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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

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03224702
Enrollment
54
Registered
2017-07-21
Start date
2017-09-04
Completion date
2018-08-06
Last updated
2019-05-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

M6495, anti-A disintegrin and metalloproteinase with thrombospondin motifs-5 nanobody, Osteoarthritis

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.

Interventions

DRUGM6495

Subjects will receive M6495 on Day 1

DRUGPlacebo

Subjects will receive placebo matched to M6495 on Day 1

Sponsors

Merck KGaA, Darmstadt, Germany
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frame
Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)Baseline up to Day 75
Occurrence of TEAEs and SAEs by SeverityBaseline 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) FindingsBaseline up to Day 75

Secondary

MeasureTime frame
Time to Reach Maximum Observed Serum Concentration (Tmax) of M6495Pre-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 TriplicatesBaseline up to Day 75
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 M6495Pre-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 M6495Pre-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 M6495Pre-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
Number of Subjects With Anti-drug Antibodies (ADA) for M6495Pre-dose, Day 8, 22, 49 and 75
Apparent Body Clearance (CL/F) of M6495Pre-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 M6495Pre-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 75Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 22, 29, 39, 49, 61 and 75
Maximal Effect (Imax) of M6495Pre-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 M6495Pre-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 M6495Pre-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) TitersPre-dose, Day 8, 22, 49 and 75
Change From Baseline in Telemetry Electrocardiogram (ECG) Intervals Up to 24 hours post Day 1 doseBaseline, Up to 24 hours post Day 1 dose
Maximum Observed Serum Concentration (Cmax) of M6495Pre-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

Countries

Denmark

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026