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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03060538
• Collaborator: (none)
• Enrollment: 154
• Locations: 18
• Arms: 2
• Actual Duration (Months): 33.3
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2; Non-Alcoholic Fatty Liver Disease	Drug: BFKB8488A; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 5, 2017
• Actual Primary Completion Date: Dec 13, 2019
• Actual Study Completion Date: Dec 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multiple Ascending Dose BFKB8488A 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; Administered subcutaneously starting on Day 1 and according to dosing schedule.; Other Names: RO7040551
Placebo Comparator: Placebo Participants will receive BFKB8488A-matching placebo.	Other: Placebo; Administered subcutaneously starting on Day 1 and according to dosing schedule.

Outcome Measures

Primary Outcome Measures

1. 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

1. Serum BFKB8488A Concentration [On multiple days during treatment period and follow-up (up to 18 weeks following first dose administration)]

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group Cullman	Anniston	Alabama	United States	36207
2	Pinnacle Research Group; Llc, Central	Anniston	Alabama	United States	36207
3	Southern California Research Center, Inc.	Coronado	California	United States	92118
4	Stanford Health Care	Stanford	California	United States	94305
5	Diabetes Research Center	Tustin	California	United States	92780
6	MD Clinical	Hallandale Beach	Florida	United States	33009
7	Premier Research Associate, Inc	Miami	Florida	United States	33165
8	Agile Clinical Research Trials	Atlanta	Georgia	United States	30328
9	MidWest Clinical Research	Overland Park	Kansas	United States	66209
10	Hassman Research Institute	Berlin	New Jersey	United States	08009
11	Carolina Research Center at Jones Family Practice	Shelby	North Carolina	United States	28150
12	New Orleans Center for Clinical Research	Knoxville	Tennessee	United States	37920
13	Texas Clinical Research Institute, LLC	Arlington	Texas	United States	76012
14	Dallas Diabetes & Endocrine Center	Dallas	Texas	United States	75230
15	Clinical Trials of Texas Incorporated	San Antonio	Texas	United States	78229
16	Northeast Clinical Research of San Antonio LLC	San Antonio	Texas	United States	78249
17	Consano Clinical Research	Shavano Park	Texas	United States	78231
18	inVentiv Health Clinical	Montreal	Quebec	Canada	H3X 2H9

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03060538
• Other Study ID Numbers: GC39547
• First Posted: Feb 23, 2017
• Last Update Posted: Mar 27, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Mar 27, 2020