Multiple Ascending Doses (MAD) of Anti-A Disintegrin and Metalloproteinase With Thrombospondin Motifs-5 (Anti-ADAMTS-5) Nanobody in Participants With Knee Osteoarthritis (OA)
Primary Purpose
Osteoarthritis, Knee
Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
M6495
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis
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
Sites / Locations
- DanTrials ApS
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
M6495
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)
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.
Occurrences of Injection Site Reactions
Secondary Outcome Measures
Maximum Observed Serum Concentration (Cmax) of M6495
Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495
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
Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays
Full Information
NCT ID
NCT03583346
First Posted
June 28, 2018
Last Updated
January 22, 2020
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT03583346
Brief Title
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
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
August 23, 2018 (Actual)
Primary Completion Date
July 31, 2019 (Actual)
Study Completion Date
July 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
M6495
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
M6495
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)
Time Frame
Day 1 up to Day 106
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings
Description
Number of participants with clinically significant change from baseline will be reported.
Time Frame
Day 1 up to Day 106
Title
Occurrences of Injection Site Reactions
Time Frame
Day 1 up to Day 43
Secondary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of M6495
Time Frame
Day 1 up to Day 106
Title
Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495
Time Frame
Day 1 up to Day 106
Title
Accumulation Ratio for Cmax (Racc [Cmax]) of M6495
Description
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
Time Frame
Day 1, 15 and 29
Title
Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays
Time Frame
Day 1 up to Day 106
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
DanTrials ApS
City
Copenhagen NV
ZIP/Postal Code
2400
Country
Denmark
12. IPD Sharing Statement
Learn more about this trial
Multiple Ascending Doses (MAD) of Anti-A Disintegrin and Metalloproteinase With Thrombospondin Motifs-5 (Anti-ADAMTS-5) Nanobody in Participants With Knee Osteoarthritis (OA)
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