Osteoarthritis
Conditions
Keywords
Knee,, osteoarthritis, pain assessment
Brief summary
A double-blind, randomized, placebo-controlled, parallel-group, multi-site, clinical trial to confirm the efficacy and safety of repeated injections of RTX-GRT7039 versus placebo in patients who have pain associated with osteoarthritis of the knee despite standard of care.
Detailed description
This trial comprises a total observation period of up to 52 weeks.
Interventions
DRUGRTX-GRT7039
RTX-GRT7039 intra-articular injection.
DRUGPlacebo
Placebo matching RTX-GRT7039 intra-articular injection.
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has given written informed consent to participate. * The participant is 18 years of age or older at the Screening Visit. * The participant has a diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I to III. * There is a documented history indicating that participant has insufficient pain relief with previous Standard of Care.
Exclusion criteria
* The participant has past joint replacement surgery of the index knee. * The participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening. * The participant has periarticular pain from any cause other than osteoarthritis, including referred pain, bursitis, or tendonitis. * The participant has clinical hip osteoarthritis on the side of the index knee. * The participant has pre-existing osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, severe bone on bone osteoarthritis, knee pain attributable to disease other than osteoarthritis, or the participant has rapidly progressing osteoarthritis (RPOA) Type I or Type II. * The participant has significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus \>10, valgus \>10) by X-ray as assessed by independent Central Readers at Screening Visit. * The participant has other conditions that could affect trial endpoint assessments of the index knee. * The participant has current clinically significant disease(s) or condition(s) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the participant's participation for the full duration of the trial. * The participant has a history of hypersensitivity to resiniferatoxin (RTX) or any similar component (capsaicin, chili peppers). * The participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit. * The participant is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site or is a family member of the employees or the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean (Standard Error) [LS-mean (SE)] Change From Baseline in WOMAC Pain Subscale Score at Week 12 | Baseline up to Week 12 | Difference in mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score at Week 12 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 26 | From Baseline up to Week 26 | Difference in mean change from baseline in WOMAC pain subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
| LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 52 | From Baseline up to Week 52 | Difference in mean change from baseline in WOMAC pain subscale score at Week 52 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
| LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 12 | From Baseline up to Week 12 | Difference in mean change from baseline in WOMAC physical function subscale score at Week 12 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
| LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 26 | From Baseline up to Week 26 | Difference in mean change from baseline in WOMAC physical function subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
| LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 52 | From Baseline up to Week 52 | Difference in mean change from baseline in WOMAC physical function subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine). The scores are averaged over the number of questions. |
Countries
Canada, Czechia, France, Germany, Italy, Japan, Mexico, Netherlands, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RTX-GRT7039 Participants received intra-articular injections of RTX-GRT7039 (2 injections: Day 1 and Week 26) during the 52-week double-blind treatment period. | 234 |
| Placebo Participants received intra-articular injections of placebo matching to RTX-GRT7039 (2 injections: Day 1 and Week 26) during the 52-week double-blind treatment period. | 232 |
| Total | 466 |
Baseline characteristics
| Characteristic | RTX-GRT7039 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 8.4 | 67.1 years STANDARD_DEVIATION 8.32 | 66.8 years STANDARD_DEVIATION 8.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 17 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 214 Participants | 214 Participants | 428 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Female | 163 Participants | 174 Participants | 337 Participants |
| Sex: Female, Male Male | 71 Participants | 58 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 234 | 0 / 232 |
| other Total, other adverse events | 53 / 234 | 40 / 232 |
| serious Total, serious adverse events | 17 / 234 | 14 / 232 |
Outcome results
Primary
Least Squares Mean (Standard Error) [LS-mean (SE)] Change From Baseline in WOMAC Pain Subscale Score at Week 12
Difference in mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score at Week 12 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: Baseline up to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | Least Squares Mean (Standard Error) [LS-mean (SE)] Change From Baseline in WOMAC Pain Subscale Score at Week 12 | -2.959 score on a scale | Standard Error 0.15 |
| Placebo | Least Squares Mean (Standard Error) [LS-mean (SE)] Change From Baseline in WOMAC Pain Subscale Score at Week 12 | -2.847 score on a scale | Standard Error 0.15 |
Secondary
LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 26
Difference in mean change from baseline in WOMAC pain subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: From Baseline up to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 26 | -2.564 score on a scale | Standard Error 0.15 |
| Placebo | LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 26 | -2.597 score on a scale | Standard Error 0.16 |
Secondary
LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 52
Difference in mean change from baseline in WOMAC pain subscale score at Week 52 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: From Baseline up to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 52 | -2.686 score on a scale | Standard Error 0.18 |
| Placebo | LS-mean (SE) Change From Baseline in WOMAC Pain Subscale Score at Week 52 | -2.823 score on a scale | Standard Error 0.18 |
Secondary
LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 12
Difference in mean change from baseline in WOMAC physical function subscale score at Week 12 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: From Baseline up to Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 12 | -2.802 score on a scale | Standard Error 0.14 |
| Placebo | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 12 | -2.740 score on a scale | Standard Error 0.14 |
Secondary
LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 26
Difference in mean change from baseline in WOMAC physical function subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: From Baseline up to Week 26
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 26 | -2.503 score on a scale | Standard Error 0.14 |
| Placebo | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 26 | -2.552 score on a scale | Standard Error 0.15 |
Secondary
LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 52
Difference in mean change from baseline in WOMAC physical function subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo. The WOMAC pain subscale consists of 5 questions using an 11-point numeric rating scale (NRS, from 0 = no pain to 10 = pain as bad as you can imagine).
Time frame: From Baseline up to Week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| RTX-GRT7039 | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 52 | -2.664 score on a scale | Standard Error 0.16 |
| Placebo | LS-mean (SE) Change From Baseline in WOMAC Physical Function Subscale Score at Week 52 | -2.728 score on a scale | Standard Error 0.16 |