Obesity

Primary objective: • To demonstrate the superiority of CagriSema 2.4 mg/2.4 mg (administered subcutaneously once weekly) versus placebo and/or cagrilintide 2.4 mg (administered subcutaneously once weekly) versus placebo in weight management (parallel testing) Secondary objectives: • To demonstrate the superiority of CagriSema 2.4 mg/2.4 mg (administered subcutaneously once weekly) versus placebo and/or cagrilintide 2.4 mg (administered subcutaneously once weekly) versus placebo in weight management* (parallel testing) • To demonstrate the superiority of CagriSema 2.4 mg/2.4 mg (administered subcutaneously once weekly) versus semaglutide 2.4 mg (administered subcutaneously once weekly) in weight management • To demonstrate the superiority of CagriSema 2.4 mg/2.4 mg (administered subcutaneously once weekly) versus placebo in weight management • To demonstrate the superiority of cagrilintide 2.4 mg (administered subcutaneously once weekly) versus placebo in weight management

Cagrilintide
CagriSema
Semaglutide

Cagrilintide B
Cagrilintide B /Semaglutide I
Semaglutide

Subcutaneous injection
Subcutaneous injection
Subcutaneous injection

0.5, 1.0, 1.7, 2.4 6
0.25/ 0.25 mg; 0.5/ 0.5 mg; 1.0/ 1.0mg; 1.7 /1.7mg; 2.4/ 2.4 mg
0.25, 0.5, 1.0, 1.7, 2.4 mg

To evaluate the relative change in body mass index (BMI) from baseline (Week 0) to the end of treatment (Week 68) with once-weekly subcutaneous CagriSema 2.4 mg/2.4 mg versus placebo* and/or once-weekly subcutaneous Cagrilintide 2.4 mg versus placebo.

Key inclusion criteria:
1. Informed consent obtained from the participant's parent or legally authorized representative (LAR) and assent obtained from the child (depending on age) prior to any trial-related activities. Trial-related activities refer to any procedures performed as part of the trial, including activities to determine eligibility for participation.
a. The child's parent or LAR must sign and date the informed consent form (in accordance with local requirements).
b. The child must sign and date the child assent form or provide verbal assent (in accordance with local requirements).
2. Male or female.
3. Aged 8 to < 18 years at the time of signing the informed consent form.
4. Body Mass Index (BMI) at screening equivalent to:
a. For children aged 8 to < 12 years (Tanner stages 1–5): ≥ 95th percentile.
b. For adolescents aged 12 to < 18 years (Tanner stages 2–5): ≥ 95th percentile, or ≥ 85th percentile with at least one obesity-related complication, including but not limited to type 2 diabetes (T2D), hypertension, dyslipidemia, or obstructive sleep apnea.
5. Laboratory parameters measured by the central laboratory at screening (total calcium, phosphate, alkaline phosphatase, parathyroid hormone) are within the normal sex- and age-specific ranges.
6. History of at least one unsuccessful attempt to lose sufficient weight after participating in a structured lifestyle modification program (diet and exercise counseling) for at least 3 months.
7. Body weight > 45 kg at screening.
For participants with T2D at screening, the following inclusion criteria also apply:
8. Glycated hemoglobin (HbA1c) measured by the central laboratory at screening is ≤ 10.0% (86 mmol/mol).
9. Receiving lifestyle intervention or metformin therapy in accordance with the local package insert. Metformin treatment should be maintained at a stable level (same dose and dosing frequency) for at least 56 days prior to screening.

主要排除條件:
1.篩選前 90 天內曾依處方接受任何肥胖或體重管理藥物的治療。
2.先前或預定（在試驗期間）接受手術或減重器材的肥胖治療。然而，允許以下情況：
a.抽脂和/或腹部整形術，若在篩選前 > 1 年進行。
b.可調式胃束帶，若已在篩選的 > 1 年前移除束帶。
c.胃內水球，若已在篩選的 > 1 年前移除水球。
d.十二指腸空腸旁路襯墊（例如：Endobarrier），若已在篩選的 > 1 年前移除套管。
3.控制不良的甲狀腺疾病。
4.內分泌、下視丘或症候群性肥胖。
5.篩選前 90 天內自我報告（或由父母/LAR 報告，如適用）體重變化 > 5%，不論病歷內容為何。
6.第 1 型糖尿病或單基因糖尿病。
針對篩選時未患有 T2D 的參與者，下列排除條件也適用
7.篩選時中央實驗室測量的 HbA1c ≥ 6.5% (≥ 48 mmol/mol)。
8.在篩選前 90 天內，曾為糖尿病或糖尿病前期適應症開立降血糖藥物的治療。

針對篩選時患有 T2D 的參與者，下列排除條件也適用
9.試驗主持人根據 Clarke 問卷問題 8 判定已知有低血糖意識喪失。
10.由試驗主持人判定篩選前 1 年內曾發生復發性嚴重低血糖事件。
11.胰島素瘤相關蛋白 2 (IA-2) 抗體或抗麩胺酸脫羧酶（anti-GAD）抗體呈陽性。
12.篩選前 90 天內曾為納入條件所述之外的糖尿病適應症接受任何藥物治療。
13.控制不良且具有潛在不穩定性的糖尿病視網膜病變或黃斑部病變。依據篩選前 90 天內或篩選與隨機分配之間期間進行的眼底檢查加以驗證。必須進行藥物散瞳，除非使用非散瞳檢查專用的數位眼底攝影相機。