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

Osteoarthritis, Knee Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03583346
• Other study ID #: MS200572_0003
• Secondary ID: 2018-000797-29
• Status: Completed
• Phase: Phase 1
• Start date: August 23, 2018
• Est. completion date: July 31, 2019

Study information

• Verified date: January 2020
• Source: Merck KGaA, Darmstadt, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• M6495
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.
• Placebo
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.

Locations

Country	Name	City	State
Denmark	DanTrials ApS	Copenhagen NV

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)		Day 1 up to Day 106
Primary	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
Primary	Occurrences of Injection Site Reactions		Day 1 up to Day 43
Secondary	Maximum Observed Serum Concentration (Cmax) of M6495		Day 1 up to Day 106
Secondary	Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495		Day 1 up to Day 106
Secondary	Accumulation Ratio for Cmax (Racc [Cmax]) of M6495	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	Day 1, 15 and 29
Secondary	Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays		Day 1 up to Day 106