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

Merck KGaA, Darmstadt, Germany1 site in 1 country54 target enrollmentSeptember 4, 2017

ConditionsHealthy

InterventionsM6495 Placebo

DrugsM6495 Placebo

Overview

Phase: Phase 1
Intervention: M6495
Conditions: Healthy
Sponsor: Merck KGaA, Darmstadt, Germany
Enrollment: 54
Locations: 1
Primary Endpoint: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

September 4, 2017

End Date

August 6, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Merck KGaA, Darmstadt, Germany

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

M6495

Intervention: M6495

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

Time Frame: Baseline up to Day 75

Number of Subjects With Injection Site Reactions (ISRs)

Time Frame: 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

Time Frame: Baseline up to Day 75

Occurrence of TEAEs and SAEs by Severity

Time Frame: Baseline up to Day 75

Secondary Outcomes

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)
Levels of Anti-Drug Antibodies (ADA) Titers(Pre-dose, Day 8, 22, 49 and 75)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates(Baseline up to Day 75)
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)