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

Phase 1

Completed

• Conditions: Osteoarthritis, Knee
• Interventions: Drug: Placebo; Drug: M6495

• Registration Number: NCT03583346
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-28
• Study First Submitted QC: 2018-06-28
• Study First Posted: 2018-07-11
• Study Start: 2018-08-23
• Primary Completion: 2019-07-31
• Study Completion: 2019-07-31
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-22
• Last Update Posted: 2020-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
M6495	M6495	-

Primary Outcome Measures

Name	Time	Method
Occurrences of Injection Site Reactions	Day 1 up to Day 43
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.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays	Day 1 up to Day 106
Maximum Observed Serum Concentration (Cmax) 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
Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495	Day 1 up to Day 106

Trial Locations

Locations (1)

DanTrials ApS; 🇩🇰 Copenhagen NV, Denmark