Osteoarthritis of Knee
Conditions
Brief summary
This is a phase IIb, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of MM-II in subjects with symptomatic knee OA as compared to matching placebo.
Interventions
DRUGMM-II dose I
Intra-articular injection
DRUGMM-II dose II
Intra-articular injection
DRUGMM-II dose III
Intra-articular injection
DRUGPlacebo
Intra-articular injection
Sponsors
Moebius Medical Ltd.
Nordic Bioscience Clinical Development (NBCD)
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is able to provide written consent, understand study requirements, is prepared to complete study procedures and is able to independently communicate meaningfully with study personnel 2. Presence of index knee pain for at least 6 months prior to Screening 3. Men or women ≥ 40 years of age at the time of Screening 4. Radiographic evidence of knee Osteoarthritis
Exclusion criteria
1. Pain in the contralateral knee with a severity of ≥ 30 mm on a 100 mm VAS 2. Presence of ≥ 40 mm on a 100 mm VAS pain in any other joints 3. Concomitant moderate or large size synovial fluid effusion of the index knee at Screening . 4. Known diagnosis of infection in the index knee in the past five years prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | Week 12 | The pain score is based on a score of 0 to 4; the higher the score, the higher the amount of pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | Week 26 | Knee pain will be assessed on a score of 0 to 100; the lower on the scale, the less the amount of knee pain experienced. Weekly post-baseline average daily knee pain scores will be calculated. |
| Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | Week 26 | Global pain will be assessed on a score of 0 to 100; the lower on the scale, the less the amount of global pain experienced. Weekly post-baseline average daily global pain scores will be calculated |
Countries
Denmark, Hong Kong, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: MM-II 1 ml MM-II 1 ml
MM-II dose I: Intra-articular injection | 103 |
| Arm B: MM-II 3 ml MM-II 3 ml
MM-II dose II: Intra-articular injection | 83 |
| Arm C: MM-II 6 ml MM-II 6 ml
MM-II dose III: Intra-articular injection | 76 |
| Arm 4: Placebo 1ml Placebo 1ml
Placebo: Intra-articular injection | 28 |
| Arm 5: Placebo 3ml Placebo 3ml
Placebo: Intra-articular injection | 79 |
| Arm 6: Placebo 6ml Placebo 6ml
Placebo: Intra-articular injection | 28 |
| Total | 397 |
Baseline characteristics
| Characteristic | Arm A: MM-II 1 ml | Arm B: MM-II 3 ml | Arm C: MM-II 6 ml | Arm 4: Placebo 1ml | Arm 5: Placebo 3ml | Arm 6: Placebo 6ml | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized ≤ 65 Years | 65 participants | 41 participants | 52 participants | 19 participants | 50 participants | 15 participants | 242 participants |
| Age, Customized > 65 Years | 38 participants | 42 participants | 24 participants | 9 participants | 29 participants | 13 participants | 155 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 13 Participants | 16 Participants | 3 Participants | 8 Participants | 5 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 70 Participants | 60 Participants | 25 Participants | 71 Participants | 23 Participants | 338 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Denmark | 47 participants | 27 participants | 27 participants | 13 participants | 31 participants | 9 participants | 154 participants |
| Region of Enrollment Hong Kong | 29 participants | 19 participants | 17 participants | 5 participants | 21 participants | 5 participants | 96 participants |
| Region of Enrollment United States | 27 participants | 37 participants | 32 participants | 10 participants | 27 participants | 14 participants | 147 participants |
| Sex: Female, Male Female | 71 Participants | 58 Participants | 39 Participants | 20 Participants | 51 Participants | 19 Participants | 258 Participants |
| Sex: Female, Male Male | 32 Participants | 25 Participants | 37 Participants | 8 Participants | 28 Participants | 9 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 86 | 0 / 74 | 0 / 28 | 0 / 78 | 0 / 28 |
| other Total, other adverse events | 75 / 102 | 49 / 86 | 49 / 74 | 15 / 28 | 46 / 78 | 19 / 28 |
| serious Total, serious adverse events | 4 / 102 | 0 / 86 | 3 / 74 | 0 / 28 | 3 / 78 | 1 / 28 |
Outcome results
Primary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score
The pain score is based on a score of 0 to 4; the higher the score, the higher the amount of pain.
Time frame: Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: MM-II 1 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -1.28 score on a scale | Standard Error 0.079 |
| Arm B: MM-II 3 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -1.35 score on a scale | Standard Error 0.086 |
| Arm C: MM-II 6 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -1.14 score on a scale | Standard Error 0.092 |
| Arm 4: Placebo 1 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -0.96 score on a scale | Standard Error 0.143 |
| Arm 5: Placebo 3 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -1.11 score on a scale | Standard Error 0.089 |
| Arm 6: Placebo 6 ml | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Score | -1.10 score on a scale | Standard Error 0.142 |
p-value: 0.85Mixed Models Analysis
p-value: 0.085Mixed Models Analysis
p-value: 0.85Mixed Models Analysis
Secondary
Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS
Global pain will be assessed on a score of 0 to 100; the lower on the scale, the less the amount of global pain experienced. Weekly post-baseline average daily global pain scores will be calculated
Time frame: Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: MM-II 1 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -21.0 score on a scale | Standard Error 3.12 |
| Arm B: MM-II 3 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -22.1 score on a scale | Standard Error 3.54 |
| Arm C: MM-II 6 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -14.4 score on a scale | Standard Error 3.69 |
| Arm 4: Placebo 1 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -17.6 score on a scale | Standard Error 5.86 |
| Arm 5: Placebo 3 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -12.2 score on a scale | Standard Error 3.55 |
| Arm 6: Placebo 6 ml | Change From Baseline in Weekly Average of Daily Global Pain Scores by VAS | -26.3 score on a scale | Standard Error 6.15 |
p-value: 0.042Mixed Models Analysis
p-value: 0.037Mixed Models Analysis
p-value: 0.648Mixed Models Analysis
Secondary
Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS
Knee pain will be assessed on a score of 0 to 100; the lower on the scale, the less the amount of knee pain experienced. Weekly post-baseline average daily knee pain scores will be calculated.
Time frame: Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Arm A: MM-II 1 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -30.4 score on a scale | Standard Error 2.81 |
| Arm B: MM-II 3 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -34.5 score on a scale | Standard Error 3.08 |
| Arm C: MM-II 6 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -23.1 score on a scale | Standard Error 3.26 |
| Arm 4: Placebo 1 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -28.2 score on a scale | Standard Error 5.19 |
| Arm 5: Placebo 3 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -22.7 score on a scale | Standard Error 3.2 |
| Arm 6: Placebo 6 ml | Change From Baseline in Weekly Average of Daily Knee Pain Scores by VAS | -30.0 score on a scale | Standard Error 5.15 |
p-value: 0.062Mixed Models Analysis
p-value: 0.007Mixed Models Analysis
p-value: 0.936Mixed Models Analysis