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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: M6495; Drug: Placebo

• Registration Number: NCT03224702
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-19
• Study First Submitted QC: 2017-07-19
• Study First Posted: 2017-07-21
• Study Start: 2017-09-04
• Primary Completion: 2018-08-06
• Study Completion: 2018-08-06
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-30
• Last Update Posted: 2019-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 54

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
M6495	M6495	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)	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
Occurrence of TEAEs and SAEs by Severity	Baseline up to Day 75

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

DanTrials ApS c/o Bispebjerg Hospital; 🇩🇰 Copenhagen, Denmark