Osteoarthritis, KneePhase 1NCT03583346
Multiple Ascending Doses (MAD) of Anti-A Disintegrin and Metalloproteinase With Thrombospondin Motifs-5 (Anti-ADAMTS-5) Nanobody in Participants With Knee Osteoarthritis (OA)
A Phase 1 study testing M6495 in people with Osteoarthritis, Knee, run by Merck KGaA, Darmstadt, Germany at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- M6495
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteDenmark
- Study dates
- 23 Aug 2018to 31 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- M6495, Placebo
- Keywords
- M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M6495Drug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| M6495 | Experimental | Not described Receives: Drug: M6495 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs)
Measured: 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.
Measured: Day 1 up to Day 106
Occurrences of Injection Site Reactions
Measured: Day 1 up to Day 43
Secondary outcomes (4)
Maximum Observed Serum Concentration (Cmax) of M6495
Measured: Day 1 up to Day 106
Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495
Measured: Day 1 up to Day 106
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
Measured: Day 1, 15 and 29
Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays
Measured: Day 1 up to Day 106
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start23 Aug 2018
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03583346
- Sponsor's protocol ID
- MS200572_0003
- Other IDs
- 2018-000797-29, 2018
- Status last verified
- Jan 2020
- First submitted
- 28 Jun 2018
- Last updated
- 23 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03583346
- Acronym / sponsor ID
- MS200572_0003
- Conditions
- Osteoarthritis, Knee
- Keywords
- M6495, Anti-ADAMTS-5 Nanobody, Osteoarthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 23 Aug 2018 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| M6495 | Experimental | Drug: M6495 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M6495Participants 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. | Drug | M6495 |
| PlaceboParticipants 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. | Drug | Placebo |
Primary outcome
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.
Occurrences of Injection Site Reactions
Time frame: Day 1 up to Day 43
4 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of M6495
Time frame: Day 1 up to Day 106
Dose Normalized Maximum Serum Concentration (Cmax/Dose) of M6495
Time frame: Day 1 up to Day 106
Accumulation Ratio for Cmax (Racc [Cmax]) of M6495
Time frame: Day 1, 15 and 29
Immunogenicity of M6495 as Assessed by Antidrug Antibodies (ADA) Assays
Time frame: Day 1 up to Day 106
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing M6495 in people with Osteoarthritis, Knee, run by Merck KGaA, Darmstadt, Germany at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrences of Treatment-emergent Adverse Events (TEAEs), Treatment-related AEs and Serious AEs (SAEs) (time frame: Day 1 up to Day 106). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2020.