Clinical trial NCT03224702: First-in-Human Trial of Anti-ADAMTS-5 Nanobody in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: M6495
anti-A disintegrin and metalloproteinase with thrombospondin motifs-5 nanobody
Osteoarthritis
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2017-07-21
Enrollment: 54
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs)
timeFrame: Baseline up to Day 75
measure: Occurrence of TEAEs and SAEs by Severity
timeFrame: Baseline up to Day 75
measure: Number of Subjects With Injection Site Reactions (ISRs)
timeFrame: Baseline up to Day 75
measure: Number of Subjects with Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Baseline up to Day 75
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of M6495
timeFrame: 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
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of M6495
timeFrame: 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
measure: 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
timeFrame: 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
measure: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M6495
timeFrame: 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
measure: Apparent Terminal Half-Life (t1/2) of M6495
timeFrame: 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
measure: Apparent Terminal Rate Constant (λz) of M6495
timeFrame: 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
measure: Apparent Body Clearance (CL/F) of M6495
timeFrame: 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
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of M6495
timeFrame: 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
measure: 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
timeFrame: Baseline, Day 1, 2, 3, 4, 5, 6, 7, 8, 11, 15, 22, 29, 39, 49, 61 and 75
measure: Number of Subjects With Anti-drug Antibodies (ADA) for M6495
timeFrame: Pre-dose, Day 8, 22, 49 and 75
measure: Levels of Anti-Drug Antibodies (ADA) Titers
timeFrame: Pre-dose, Day 8, 22, 49 and 75
measure: Change From Baseline in Telemetry Electrocardiogram (ECG) Intervals Up to 24 hours post Day 1 dose
timeFrame: Baseline, Up to 24 hours post Day 1 dose
measure: Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates
timeFrame: Baseline up to Day 75
measure: Maximal Effect (Imax) of M6495
timeFrame: 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
measure: Inhibitory Concentration (IC) 10, IC50 and IC90 of M6495
timeFrame: 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
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: DanTrials ApS c/o Bispebjerg Hospital
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: