, Inc
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials
state: Georgia
city: Overland Park
country: United States
facility: MidWest Clinical Research
state: Kansas
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Shelby
country: United States
facility: Carolina Research Center at Jones Family Practice
state: North Carolina
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute, LLC
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes & Endocrine Center
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas Incorporated
state: Texas
city: San Antonio
country: United States
facility: Northeast Clinical Research of San Antonio LLC
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Montreal
country: Canada
facility: inVentiv Health Clinical
state: Quebec
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wong C, Dash A, Fredrickson J, Lewin-Koh N, Chen S, Yoshida K, Liu Y, Gutierrez J, Kunder R. Fibroblast growth factor receptor 1/Klothobeta agonist BFKB8488A improves lipids and liver health markers in patients with diabetes or NAFLD: A phase 1b randomized trial. Hepatology. 2023 Sep 1;78(3):847-862. doi: 10.1002/hep.32742. Epub 2022 Sep 12.