First-in-Human Trial of Anti-ADAMTS-5 Nanobody in Healthy Volunteers

Study Overview
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Brief Summary
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This First-In-Human trial will be conducted in healthy male subjects to explore the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of single doses of M6495.

Official Title
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A Single-Center, Phase I, Randomized, Double Blind, Placebo-Controlled, First-In-Human Trial to Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of Subcutaneous Injected M6495 (Anti-ADAMTS-5 Nanobody) in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: M6495
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with Body Mass Index (BMI) of greater than or equal to (>=) 18.5 and less than or equal to (=<) 29.9 Kilogram per square meter (kg/m^2), and a body weight between 50 and 100 kg at screening. Subjects must agree to use effective method(s) of contraception during the trial. Other protocol defined inclusion criteria could apply. Exclusion Criteria: Subjects who have recently participated in other clinical trials. Donated blood, have a significant medical condition, history of drug hypersensitivity, consumption of large amounts of xanthine-containing foods or beverages, recent or ongoing concomitant medication, hypertension, tachycardia and significant findings on electrocardiogram Positive drug screening test, positive test for Hepatitis B or C or human immune deficiency virus (HIV), or have been kept in detention Other protocol defined exclusion criteria could apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M6495<br> | Drug: M6495<br>* Subjects will receive M6495 on Day 1<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subjects will receive placebo matched to M6495 on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) |  | Baseline up to Day 75 | 
| Occurrence of TEAEs and SAEs by Severity |  | Baseline up to Day 75 | 
| Number of Subjects With Injection Site Reactions (ISRs) |  | Baseline up to Day 75 | 
| Number of Subjects with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings |  | Baseline up to Day 75 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Area Under the Concentration-Time Curve From Time Zero to the Last Sampling Time (t) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Apparent Terminal Half-Life (t1/2) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Apparent Terminal Rate Constant (λz) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Apparent Body Clearance (CL/F) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Percent Change From Baseline in Serum Aggrecan Degradation neo-Epitope (ARGS) at Day 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 22, 29, 39, 49, 61 and 75 |  | Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 22, 29, 39, 49, 61 and 75 | 
| Number of Subjects With Anti-drug Antibodies (ADA) for M6495 |  | Pre-dose, Day 8, 22, 49 and 75 | 
| Levels of Anti-Drug Antibodies (ADA) Titers |  | Pre-dose, Day 8, 22, 49 and 75 | 
| Change From Baseline in Telemetry Electrocardiogram (ECG) Intervals Up to 24 hours post Day 1 dose |  | Baseline, Up to 24 hours post Day 1 dose | 
| Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates |  | Baseline up to Day 75 | 
| Maximal Effect (Imax) of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 
| Inhibitory Concentration (IC) 10, IC50 and IC90 of M6495 |  | Pre-dose and 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 504, 672, 912, 1152, 1440, 1776 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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M6495, anti-A disintegrin and metalloproteinase with thrombospondin motifs-5 nanobody, Osteoarthritis