Skip to main content
OpenTrials
Completed

NCT Number: NCT03583346

Multiple Ascending Doses (MAD) of Anti-A Disintegrin and Metalloproteinase With Thrombospondin Motifs-5 (Anti-ADAMTS-5) Nanobody in Participants With Knee Osteoarthritis (OA)

The study will be conducted in participants with symptomatic knee OA to explore the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of MAD of M6495.

Completed

Looking for future studies?

Notify Me

Key information

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

DanTrials ApS

Copenhagen NV, 2400, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Kellgren Lawrence (KL) radiological Grade of 2 to 4 in the target knee
  • Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore of greater than or equal to (>=) 40 out of 100 in the target knee at screening
  • Primary or post-traumatic femorotibial OA according to American College of Rheumatology clinical and radiographic criteria
  • Have completed at least 4 days of the participant 7-day diary in the period from Day -8 to Day 1
  • Can give signed informed consent
  • Other protocol defined inclusion criteria could apply

Exclusion criteria

  • History of arthroscopy or intra-articular administration of corticosteroids or hyaluronic acid into the target knee within 6 months before screening
  • Intention of having major knee surgeries or total knee replacement during the time frame of this study in either knee
  • Secondary OA in target knee joint because of joint dysplasia, aseptic osteonecrosis, acromegaly, Paget disease, Stickler syndrome, hemochromatosis, gout, chondrocalcinosis, or calcium pyrophosphate deposition disease
  • Any known active systemic infection, including infection that might compromise the immune system such as human immunodeficiency virus, or hepatitis B or C
  • History of myocardial infarction or cerebrovascular event within 6 months prior to screening, or current active angina pectoris, symptomatic heart failure, seizures, untreated hypertension, gastrointestinal bleeding, or any other significant medical condition in the Investigator's opinion
  • History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix, unless considered cured >= 5 years
  • Other protocol defined exclusion criteria could apply

Treatment and study plan

M6495

Drug

Participants will receive escalated dose of M6495 bi-weekly on Day 1, 15 and 29 in cohort 1 to 3 and weekly on Day 1, 8, 15, 22, 29 and 36 in cohort 4.

Placebo

Drug

Participants will receive placebo matched to M6495 bi-weekly on Day 1, 15 and 29 in cohort 1 to 3 and weekly on Day 1, 8, 15, 22, 29 and 36 in cohort 4.

Primary outcomes

  1. Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)

    Time frame: Day 1 up to Day 106

  2. Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings

    Time frame: Day 1 up to Day 106

    Number of participants with clinically significant change from baseline will be reported.

  3. Occurrences of Injection Site Reactions

    Time frame: Day 1 up to Day 43

Secondary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of M6495

    Time frame: Day 1 up to Day 106

  2. Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495

    Time frame: Day 1 up to Day 106

  3. Accumulation Ratio for Cmax (Racc [Cmax]) of M6495

    Time frame: Day 1, 15 and 29

    Following Racc parameters will be measured:

    • Racc15 (Cmax): Cmax at Day 15/Cmax at Day 1
    • Racc29 (Cmax): Cmax at Day 29/Cmax at Day 1
  4. Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays

    Time frame: Day 1 up to Day 106

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

A Phase Ib, Single-center, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multiple Ascending Dose Study to Assess Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Injections of M6495 (Anti-ADAMTS-5 Nanobody) in Participants With Symptomatic Knee Osteoarthritis

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jul 11, 2018
Registry last updated
Jan 23, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.