NN9536-4578

Novo Nordisk A/S

Novo Allé, Bagsvaerd, Denmark, 2880

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com

No

No

No

Final

17 Nov 2023

No

Yes

08 Sep 2023

No

To confirm superiority of semaglutide subcutaneous (s.c.; under the skin) 2.4 mg once-weekly versus semaglutide placebo as an adjunct to a reduced-calorie diet and increased physical activity in subjects with obesity and knee osteoarthritis (OA) in change from baseline to week 68 in body weight and knee OA-related pain.

This study was conducted in accordance with the principles of the Declaration of Helsinki, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice including the archiving of essential documents and US Food and Drug Administration (FDA) 21 US Code of Federal Regulations (CFR) 312.120 and FDA 21 CFR 312.120, 50, and 56.

01 Oct 2021

No

No

Canada: 22

Spain: 31

France: 21

Sweden: 30

Russian Federation: 77

United States: 68

South Africa: 51

Colombia: 47

Saudi Arabia: 25

Norway: 16

Denmark: 19

407

117

0

0

0

0

0

0

330

77

0

Overall Study (overall period)

Randomised - controlled

Yes

Semaglutide

Solution for injection

Subcutaneous use

Subjects received semaglutide 2.4 mg once weekly by subcutaneous injection (in the abdomen, thigh or upper arm).

Placebo

Solution for injection

Subcutaneous use

Subjects received placebo matched to semaglutide once weekly by subcutaneous injection (in the abdomen, thigh or upper arm).

Semaglutide 2.4 mg

Placebo

Semaglutide 2.4 mg

Placebo

Percentage change in body weight from baseline (week 0) to end of treatment (week 68) is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, Number of subjects Analysed (N) = subjects with available data for this endpoint.

Primary

From baseline (week 0) to end of treatment (week 68)

The responses at week 68 were analysed using an analysis of covariance model with randomised treatment as factor and baseline body weight as covariate.

Semaglutide 2.4 mg v Placebo

373

Pre-specified

-10.48

2-sided

WOMAC: disease-specific subject-reported endpoint designed to assess changes in symptoms and lower extremity functioning associated with treatment in subjects with osteoarthritis (OA) of hip and/or knee. It’s a 24-item questionnaire to assesses clinically important, subject-relevant symptoms in area of pain, stiffness, and physical function in subject with OA. It consists of 3 subscales: pain, stiffness and physical function. WOMAC raw pain score is derived as sum of 5 item scores in pain domain. It will be normalised 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. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS:all randomised subjects according to intention-to-treat principle. Here, N =subjects with available data for this endpoint.

Primary

From baseline (week 0) to end of treatment (week 68)

The responses at week 68 were analysed using an analysis of covariance model with randomised treatment as factor and baseline WOMAC pain score as covariate.

Semaglutide 2.4 mg v Placebo

362

Pre-specified

-14.14

2-sided

Percentage of subjects 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 subjects who have achieved ≥5% weight reduction whereas 'No' infers percentage of subjects who have not achieved ≥5% weight reduction. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

Percentage of subjects 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 subjects who have achieved ≥10% weight reduction whereas 'No' infers percentage of subjects who have not achieved ≥10% weight reduction. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

WOMAC is 24 item questionnaire which assesses clinically important, subject -relevant symptoms in area of pain, stiffness, and physical function in subjects 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 sum of 17 item scores in physical function domain. It is normalized and expressed on a 0-100 scale. This is done by dividing raw score by highest possible value of raw score for physical function domain (i.e. 170) and multiplying by 100. Higher scores indicate worse outcome. Endpoint was evaluated based on data from in-trial period. In-trial period was defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

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, and general health perception. There are also 2 component scores derived from 8 subscale scores: physical component summary (physical functioning, role-physical, bodily pain and general health) and mental component summary (vitality, social functioning, role-emotional and mental health). Each SF-36 domain and component summary score ranges from 0-100, higher scores reflect better subject health status. Positive change score=improvement since baseline. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS: all randomised subjects according to intention-to-treat principle. Here, N=subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

Change in waist circumference from baseline (week 0) to end of the treatment (visit 68) is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

WOMAC: disease-specific subject-reported endpoint designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with OA of hip and/or knee. It’s a 24 item questionnaire which assesses clinically important, subject-relevant symptoms in area of pain, stiffness, and physical function in subjects with OA. It consists of 3 subscales: pain, stiffness and physical function. WOMAC raw stiffness score is derived as sum of 2 item scores in stiffness 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 stiffness domain (i.e. 20) and multiplying by 100. Higher scores=worse outcome. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS: all randomised subjects according to intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

WOMAC is a disease-specific patient-reported endpoint designed to assess changes in symptoms and lower extremity functioning associated with treatment in patients with osteoarthritis of hip and/or knee. WOMAC is a 24 item questionnaire which assesses clinically important, subject-relevant symptoms in area of pain, stiffness, and physical function in subjects with OA. WOMAC raw total score is derived as sum of 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 highest possible value of raw score for total domain (i.e. 240) and multiplying by 100. Higher scores indicate worse outcome. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS:all randomised subjects according to intention-to-treat principle. Here, N =subjects with available data for this endpoint.

Secondary

From baseline (week 0) to 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. Also 2 component scores derived from 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 health status. A positive change score indicates an improvement since baseline. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS: all randomised subjects according to intention-to-treat principle. Here, N =subjects with available data for this endpoint.

Secondary

From baseline (week 0) to 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, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. Also 2 component scores derived from 8 subscale scores: physical component summary and mental component summary. Physical component summary: physical functioning, role-physical, bodily pain and general health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores=better subject health status. Positive change score=improvement since baseline. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS: all randomised subjects according to intention-to-treat principle. Here, N=subjects with available data for this endpoint.

Secondary

From baseline (week 0) to 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, social functioning, bodily pain, mental health, role limitations due to emotional problems, vitality, and general health perception. Also 2 component scores derived from 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 0-100, higher scores= better subject health status. Positive change score= improvement since baseline. Endpoint was reported for in-trial period, defined as uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS: all randomised subjects according to intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

Percentage of subjects using allowed rescue analgesics during wash out at end of treatment (week 68) is presented. In the reported data, 'Yes' infers percentage of subjects who have used allowed rescue analgesics during wash out whereas 'No' infers percentage of subjects 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 endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to 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 endpoint 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 endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

From baseline (week 0) to end of treatment (week 68)

Percentage of subjects with use of pain medication from baseline (week 0) to end of treatment (week 68) is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle.

Secondary

From baseline (week 0) to 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 endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. FAS included all randomised subjects according to the intention-to-treat principle. Here, N= subjects with available data for this endpoint.

Secondary

Baseline (week 0), end of treatment (week 68)

From baseline (week 0) to end of trial (week 75)

Treatment-emergent adverse events defined as event with onset during on-treatment period (date of 1st trial product use to date of last trial product use excluding potential off-treatment time intervals triggered by at least 2 consecutive missed doses) presented. SAS: all randomised subjects exposed to at least 1 dose of randomised treatment.

26

Placebo

Sema 2.4 mg