Osteoarthritis, Knee
Conditions
Keywords
M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis
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.
Interventions
DRUGM6495
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.
DRUGPlacebo
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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs) | Day 1 up to Day 106 | — |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings | Day 1 up to Day 106 | Number of participants with clinically significant change from baseline will be reported. |
| Occurrences of Injection Site Reactions | Day 1 up to Day 43 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of M6495 | Day 1 up to Day 106 | — |
| Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays | Day 1 up to Day 106 | — |
| Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495 | Day 1 up to Day 106 | — |
| Accumulation Ratio for Cmax (Racc [Cmax]) of M6495 | 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 |
Countries
Denmark
Outcome results
None listed