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

NCT03583346 | Completed Phase 1 DMC

• 2 other identifiers: MS200572_00032018-000797-29
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoarthritis, Knee

Keywords

M6495; Anti-ADAMTS-5 Nanobody; Osteoarthritis

Outcome Measures

Primary Outcomes (3)

• 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

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

  Day 1 up to Day 106

• Occurrences of Injection Site Reactions

  Day 1 up to Day 43

Secondary Outcomes (4)

• Maximum Observed Serum Concentration (Cmax) of M6495

  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

• Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays

  Day 1 up to Day 106

Study Arms (2)

M6495

EXPERIMENTAL

Drug: M6495

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

M6495 DRUG

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.

M6495

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

DanTrials ApS

Copenhagen NV, 2400, Denmark

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2018
• First Posted: July 11, 2018
• Study Start: August 23, 2018
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: January 23, 2020

Record last verified: 2020-01

Locations

DK (1)