A Single and Multiple Ascending Dose Study of Subcutaneously Administered JNJ-75220795

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and tolerability of single and multiple subcutaneous (SC) doses of JNJ-75220795.

Official Title
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A Double-Blind, Placebo-Controlled, Randomized, Multipart, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered JNJ-75220795

Conditions
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Fatty Liver Disease

Intervention / Treatment
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* Drug: JNJ-75220795
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with certain genetic predisposition to non-alcoholic fatty liver disease (NAFLD) determined at screening Presence of liver steatosis at screening Participants on anti-hypertensive and/or lipid lowering medications and/or glucose lowering medications must be on stable dose(s) for at least 4 weeks prior to screening Weight stable defined as no more than 5% body weight loss or gain within 3 months prior to screening and no more than 5% body weight loss or gain from screening to randomization Exclusion Criteria: Known allergies, hypersensitivity, or intolerance to JNJ-75220795 or its excipients History of hepatitis B surface antigen (HbsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HbsAg or anti-HCV at screening History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: Single Ascending Dose (SAD)<br>Participants in cohorts 1-5 and cohorts 3a-5a will receive subcutaneous (SC) injection of single dose (Part A) of JNJ-75220795 or matching placebo. | Drug: JNJ-75220795<br>* JNJ-75220795 will be administered subcutaneously.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously.<br>|
| Experimental: Multiple Ascending Dose (MAD)<br>Participants in cohorts 6-8 will receive SC injection of 2 doses (Part B) of JNJ-75220795 or matching placebo. Participants in cohorts 9-11 will receive SC injection of 4 doses (Part C) of JNJ-75220795 or matching placebo. | Drug: JNJ-75220795<br>* JNJ-75220795 will be administered subcutaneously.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Signs and Symptoms/ Adverse Events (AEs) | Number of participants with treatment-emergent signs and symptoms/adverse events (including allergic reactions/hypersensitivity and local injection site reactions) will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Treatment-emergent adverse events (TEAEs) are defined as AEs with onset or worsening on or after date of first dose of study treatment. | Up to Day 182 | 
| Number of Participants With Change From Baseline in Vital Signs Abnormalities | Number of participants with change from baseline in vital signs abnormalities including temperature, heart rate, respiratory rate, and blood pressure (supine) will be reported. | Baseline, up to Day 168 | 
| Number of Participants With Change From Baseline in Clinical Laboratory Abnormalities | Number of participants with change from baseline in clinical laboratory abnormalities including hematology, chemistry and urinalysis will be reported. | Baseline, up to Day 168 | 
| Number of Participants With Change From Baseline in Physical Examination Abnormalities | Number of participants with change from baseline in physical examination abnormalities will be reported. | Baseline, up to Day 168 | 
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) Abnormalities | Number of participants with change from baseline in ECG abnormalities will be reported. | Baseline, up to Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Liver Fat Content | Percent change from baseline in liver fat content will be reported. | Baseline, weeks 6, 12, 18 and 24 | 
| Plasma Concentration of JNJ-75220795 Over Time | Plasma samples will be analyzed to determine concentrations of JNJ-75220795. | SAD: Predose, up to Day 3 and MAD: Predose, up to Day 86 | 
| Percentage of Participants With Treatment-emergent Anti Drug Antibodies (ADA) | Percentage of participants with treatment-emergent ADA will be assessed using a validated assay for ADA analysis. | Up to Day 168 |