Obesity
Conditions
Brief summary
This study will look at participants body weight from the start to the end of the study. It will also look at how much pain participants have in participants knee from the start to the end of the study and how this affects participants daily life. This is to compare the effect on body weight and pain in the knee in people taking semaglutide with people taking dummy medicine. Participants will either get semaglutide or dummy medicine. Which treatment participants get is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. During the study, participants will have talks with study staff about how to eat healthy food and how to be more physically active. The study will last for about 1 ½ years. Participants will have 14 clinic visits with the study staff. At the first clinic visit participants will have a blood sample taken. Participants will have an X-ray of participants knee taken at the first visit. If participants have had an X-ray recently, this may not be needed. At 6 of the clinic visits participants cannot take pain medications for 3 days before the visit. Participants cannot take part if participants have had a joint replacement surgery in participants knee. Participants cannot take part if participants have or have had diabetes. Women: Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.
Interventions
semaglutide subcutaneous (s.c.) 2.4 mg once-weekly or semaglutide placebo once-weekly as adjunct to a reduced-calorie diet and increased physical activity
DRUGsemaglutide 2.4 mg (placebo)
semaglutide subcutanous (s.c.) 2.4 mg once-weekly or semaglutide placebo once-weekly as adjunct to a reduced-calorie diet and increased physical activity
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Male or female, age above or equal to 18 years at the time of signing informed consent * Body Mass Index (BMI) equal to or greater than 30.0 kg/m\^2 * Clinical diagnosis of knee OA (American College of Rheumatology (ACR) criteria) with moderate radiographic changes (Kellgren-Lawrence (KL) grades 2 or 3 as per central reading) in target knee. Target knee joint is defined as most symptomatic knee at screening. If pain in knees are equal target knee joint will be in the most dominant leg. * Pain due to knee OA
Exclusion criteria
* Joint replacement in target knee * Arthroscopy or injections into target knee within last 3 months prior to enrolment * Any other joint disease in the target knee
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Body Weight | Baseline (week 0), end of treatment (week 68) | Percentage change in body weight from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score | Baseline (week 0), end of treatment (week 68) | WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw pain score is derived as the sum of the 5 item scores in the pain domain. It will be normalised and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC Physical Function Score | Baseline (week 0), end of treatment (week 68) | Change in WOMAC physical function score is presented. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. WOMAC physical function is 17-item questionnaire used to assess degree of difficulty experienced due to OA in knee. It is calculated as the sum of the 17 item scores in the physical function domain. It is normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the physical function domain (i.e. 170) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in Short Form 36 (SF-36) Physical Functioning Score | Baseline (week 0), end of treatment (week 68) | SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary (including physical functioning, role-physical, bodily pain and general health) and mental component summary (including vitality, social functioning, role-emotional and mental health). Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in Waist Circumference | Baseline (week 0), end of treatment (week 68) | Change in waist circumference from baseline (week 0) to end of the treatment (visit 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in WOMAC Stiffness Score | Baseline (week 0), end of treatment (week 68) | WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw stiffness score is derived as the sum of the 2 item scores in the stiffness domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the stiffness domain (i.e. 20) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in WOMAC Total Score | Baseline (week 0), end of treatment (week 68) | WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. The WOMAC raw total score is derived as the sum of the 24 item scores respectively on pain, stiffness and physical function domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the total domain (i.e. 240) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in SF-36 Bodily Pain Score | Baseline (week 0), end of treatment (week 68) | Change in SF-36 Bodily Pain Score from baseline (week 0) to end of treatment (week 68) is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in SF-36 Physical Component Summary | Baseline (week 0), end of treatment (week 68) | Change in SF-36 physical component summary is presented. It is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Physical component summary contains physical functioning, role-physical, bodily pain and general health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in SF-36 Mental Component Summary | Baseline (week 0), end of treatment (week 68) | Change in SF-36 mental component summary is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: mental component summary and physical component summary. Mental component summary contain vitality, social functioning, role-emotional and mental health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No) | At end of treatment (week 68) | Percentage of participants using allowed rescue analgesics during wash out at end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have used allowed rescue analgesics during wash out whereas 'No' infers percentage of participants who have not used allowed rescue analgesics during wash out. Use of allowed rescue analgesics is evaluated based on use of acetaminophen reported in the pain medication diary from one up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Amount of Allowed Rescue Analgesics Used During Wash Out | At end of treatment (week 68) | Amount of allowed rescue analgesics used during wash out at end of treatment (week 68) is presented. Allowed rescue analgesic during washout is defined as acetaminophen taken 24-72 hour before the visit. The outcome measure is approximated by a total dose of acetaminophen reported in the pain medication diary from one and up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥ 5% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥5% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥5% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Change in Pain Intensity (Numerical Rating Scale [NRS]) | Baseline (week 0), end of treatment (week 68) | Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥15% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥15% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥15% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥20% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥20% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥20% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥30% WOMAC pain reduction (yes/no) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥30% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥50% WOMAC pain reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥50% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC pain score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 37.3 in the WOMAC pain score and it is derived based on 1-category improvement on patient global impression of status (PGI-S) scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores=worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC physical function score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 41.2 in the WOMAC physical function score and it is derived based on 1-category improvement on PGI-S scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved threshold for clinically meaningful within-participant change in SF-36 physical function score is presented. Threshold refers to increase of at least 11.4 in SF-36 physical functioning score & it is derived based on 1-category improvement on PGI-S scale. 'Yes' infers percentage of participants who achieved threshold; 'No' infers percentage of participants who have not achieved threshold. SF-36: self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, & general health perception. Each SF-36 domain and component summary score ranges from 0-100, higher scores mean better participant health status. Outcome measure was evaluated based on data from in-trial period: uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥30% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥30% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥50% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥50% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants With Use of Pain Medication | From baseline (week 0) to end of treatment (week 68) | Percentage of participants with use of pain medication from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
| Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No) | From baseline (week 0) to end of treatment (week 68) | Percentage of participants who achieved ≥10% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥10% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥10% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site. |
Countries
Canada, Colombia, Denmark, France, Norway, Russia, Saudi Arabia, South Africa, Spain, Sweden, United States
Participant flow
Recruitment details
The trial was conducted at 61 sites in 11 countries as follows (number of sites that screened participants/ number of sites that randomised participants): Canada (5/ 5); Colombia (3/ 3); Denmark (2/ 2); France (5/ 5); Norway (3/ 3); Russia (10/ 10); Saudi Arabia (4/ 4); South Africa (5/ 5); Spain (3/ 3); Sweden (4/ 4) and United States (17/ 17).
Pre-assignment details
The study included a screening visit followed by visits every 4th week during dose escalation period and every 8th week until end-of-treatment (week 68). Follow-up period was 7 weeks after end-of-treatment (week 75).
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 2.4 mg Participants initiated at a once-weekly dose of 0.24 mg semaglutide s.c. as a adjunct to a reduced calorie diet and increased physical activity and followed a fixed-dose escalation regimen, with dose increase every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), until the target dose was reached after 16 weeks. Participants continued 2.4 mg semaglutide s.c. once- weekly from week 16 to week 68 as a adjunct to a reduced calorie diet and increased physical activity. Participants were followed up for 7 weeks after end of treatment till week 75. | 271 |
| Placebo Participants received semaglutide matching placebo subcutaneously once weekly as a adjunct to a reduced calorie diet and increased physical activity from week 0 to week 68. Participants were followed up for 7 weeks after end of treatment till week 75. | 136 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Failing to Meet Randomization Requirements | 2 | 1 |
| Overall Study | Lost to Follow-up | 7 | 2 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Site Closure | 7 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide 2.4 mg |
|---|---|---|---|
| Age, Continuous | 56 Years STANDARD_DEVIATION 10 | 56 Years STANDARD_DEVIATION 10 | 56 Years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 56 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants | 328 Participants | 216 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 23 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 48 Participants | 37 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 22 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 31 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 26 Participants | 58 Participants | 32 Participants |
| Race (NIH/OMB) White | 80 Participants | 248 Participants | 168 Participants |
| Sex: Female, Male Female | 104 Participants | 332 Participants | 228 Participants |
| Sex: Female, Male Male | 32 Participants | 75 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 269 | 0 / 135 |
| other Total, other adverse events | 128 / 269 | 51 / 135 |
| serious Total, serious adverse events | 27 / 269 | 11 / 135 |
Outcome results
Primary
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score
WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw pain score is derived as the sum of the 5 item scores in the pain domain. It will be normalised and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score | -43.7 Score on a scale | Standard Deviation 25.3 |
| Placebo | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score | -26.2 Score on a scale | Standard Deviation 25 |
Comparison: The responses at week 68 were analyzed using an analysis of covariance model with randomized treatment as factor and baseline WOMAC pain score as covariate.p-value: <0.000195% CI: [-19.98, -8.3]ANCOVA
Primary
Percentage Change in Body Weight
Percentage change in body weight from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage Change in Body Weight | -14.2 Percentage change in body weight | Standard Deviation 8.6 |
| Placebo | Percentage Change in Body Weight | -2.5 Percentage change in body weight | Standard Deviation 5.6 |
Comparison: The responses at week 68 were analyzed using an analysis of covariance model with randomized treatment as factor and baseline body weight as covariate.p-value: <0.000195% CI: [-12.34, -8.63]ANCOVA
Secondary
Amount of Allowed Rescue Analgesics Used During Wash Out
Amount of allowed rescue analgesics used during wash out at end of treatment (week 68) is presented. Allowed rescue analgesic during washout is defined as acetaminophen taken 24-72 hour before the visit. The outcome measure is approximated by a total dose of acetaminophen reported in the pain medication diary from one and up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: At end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Amount of Allowed Rescue Analgesics Used During Wash Out | 224.2 Milligram | Standard Deviation 1756.4 |
| Placebo | Amount of Allowed Rescue Analgesics Used During Wash Out | 170.1 Milligram | Standard Deviation 1100.3 |
Secondary
Change in Pain Intensity (Numerical Rating Scale [NRS])
Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Pain Intensity (Numerical Rating Scale [NRS]) | -2.9 Score on a scale | Standard Deviation 2.7 |
| Placebo | Change in Pain Intensity (Numerical Rating Scale [NRS]) | -1.4 Score on a scale | Standard Deviation 2.4 |
Secondary
Change in SF-36 Bodily Pain Score
Change in SF-36 Bodily Pain Score from baseline (week 0) to end of treatment (week 68) is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in SF-36 Bodily Pain Score | 12.8 Score on a scale | Standard Deviation 9.4 |
| Placebo | Change in SF-36 Bodily Pain Score | 7.7 Score on a scale | Standard Deviation 10 |
Secondary
Change in SF-36 Mental Component Summary
Change in SF-36 mental component summary is presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: mental component summary and physical component summary. Mental component summary contain vitality, social functioning, role-emotional and mental health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in SF-36 Mental Component Summary | 1.9 Score on a scale | Standard Deviation 11.3 |
| Placebo | Change in SF-36 Mental Component Summary | 1.1 Score on a scale | Standard Deviation 11.6 |
Secondary
Change in SF-36 Physical Component Summary
Change in SF-36 physical component summary is presented. It is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary and mental component summary. Physical component summary contains physical functioning, role-physical, bodily pain and general health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in SF-36 Physical Component Summary | 13.2 Score on a scale | Standard Deviation 9.1 |
| Placebo | Change in SF-36 Physical Component Summary | 6.9 Score on a scale | Standard Deviation 9.3 |
Secondary
Change in Short Form 36 (SF-36) Physical Functioning Score
SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: physical component summary (including physical functioning, role-physical, bodily pain and general health) and mental component summary (including vitality, social functioning, role-emotional and mental health). Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline. The outcome measure was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Short Form 36 (SF-36) Physical Functioning Score | 12.7 Score on a scale | Standard Deviation 9.9 |
| Placebo | Change in Short Form 36 (SF-36) Physical Functioning Score | 6.4 Score on a scale | Standard Deviation 9.8 |
Secondary
Change in Waist Circumference
Change in waist circumference from baseline (week 0) to end of the treatment (visit 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Waist Circumference | -13.3 Centimeter | Standard Deviation 9.3 |
| Placebo | Change in Waist Circumference | -5.9 Centimeter | Standard Deviation 10.4 |
Secondary
Change in WOMAC Physical Function Score
Change in WOMAC physical function score is presented. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with osteoarthritis (OA). It consists of 3 subscales: pain, stiffness and physical function. WOMAC physical function is 17-item questionnaire used to assess degree of difficulty experienced due to OA in knee. It is calculated as the sum of the 17 item scores in the physical function domain. It is normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the physical function domain (i.e. 170) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in WOMAC Physical Function Score | -43.4 Score on a scale | Standard Deviation 25.5 |
| Placebo | Change in WOMAC Physical Function Score | -25.8 Score on a scale | Standard Deviation 25.1 |
Secondary
Change in WOMAC Stiffness Score
WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. It consists of 3 subscales: pain, stiffness and physical function. The WOMAC raw stiffness score is derived as the sum of the 2 item scores in the stiffness domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the stiffness domain (i.e. 20) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in WOMAC Stiffness Score | -45.4 Score on a scale | Standard Deviation 27.7 |
| Placebo | Change in WOMAC Stiffness Score | -27.6 Score on a scale | Standard Deviation 29.3 |
Secondary
Change in WOMAC Total Score
WOMAC is a disease-specific patient-reported outcome measure designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of the hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, participant-relevant symptoms in area of pain, stiffness, and physical function in participants with OA. The WOMAC raw total score is derived as the sum of the 24 item scores respectively on pain, stiffness and physical function domain. It will be normalized and expressed on a 0-100 scale. This is done by dividing raw score by the highest possible value of the raw score for the total domain (i.e. 240) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: Baseline (week 0), end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in WOMAC Total Score | -43.8 Score on a scale | Standard Deviation 24.9 |
| Placebo | Change in WOMAC Total Score | -26.0 Score on a scale | Standard Deviation 24.9 |
Secondary
Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No)
Percentage of participants who achieved ≥10% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥10% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥10% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No) | Yes | 70.4 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No) | No | 29.6 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No) | Yes | 9.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 10% (Yes/No) | No | 90.8 Percentage of participants |
Secondary
Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No)
Percentage of participants who achieved ≥15% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥15% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥15% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No) | Yes | 47.8 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No) | No | 52.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No) | Yes | 2.5 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 15% (Yes/No) | No | 97.5 Percentage of participants |
Secondary
Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No)
Percentage of participants who achieved ≥20% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥20% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥20% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No) | Yes | 23.3 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No) | No | 76.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No) | Yes | 0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction ≥ 20% (Yes/No) | No | 100 Percentage of participants |
Secondary
Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No)
Percentage of participants who achieved ≥ 5% body weight reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥5% weight reduction whereas 'No' infers percentage of participants who have not achieved ≥5% weight reduction. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No) | No | 13.0 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No) | Yes | 87.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No) | Yes | 29.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Body Weight Reduction Greater Than or Equal to (≥) 5 Percent (%) (Yes/No) | No | 70.8 Percentage of participants |
Secondary
Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No)
Percentage of participants who achieved ≥30% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥30% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No) | Yes | 64.8 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No) | No | 35.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No) | Yes | 39.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 30% (Yes/No) | No | 61.0 Percentage of participants |
Secondary
Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No)
Percentage of participants who achieved ≥50% pain intensity reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% pain intensity reduction whereas 'No' infers percentage of participants who have not achieved ≥50% pain intensity reduction. Response at visit was derived from the pain diary data as an average score over 4 days interval leading up to visit-related washout period for pain medication. Pain intensity was assessed on an 11-point NRS over the past 24 hours (before each specified visit), where a score of 0 indicated no pain and a score of 10 indicated worst possible pain, where higher the score, greater the pain intensity. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No) | Yes | 49.7 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No) | No | 50.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No) | Yes | 28.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving Pain Intensity (Numerical Rating Scale [NRS]) Reduction ≥ 50% (Yes/No) | No | 72.0 Percentage of participants |
Secondary
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No)
Percentage of participants who achieved threshold for clinically meaningful within-participant change in SF-36 physical function score is presented. Threshold refers to increase of at least 11.4 in SF-36 physical functioning score & it is derived based on 1-category improvement on PGI-S scale. 'Yes' infers percentage of participants who achieved threshold; 'No' infers percentage of participants who have not achieved threshold. SF-36: self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, & general health perception. Each SF-36 domain and component summary score ranges from 0-100, higher scores mean better participant health status. Outcome measure was evaluated based on data from in-trial period: uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No) | Yes | 60.6 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No) | No | 39.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No) | Yes | 28.7 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in SF-36 Physical Functioning Score (Yes/No) | No | 71.3 Percentage of participants |
Secondary
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No)
Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC pain score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 37.3 in the WOMAC pain score and it is derived based on 1-category improvement on patient global impression of status (PGI-S) scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores=worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No) | No | 38.8 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No) | Yes | 61.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No) | Yes | 33.3 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Pain Score (Yes/No) | No | 66.7 Percentage of participants |
Secondary
Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No)
Percentage of participants who achieved threshold for clinically meaningful within-participant change in WOMAC physical function score from baseline (week 0) to end of treatment (week 68) is presented. The threshold refers to the decrease of at least 41.2 in the WOMAC physical function score and it is derived based on 1-category improvement on PGI-S scale. In reported data, 'Yes' infers percentage of participants who have achieved threshold whereas 'No' infers percentage of participants who have not achieved threshold. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. Outcome measure was evaluated based on data from in-trial period and it was defined as uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No) | Yes | 54.1 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No) | No | 45.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No) | Yes | 29.1 Percentage of participants |
| Placebo | Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participant Change in WOMAC Physical Function Score (Yes/No) | No | 70.9 Percentage of participants |
Secondary
Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No)
Percentage of participants who achieved ≥30% WOMAC pain reduction (yes/no) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥30% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥30% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No) | Yes | 78.8 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No) | No | 21.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No) | Yes | 56.4 Percentage of participants |
| Placebo | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 30% (Yes/No) | No | 43.6 Percentage of participants |
Secondary
Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No)
Percentage of participants who achieved ≥50% WOMAC pain reduction (yes/no) from baseline (week 0) to end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have achieved ≥50% WOMAC pain reduction whereas 'No' infers percentage of participants who have not achieved ≥50% WOMAC pain reduction. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalized and expressed on 0-100 scale. This is done by dividing raw score by highest possible value of raw score for pain domain (i.e. 50) and multiplying by 100. Higher scores indicate worse outcome. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No) | No | 33.1 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No) | Yes | 66.9 Percentage of participants |
| Placebo | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No) | Yes | 34.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving WOMAC Pain Reduction ≥ 50% (Yes/No) | No | 65.8 Percentage of participants |
Secondary
Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No)
Percentage of participants using allowed rescue analgesics during wash out at end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of participants who have used allowed rescue analgesics during wash out whereas 'No' infers percentage of participants who have not used allowed rescue analgesics during wash out. Use of allowed rescue analgesics is evaluated based on use of acetaminophen reported in the pain medication diary from one up to 3 days prior to WOMAC assessment. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: At end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle. Here, Overall Number of Participants Analyzed = participants with available data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No) | Yes | 4.9 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No) | No | 95.1 Percentage of participants |
| Placebo | Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No) | No | 94.9 Percentage of participants |
| Placebo | Percentage of Participants Using Allowed Rescue Analgesics During Wash Out (Yes/No) | Yes | 5.1 Percentage of participants |
Secondary
Percentage of Participants With Use of Pain Medication
Percentage of participants with use of pain medication from baseline (week 0) to end of treatment (week 68) is presented. The outcome measure was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time frame: From baseline (week 0) to end of treatment (week 68)
Population: FAS included all randomized participants according to the intention-to-treat principle.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 2.4 mg | Percentage of Participants With Use of Pain Medication | Opioids | 8.5 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants With Use of Pain Medication | NSAID | 55.7 Percentage of participants |
| Semaglutide 2.4 mg | Percentage of Participants With Use of Pain Medication | Acetaminophen | 57.2 Percentage of participants |
| Placebo | Percentage of Participants With Use of Pain Medication | Acetaminophen | 58.1 Percentage of participants |
| Placebo | Percentage of Participants With Use of Pain Medication | Opioids | 9.6 Percentage of participants |
| Placebo | Percentage of Participants With Use of Pain Medication | NSAID | 59.6 Percentage of participants |