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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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BFKB8488A
Placebo
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pinnacle Research Group Cullman
  • Pinnacle Research Group; Llc, Central
  • Southern California Research Center, Inc.
  • Stanford Health Care
  • Diabetes Research Center
  • MD Clinical
  • Premier Research Associate, Inc
  • Agile Clinical Research Trials
  • MidWest Clinical Research
  • Hassman Research Institute
  • Carolina Research Center at Jones Family Practice
  • New Orleans Center for Clinical Research
  • Texas Clinical Research Institute, LLC
  • Dallas Diabetes & Endocrine Center
  • Clinical Trials of Texas Incorporated
  • Northeast Clinical Research of San Antonio LLC
  • Consano Clinical Research
  • inVentiv Health Clinical

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Multiple Ascending Dose BFKB8488A

Placebo

Arm Description

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.

Participants will receive BFKB8488A-matching placebo.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Serum BFKB8488A Concentration
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.

Full Information

First Posted
February 17, 2017
Last Updated
March 25, 2020
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03060538
Brief Title
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
March 5, 2017 (Actual)
Primary Completion Date
December 13, 2019 (Actual)
Study Completion Date
December 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Non-Alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
154 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Multiple Ascending Dose BFKB8488A
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive BFKB8488A-matching placebo.
Intervention Type
Drug
Intervention Name(s)
BFKB8488A
Other Intervention Name(s)
RO7040551
Intervention Description
Administered subcutaneously starting on Day 1 and according to dosing schedule.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Administered subcutaneously starting on Day 1 and according to dosing schedule.
Primary Outcome Measure Information:
Title
Percentage of Participants with Adverse Events (AE)
Description
An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.
Time Frame
Up to 18 weeks following first dose administration
Secondary Outcome Measure Information:
Title
Serum BFKB8488A Concentration
Time Frame
On multiple days during treatment period and follow-up (up to 18 weeks following first dose administration)
Title
Change from Baseline in Percentage of Participants with Anti-Therapeutic Antibodies (ATAs)
Description
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.
Time Frame
On multiple days during treatment period and follow-up (up 18 weeks following first dose administration)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group Cullman
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Pinnacle Research Group; Llc, Central
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Southern California Research Center, Inc.
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
Stanford Health Care
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Diabetes Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Premier Research Associate, Inc
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Agile Clinical Research Trials
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30328
Country
United States
Facility Name
MidWest Clinical Research
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66209
Country
United States
Facility Name
Hassman Research Institute
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Carolina Research Center at Jones Family Practice
City
Shelby
State/Province
North Carolina
ZIP/Postal Code
28150
Country
United States
Facility Name
New Orleans Center for Clinical Research
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Texas Clinical Research Institute, LLC
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
Dallas Diabetes & Endocrine Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Clinical Trials of Texas Incorporated
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Northeast Clinical Research of San Antonio LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78249
Country
United States
Facility Name
Consano Clinical Research
City
Shavano Park
State/Province
Texas
ZIP/Postal Code
78231
Country
United States
Facility Name
inVentiv Health Clinical
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3X 2H9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35993161
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.
Results Reference
derived

Learn more about this trial

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

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