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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: M6495; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2400
    • DanTrials ApS c/o Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Subjects will receive placebo matched to M6495 on Day 1
Experimental: M6495	Drug: M6495; Subjects will receive M6495 on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2017
• Primary Completion (Actual): August 6, 2018
• Study Completion (Actual): August 6, 2018

Study Registration Dates

• First Submitted: July 19, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Osteoarthritis; M6495; anti-A disintegrin and metalloproteinase with thrombospondin motifs-5 nanobody
• Other Study ID Numbers: MS200572-0009; 2017-001663-21 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No