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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03224702
• Date of registration: 19/07/2017
• Prospective Registration: Yes
• Primary sponsor: Merck KGaA, Darmstadt, Germany
• Public title: First-in-Human Trial of Anti-ADAMTS-5 Nanobody in Healthy Volunteers
• Scientific 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
• Date of first enrolment: September 4, 2017
• Target sample size: 54
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03224702
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Denmark, Germany

Contacts

• Name: Medical Responsible
• Affiliation: Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Healthy

Intervention(s)

Drug: Placebo

Drug: M6495

Primary Outcome(s)

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]

Number of Subjects With Injection Site Reactions (ISRs) [Time Frame: Baseline up to Day 75]

Occurrence of TEAEs and SAEs by Severity [Time Frame: Baseline up to Day 75]

Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) [Time Frame: Baseline up to Day 75]

Secondary Outcome(s)

Apparent Body Clearance (CL/F) of M6495 [Time Frame: 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 [Time Frame: 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]

Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates [Time Frame: Baseline up to Day 75]

Time to Reach Maximum Observed Serum Concentration (Tmax) of M6495 [Time Frame: 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 (?z) of M6495 [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 22, 29, 39, 49, 61 and 75]

Inhibitory Concentration (IC) 10, IC50 and IC90 of M6495 [Time Frame: 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 [Time Frame: 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 [Time Frame: Pre-dose, Day 8, 22, 49 and 75]

Maximal Effect (Imax) of M6495 [Time Frame: 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 [Time Frame: Baseline, Up to 24 hours post Day 1 dose]

Number of Subjects With Anti-drug Antibodies (ADA) for M6495 [Time Frame: Pre-dose, Day 8, 22, 49 and 75]

Secondary ID(s)

2017-001663-21

MS200572-0009

Source(s) of Monetary Support

Please refer to primary and secondary sponsors