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

Merck KGaA, Darmstadt, Germany1 site in 1 country32 target enrollmentAugust 23, 2018

ConditionsOsteoarthritis, Knee

InterventionsM6495 Placebo

DrugsM6495 Placebo

Overview

Phase: Phase 1
Intervention: M6495
Conditions: Osteoarthritis, Knee
Sponsor: Merck KGaA, Darmstadt, Germany
Enrollment: 32
Locations: 1
Primary Endpoint: Occurrences of Injection Site Reactions
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 23, 2018

End Date

July 31, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Merck KGaA, Darmstadt, Germany

Responsible Party

Sponsor

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

Arms & Interventions

M6495

Intervention: M6495

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Occurrences of Injection Site Reactions

Time Frame: Day 1 up to Day 43

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

Time Frame: 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

Time Frame: Day 1 up to Day 106

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

Secondary Outcomes

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)
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)