A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adolescents With Type 2 Diabetes

Phase 3RecruitingNCT07282613

Novo Nordisk A/S80 enrolled

Overview

The purpose of this clinical study is to look into how well a study medicine called CagriSema helps children and adolescents living with diabetes lower their blood sugar and body weight. The study has 2 parts: in the first part participant will get either CagriSema or placebo, and in the second part participant will get CagriSema. In the first part, which treatment participant gets is decided by chance and second part is open label and all participants will get CagriSema during this part. The study will last for about 1 year and 3 months.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Diabetes Mellitus, Type 2

Interventions

CagriSema (Cagrilintide B and Semaglutide I)

Eligibility

Sex: ALLMin age: 10 YearsMax age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Informed consent of parent(s) or legally acceptable representative (LAR) of participant and child assent, as age-appropriate, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. * The parent(s) or LAR of the child must sign and date the Informed Consent Form (according to local requirements) * The child must sign and date the Child Assent Form or provide oral assent (according to local requirements) * Male or female. * Age 10 to \< 18 years at the time of signing the informed consent. * Diagnosed with T2D (according to the latest International Society for Pediatric and Adolescent Diabetes \[ISPAD\] criteria) ≥ 30 days before screening. * Treated with diet and exercise counselling alone or with a stable daily dose(a), in addition to diet and exercise counselling, of any of the following antidiabetic drugs or combination regimens: * Insulin (any regimen) * Metformin * SGLT2i * HbA1c 6.5%-11.0% (48 mmol/mol - 97 mmol/mol) (both inclusive) as determined by central laboratory at screening. * Body weight ≥ 45 kg and BMI ≥ 85th percentile(b). BMI will be calculated in the electronic case report form based on height and body weight at screening. * (a) For metformin, a stable dose is defined as at least 1000 mg daily or the maximum tolerated dose for ≥ 56 days prior to screening. For Sodium-Glucose Transport protein 2 inhibitor (SGLT2i), a stable dose is defined as the same total daily dose for ≥ 56 days prior to screening. For insulin, it is defined as the dose ± 25% of that taken at screening for ≥ 30 days prior to screening. * (b) Based on sex-specific BMI-for-age percentiles for the given country or region. If not available for the country or region, the respective charts or tables on cdc.gov may be used. Key Exclusion Criteria: * Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method. * Treatment with any antidiabetic or anti-obesity medication (irrespective of indication) other than stated in the inclusion criteria within 90 days before screening. * Known or previous diagnosis of hypoparathyroidism. * Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed \>1 year before screening, (2) lap banding, if the band has been removed \>1 year before screening, (3) intragastric balloon, if the balloon has been removed \>1 year before screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed \> 1 year before screening. * Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies as determined by central laboratory at screening or in medical history. * Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator. * Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8. * Uncontrolled and potentially unstable diabetic retinopathy maculopathy. Verified by a fundus examination and optical coherence tomography (OCT) assessment performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Outcomes

Primary Outcomes

Change in glycated haemoglobin (HbA1c)

Measured as percentage (%) of HbA1c.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Secondary Outcomes

Relative change in body mass index (BMI)

Measured as percentage.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with achievement of HbA1c target values of less than (<) 7.0% (< 53 millimole per mole [mmol/mol])

Measured as count of participants.

Time frame: At end of double-blinded treatment (week 26)

Number of participants with achievement of HbA1c target values of less than or equal to (≤) 6.5% (≤48 mmol/mol)

Measured as count of participants.

Time frame: At end of double-blinded treatment (week 26)

Change in time in range (TIR) 3.9-10.0 millimole per liter (mmol/L) (70-180 milligram per deciliter (mg/dL) measured using continuous glucose monitoring (CGM)

Measured as percentage of time.

Time frame: From baseline (collected during week -3, -2 and -1) to end-of-double-blinded treatment (collected during week 22, 23, 24, and 25)

Change in time in tight target range (TITR) 3.9-7.8 mmol/L (70-140 mg/dL) measured using CGM

Measured as percentage of time.

Time frame: From baseline (collected during week -3, -2 and -1) to end-of-double-blinded treatment (collected during week 22, 23, 24, and 25)

Change in time above range (TAR) greater than (>) 10.0 mmol/L (> 180 mg/dL) measured using CGM

Measured as percentage of time.

Time frame: From baseline (collected during week -3, -2 and -1) to end-of-double-blinded treatment (collected during week 22, 23, 24, and 25)

Change in TAR greater than (>) 13.9 mmol/L (> 250 mg/dL) measured using CGM

Measured as percentage of time.

Time frame: From baseline (collected during week -3, -2 and -1) to end-of-double-blinded treatment (collected during week 22, 23, 24, and 25)

Change in mean sensor glucose concentration measured by CGM

Measured as mmol/L.

Time frame: From baseline (collected during week -3, -2 and -1) to end-of- double-blinded treatment (collected during week 22, 23, 24, and 25)

CGM: Within-day glycaemic variability (% coefficient of variation)

Measured as percentage.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with incidence of glycaemic rescue therapy

Measured as count of participants

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in fasting plasma glucose

Measured as mmol/L.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with achievement of greater than or equal to (≥) 5% BMI reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with achievement of ≥ 10% BMI reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with achievement of ≥ 15% BMI reduction

Measured as count of participants.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Relative change in body weight

Measured as percentage of body weight.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in BMI standard deviation score (SDS)

Measured as score on scale.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in waist circumference

Measured as centimetre (cm).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in waist-to-height ratio

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in systolic blood pressure

Measured as millimetre of mercury (mmHg).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in diastolic blood pressure

Measured as mmHg.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: total cholesterol

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: high density lipoprotein (HDL) cholesterol

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: low density lipoprotein (LDL) cholesterol

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: very low density lipoprotein (VLDL) cholesterol

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: triglycerides

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in lipid: Non-HDL cholesterol

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in alanine aminotransferase (ALT)

Measured as units per liter (U/L).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26) and end of extension phase treatment (week 52)

Apparent clearance (CL/F) of cagrilintide and semaglutide

Measured as liter per hour (L/h).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Average concentration (Cavg) of cagrilintide and semaglutide at steady state

Measured as nanomole per liter (nmol/L).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in insulin dose

Measured as units (U).

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of participants with achievement of sustained insulin dose = 0 U

Measured as count of participants.

Time frame: At end of double-blinded treatment (week 26)

Ratio to baseline in urine albumin-creatinine ratio (UACR)

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in biomarker related to glucose metabolism: fasting C-peptide

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in biomarker related to glucose metabolism: fasting insulin

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in biomarker related to glucose metabolism: fasting proinsulin

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in biomarker related to glucose metabolism: fasting glucagon

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in high sensitivity C-reactive protein (hsCRP)

Measured as ratio.

Time frame: From baseline (week 0) to end of double- blinded treatment (week 26)

Ratio to baseline in free fatty acids

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in leptin

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in soluble leptin receptor

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Ratio to baseline in leptin to soluble leptin receptor ratio

Measured as ratio.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in aspartate aminotransferase (AST)

Measured as U/L.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26) and end of extension phase treatment (week 52)

Change in alkaline phosphatase (ALP)

Measured as U/L.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26) and end of extension phase treatment (week 52)

Change in bilirubin

Measured as U/L.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26) and end of extension phase treatment (week 52)

Change in HbA1c

Measured as percentage of HbA1c.

Time frame: From baseline (week 0) to end of extension phase treatment (week 52)

Number of clinically significant hypoglycaemic episodes (level 2) (< 3.0 mmol/L (54 mg/dL) confirmed by blood glucose [BG] meter)

Measured as count of episodes.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Number of severe hypoglycaemic episodes (level 3) - severe hypoglycaemia being defined as severe cognitive impairment requiring assistance by another person to administer carbohydrates, glucagon, or intravenous glucose

Measured as count of episodes.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Change in percentage of time below range (TBR) < 3.0 mmol/L (< 54 mg/dL) measured using CGM

Measured as percentage of time.

Time frame: At end of double-blinded treatment (collected during week 22, 23, 24, and 25)

Change in TBR < 3.9 mmol/L (< 70 mg/dL) measured using CGM

Measured as percentage of time.

Time frame: At end of double-blinded treatment (collected during week 22, 23, 24, and 25)

Number of treatment-emergent adverse events

Measured as count of events.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

Height velocity

Measured as cm/year.

Time frame: At end of double-blinded treatment (week 26)

Change in height SDS

Measured as score on scale.

Time frame: From baseline (week 0) to end of double-blinded treatment (week 26)

A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adolescents With Type 2 Diabetes

Overview

Conditions

Interventions

Eligibility

Locations (58)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts