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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03224702
• Other study ID #: MS200572-0009
• Secondary ID: 2017-001663-21
• Status: Completed
• Phase: Phase 1
• Start date: September 4, 2017
• Est. completion date: August 6, 2018

Study information

• Verified date: April 2019
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: August 6, 2018
• Est. primary completion date: August 6, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• M6495
Subjects will receive M6495 on Day 1
• Placebo
Subjects will receive placebo matched to M6495 on Day 1

Locations

Country	Name	City	State
Denmark	DanTrials ApS c/o Bispebjerg Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)		Baseline up to Day 75
Primary	Occurrence of TEAEs and SAEs by Severity		Baseline up to Day 75
Primary	Number of Subjects With Injection Site Reactions (ISRs)		Baseline up to Day 75
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apparent Terminal Rate Constant (?z) 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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Subjects With Anti-drug Antibodies (ADA) for M6495		Pre-dose, Day 8, 22, 49 and 75
Secondary	Levels of Anti-Drug Antibodies (ADA) Titers		Pre-dose, Day 8, 22, 49 and 75
Secondary	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
Secondary	Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates		Baseline up to Day 75
Secondary	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
Secondary	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