Clinical trial 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoarthritis, Knee
Keywords: M6495
Anti-ADAMTS-5 Nanobody
Osteoarthritis
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-07-11
Enrollment: 32
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)
timeFrame: Day 1 up to Day 106
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
timeFrame: Day 1 up to Day 106
measure: Occurrences of Injection Site Reactions
timeFrame: Day 1 up to Day 43
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of M6495
timeFrame: Day 1 up to Day 106
measure: Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495
timeFrame: Day 1 up to Day 106
measure: Accumulation Ratio for Cmax (Racc [Cmax]) of M6495
timeFrame: Day 1, 15 and 29
measure: Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays
timeFrame: Day 1 up to Day 106
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: DanTrials ApS
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: