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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 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. Identifier: NCT03583346
Recruitment Status : Completed
First Posted : July 11, 2018
Last Update Posted : January 23, 2020
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Drug: M6495 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : August 23, 2018
Actual Primary Completion Date : July 31, 2019
Actual Study Completion Date : July 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: M6495 Drug: M6495
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 Comparator: Placebo Drug: Placebo
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 Outcome Measures :
  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 Outcome Measures :
  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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT03583346

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DanTrials ApS
Copenhagen NV, Denmark, 2400
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
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Responsible Party: Merck KGaA, Darmstadt, Germany Identifier: NCT03583346    
Other Study ID Numbers: MS200572_0003
2018-000797-29 ( EudraCT Number )
First Posted: July 11, 2018    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: January 2020

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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:
Anti-ADAMTS-5 Nanobody
Additional relevant MeSH terms:
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Osteoarthritis, Knee
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases