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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

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Studies a U.S. FDA-regulated Device Product

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

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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