First-In-Human Study of GFB-024 in Healthy Overweight and Obese Participants, and Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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GFB-024 is intended for use in patients with kidney disease such as diabetic nephropathy. This study is the first time GFB-024 has been used in humans. The first part of the study will assess the safety of a single dose of GFB-024 in healthy overweight and obese volunteers and the effect of GFB-024 on the body as compared to an inactive placebo medication. The second part of the study will assess the safety of repeated doses of GFB-024 in participants with Type 2 diabetes and the effect of GFB-024 on the body as compared to an inactive placebo medication.

Detailed Description
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This is a first-in-human study. It is intended to provide the initial safety, pharmacokinetics (PK), and pharmacology data for GFB-024 in humans. This study will comprise a single ascending dose (SAD) escalation component in healthy overweight and obese volunteer participants and a repeat-dose component to confirm repeat-dose safety, tolerability, PK, and immunogenicity in participants with Type 2 diabetes mellitus. It will also explore potential cannabinoid-1 receptor (CB1) activity, participant selection, pharmacodynamics, and differential response biomarkers.

Official Title
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A First-In-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GFB-024 as a Single Dose in Healthy Overweight and Obese Participants and as Multiple Doses in Participants With Type 2 Diabetes Mellitus

Conditions
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Kidney Diseases, Diabetic Nephropathies, Diabetes Complications, Diabetes Mellitus, Endocrine System Diseases

Intervention / Treatment
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* Drug: GFB-024
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years of age at the time of signing informed consent. Body mass index (BMI) between 25.0 and 40.0 kg/m2, inclusive, at Screening. Female participants will be of non-childbearing potential. Male participants will agree to use contraception while on study intervention and for at least 6 months after the last dose of study intervention. SAD cohorts only: Participants must be in good health. Repeat-dose cohort only: Type 2 diabetes mellitus (T2DM) treated with lifestyle modification or metformin, and in otherwise good health except for well-controlled common conditions associated with T2DM, such as hypertension and dyslipidemia. Exclusion Criteria: History of, or treatment for, psychiatric illness, including anxiety or depression within 5 years of the Screening visit. Participants with a history of attempted suicide or clinically significant suicidal ideation. History of cardiovascular disease. Blood pressure >155 mmHg systolic or >95 mmHg diastolic. History of alcoholism or drug/chemical abuse within 2 years prior to Screening. Alcohol consumption of >21 units per week for males and >14 units for females. One unit of alcohol equals 12 oz (360 mL) beer, 1.5 oz (45 mL) liquor, or 5 oz (150 mL) wine. History of significant hypersensitivity, intolerance, or allergy to more than one class of drugs. Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included. SAD cohorts only: Fasting glucose >126 mg/dL.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GFB-024 SAD Active<br>Single ascending dose arm of GFB-024 treatment | Drug: GFB-024<br>* Peripherally acting Cannabinoid-1 receptor inverse agonist monoclonal antibody<br>|
| Placebo Comparator: SAD Placebo<br>Single ascending dose arm of placebo treatment | Drug: Placebo<br>* Matched placebo<br>|
| Active Comparator: GFB-024 Repeat-dose Active<br>Repeat-dose arm of GFB-024 treatment | Drug: GFB-024<br>* Peripherally acting Cannabinoid-1 receptor inverse agonist monoclonal antibody<br>|
| Placebo Comparator: Repeat-dose Placebo<br>Repeat-dose arm of placebo treatment | Drug: Placebo<br>* Matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability following single ascending doses of GFB-024 | Number of participants with serious and other nonserious adverse events | Approximately 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability following repeated doses over 4 weeks of GFB-024 | Number of participants with serious and other nonserious adverse events | Approximately 13 weeks | 
| Characterize PK of GFB-024 following single ascending doses (Cmax) | Maximum serum concentration | Approximately 10 weeks | 
| Characterize PK of GFB-024 following single ascending doses (AUClast) | Area under the serum concentration-time curve from time zero to last measurable concentration | Approximately 10 weeks | 
| Characterize PK of GFB-024 following repeated doses (Cmax) | Maximum serum concentration | Approximately 13 weeks | 
| Characterize PK of GFB-024 following repeated doses (AUClast) | Area under the serum concentration-time curve from time zero to last measurable concentration | Approximately 13 weeks | 
| Characterize the incidence and persistence of immunogenicity of GFB-024 following single ascending doses | Number of participants with confirmed antidrug antibodies | Approximately 10 weeks | 
| Characterize the incidence and persistence of immunogenicity of GFB-024 following repeated doses | Number of participants with confirmed antidrug antibodies | Approximately 13 weeks |