Clinical Trial Results:
Effect and safety of semaglutide 2.4 mg once weekly on weight management in adolescents with overweight or obesity
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Summary
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EudraCT number |
2018-002431-18 |
Trial protocol |
GB AT BE IE HR |
Global end of trial date |
28 Mar 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Sep 2022
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First version publication date |
03 Sep 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN9536-4451
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04102189 | ||
WHO universal trial number (UTN) |
U1111-1215-7560 | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001441-PIP03-17 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 May 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Mar 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the effect of semaglutide subcutaneously (s.c.) once-weekly versus semaglutide placebo as an adjunct to a reduced-calorie diet and increased physical activity on weight management in adolescents (ages 12 to less than [<18] years) with overweight or obesity
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Protection of trial subjects |
This trial was conducted in accordance with the principles of the Declaration of Helsinki (2013), International Council for Harmonisation (ICH) Good Clinical Practice, including the archiving of essential documents (2016), and US Food and Drug Administration (FDA) 21 Code of Federal Regulations (CFR) 312.120. The FDA 21 CFR, parts 312, 50, and 56 were followed.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
07 Oct 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 11
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Country: Number of subjects enrolled |
Belgium: 24
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Country: Number of subjects enrolled |
United Kingdom: 22
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Country: Number of subjects enrolled |
Croatia: 16
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Country: Number of subjects enrolled |
Ireland: 4
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Country: Number of subjects enrolled |
Mexico: 18
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Country: Number of subjects enrolled |
Russian Federation: 55
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Country: Number of subjects enrolled |
United States: 51
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Worldwide total number of subjects |
201
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EEA total number of subjects |
55
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
201
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was conducted at 37 sites in 8 countries, as follows: Austria (3), Belgium (4), Croatia (3), Ireland (1), Mexico (1), Russia (7), Great Britain (6), United States (12). | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects were randomised 2:1 to receive either semaglutide s.c. once weekly or semaglutide placebo s.c. once weekly for a dose escalation period of 16 weeks and a maintenance period of 52 weeks. This was followed by a 7-week follow-up period after ‘end of treatment’ due to the long half-life of semaglutide. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Blinding implementation details |
The clinical study group and the investigator were blinded throughout the trial.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Semaglutide 2.4 mg | ||||||||||||||||||||||||
Arm description |
Subjects received once weekly s.c. injection of semaglutide for 68 weeks. Subjects initially received 0.25 mg of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Semaglutide
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Investigational medicinal product code |
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Other name |
Wegovy
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects initially received 0.25 mg of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). Injections were administered in the thigh, abdomen or upper arm at any time of day irrespective of meals.
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Subjects received once weekly s.c. injection of semaglutide matching placebo for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received once weekly s.c. injection of semaglutide matching placebo for 68 weeks. Injections were administered in the thigh, abdomen or upper arm at any time of day irrespective of meals.
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Baseline characteristics reporting groups
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Reporting group title |
Semaglutide 2.4 mg
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Reporting group description |
Subjects received once weekly s.c. injection of semaglutide for 68 weeks. Subjects initially received 0.25 mg of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received once weekly s.c. injection of semaglutide matching placebo for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Semaglutide 2.4 mg
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Reporting group description |
Subjects received once weekly s.c. injection of semaglutide for 68 weeks. Subjects initially received 0.25 mg of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects received once weekly s.c. injection of semaglutide matching placebo for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity. | ||
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End point title |
Change in body mass index (BMI) from baseline | ||||||||||||
End point description |
Change in percentage of BMI from baseline at week 68 is presented. Full analysis set (FAS) included all randomised subjects according to the intention-to-treat principle. 'Number of Subjects Analyzed' signifies number or subjects evaluable for this endpoint. Data is presented for in-trial period: the in-trial period was defined as the uninterrupted time interval from randomisation to last contact with trial site.
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End point type |
Primary
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End point timeframe |
Baseline (week 0), week 68
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Statistical analysis title |
Semaglutide 2.4 mg vesrus Placebo | ||||||||||||
Statistical analysis description |
Week 68 responses were analysed using an analysis of covariance model with randomised treatment, stratification groups (sex and tanner stage at baseline)
and the interaction between stratification groups as factors and baseline BMI as covariate. All subjects in FAS (201 subjects) contributed to the analysis.
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Comparison groups |
Placebo v Semaglutide 2.4 mg
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Number of subjects included in analysis |
193
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Treatment difference | ||||||||||||
Point estimate |
-16.75
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-20.27 | ||||||||||||
upper limit |
-13.23 | ||||||||||||
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End point title |
Subjects achieving equal to or above 5% reduction of body weight from baseline (yes/no) | |||||||||||||||
End point description |
Number of subjects who achieved equal to or above 5% reduction in body weight from baseline to 68 weeks is presented. In the reported data, 'Yes' infers the number of subjects who achieved equal to or above 5% weight reduction, whereas 'No' infers the number of subjects who have not achieved equal to or above 5% weight reduction. FAS included all randomised subjects according to the intention-to-treat principle. 'Number of Subjects Analyzed' signifies number or subjects evaluable for this endpoint. Data is presented for in-trial period: the in-trial period was defined as the uninterrupted time interval from randomisation to last contact with trial site.
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End point type |
Secondary
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End point timeframe |
Baseline (week 0) to week 68
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Adverse events information
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Timeframe for reporting adverse events |
From baseline (week 0) to week 75
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Adverse event reporting additional description |
All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAEs: AEs with if onset of event occurred in on-treatment period . On-treatment period: interval from first to last trial product administration plus 7 weeks. Safety analysis set included all randomised subjects exposed to at least 1 dose of randomised treatment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24
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Reporting groups
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Reporting group title |
Semaglutide 2.4 mg
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Reporting group description |
Subjects were initiated at a once-weekly dose of 0.25 mg semaglutide s.c. and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week) until maintenance dose (2.4 mg) was reached in dose escalation period of 16 weeks. Subjects continued the maintenance dose of semaglutide 2.4 mg in maintenance period of 52 weeks. Subjects were followed up for 7 weeks after the ‘end of treatment’. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received semaglutide placebo once weekly for dose escalation period of 16 weeks followed by a maintenance period of 52 weeks. Subjects were followed up for 7 weeks after the ‘end of treatment’. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/35797460 |
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