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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03224702
Recruitment Status : Completed
First Posted : July 21, 2017
Last Update Posted : May 2, 2019
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: M6495 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 4, 2017
Actual Primary Completion Date : August 6, 2018
Actual Study Completion Date : August 6, 2018

Arm Intervention/treatment
Experimental: M6495 Drug: M6495
Subjects will receive M6495 on Day 1

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




Primary Outcome Measures :
  1. Occurrence of Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) [ Time Frame: Baseline up to Day 75 ]
  2. Occurrence of TEAEs and SAEs by Severity [ Time Frame: Baseline up to Day 75 ]
  3. Number of Subjects With Injection Site Reactions (ISRs) [ Time Frame: Baseline up to Day 75 ]
  4. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Apparent Terminal Rate Constant (λz) 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. Number of Subjects With Anti-drug Antibodies (ADA) for M6495 [ Time Frame: Pre-dose, Day 8, 22, 49 and 75 ]
  11. Levels of Anti-Drug Antibodies (ADA) Titers [ Time Frame: Pre-dose, Day 8, 22, 49 and 75 ]
  12. 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 ]
  13. Slope of Exposure vs QTc From Digital Electrocardiogram Triplicates [ Time Frame: Baseline up to Day 75 ]
  14. 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 ]
  15. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03224702


Locations
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Denmark
DanTrials ApS c/o Bispebjerg Hospital
Copenhagen, Denmark, DK-2400
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT03224702    
Other Study ID Numbers: MS200572-0009
2017-001663-21 ( EudraCT Number )
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: May 2, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck KGaA, Darmstadt, Germany:
M6495
anti-A disintegrin and metalloproteinase with thrombospondin motifs-5 nanobody
Osteoarthritis