Efficacy and safety of cagrilintide for weight management in participants with overweight or obesity

The primary objective of this trial is to confirm the superiority of subcutaneous cagrilintide 00 mg administered once weekly compared to placebo in achieving body weight reduction in participants with overweight or obesity, as an adjunct to lifestyle intervention counselling. Additionally, the primary objective includes confirming superiority of cagrilintide 00 mg versus placebo in achieving weight reduction of ≥ 5%. This objective addresses the clinical need for effective pharmacological interventions in weight management for individuals with elevated body mass index.

The secondary objectives of this trial are to evaluate multiple clinical and patient-centered outcomes. These include: confirming superiority of cagrilintide 00 mg versus placebo in achieving ≥ 10% and ≥ 15% weight reduction; confirming superiority of subcutaneous cagrilintide 00 mg once weekly versus placebo on waist circumference, triglycerides, high-sensitivity C-reactive protein (hsCRP), and physical functioning; comparing the effect of subcutaneous cagrilintide 00 mg once weekly versus placebo on body weight; comparing the effect on health-related quality of life and weight-related quality of life; comparing the effect on likelihood of achieving clinically relevant improvement in physical functioning; comparing the effect on blood pressure; comparing the effect on lipids; comparing the effect on glycaemic measures; and comparing the safety and tolerability of subcutaneous cagrilintide 00 mg once weekly versus placebo.

This clinical trial enrolled a total of **180 participants** with **overweight** or **obesity**. The study population included both **male** and **female** individuals aged **18 years or above**. Participants were selected based on specific eligibility requirements, including a **body mass index (BMI)** of at least **30.0 kg/m²**, or a BMI of at least **27.0 kg/m²** in the presence of at least one weight-related **comorbidity** such as **hypertension**, **dyslipidaemia**, **obstructive sleep apnoea**, or **cardiovascular disease**. All participants had a documented history of at least one unsuccessful dietary attempt to reduce body weight. The trial involved lifestyle intervention counselling as an adjunct to the investigational treatment. No vulnerable populations were included in this study.

This clinical trial investigates the efficacy and safety of **cagrilintide** for weight management in participants with **overweight** or **obesity**. The study is designed as a **randomized**, **placebo-controlled** trial evaluating **cagrilintide** administered as a **solution for injection** via the **subcutaneous** route once weekly compared to **placebo**, both provided as adjunct to lifestyle intervention counseling. The trial is classified as a **Phase III** clinical study. The maximum treatment period is 64 weeks. The estimated recruitment start date is November 5, 2025, with an anticipated end date of July 14, 2027.

The **primary endpoints** include the relative change in **body weight** and the achievement of at least 5% body weight reduction. **Secondary endpoints** encompass achievement of at least 10% and 15% body weight reductions, changes in **waist circumference**, ratios to baseline in **triglycerides** and **high-sensitivity C-reactive protein (hsCRP)**, changes in quality of life measures including the Impact of Weight on Quality of Life-Lite Clinical Trials Version Physical Function score and total score, changes in SF-36v2 Health Survey Acute physical and mental component summary scores, changes in **systolic** and **diastolic blood pressure**, ratios to baseline of various lipid parameters including **total cholesterol**, **HDL cholesterol**, **LDL cholesterol**, **VLDL cholesterol**, non-HDL cholesterol, and free fatty acids, changes in **glycated hemoglobin (HbA1c)** and **fasting plasma glucose**, ratios to baseline in fasting serum insulin, and the number of **treatment-emergent adverse events** and serious adverse events.

Principal **inclusion criteria** require that participants provide informed consent prior to any study-related activities. Eligible participants must be female or male (sex at birth), aged 18 years or above at the time of signing informed consent, and have a history of at least one self-reported unsuccessful dietary effort to lose body weight. Participants must have a **body mass index (BMI)** of at least 30.0 kg/m², or a BMI of at least 27.0 kg/m² with the presence of at least one weight-related **comorbidity** including, but not limited to, **hypertension**, **dyslipidemia**, **obstructive sleep apnea**, or **cardiovascular disease**.

The study involves a screening visit to assess eligibility, followed by randomization and initiation of treatment. Participants attend regular follow-up visits throughout the 64-week treatment period for safety monitoring, efficacy assessments, and collection of biological samples. An end-of-study visit is conducted upon completion of the treatment period or in the event of early termination. Early termination from the study may occur due to participant withdrawal of consent, safety concerns, protocol violations, or other conditions as determined by the investigator or sponsor.

The experimental medication under investigation is cagrilintide, a synthetically produced protein-based therapeutic agent. Cagrilintide is also known by its synonyms NNC0174-0833, NN9838, and its chemical designation N-alfa-[(S)-4-Carboxy-4-(19-carboxynonadecanoylamino)butyryl]-[Glu14,Arg17,Pro25,Pro28,Pro29,Pro37]-human amylin. The active substance is classified as a protein of other origin. The investigational medicinal product is supplied as a solution for injection in multiple formulations. The route of administration for cagrilintide is subcutaneous injection. The treatment period extends up to 64 weeks. The dosage is expressed in milligrams, though specific dose amounts are not detailed in the available data. Cagrilintide is administered as an adjunct to lifestyle intervention counselling for weight management in participants with overweight or obesity.

A placebo comparator is utilized in this clinical trial. The placebo serves as the control treatment against which the efficacy and safety of cagrilintide is evaluated. Participants receiving placebo also undergo lifestyle intervention counselling concurrent with treatment administration. The study design incorporates placebo to confirm superiority of cagrilintide on body weight reduction and achievement of weight loss targets.

Efficacy will be assessed using multiple parameters to evaluate the effect of cagrilintide on weight management in participants with overweight or obesity. The primary endpoints include relative change in body weight and achievement of at least 5% body weight reduction. Secondary endpoints encompass achievement of at least 10% and at least 15% body weight reduction, change in waist circumference, and absolute change in body weight. Additional secondary efficacy parameters include changes in lipid profiles measured as ratio to baseline in triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, non-HDL cholesterol, and free fatty acids. Inflammatory markers will be assessed through ratio to baseline in hsCRP. Glycemic parameters include change in glycated haemoglobin and change in fasting plasma glucose, as well as ratio to baseline in fasting serum insulin. Cardiovascular parameters comprise change in systolic blood pressure and change in diastolic blood pressure. Quality of life and functional outcomes will be evaluated through change in Impact of Weight on Quality of Life-Lite Clinical Trials Version Physical Function score, achievement of at least 14.6-point increase in IWQOL-Lite-CT Physical Function score, change in IWQOL-Lite-CT total score, change in SF-36v2® Health Survey Acute physical component summary score, and change in SF-36v2® mental component summary score. Safety will be monitored through the number of treatment emergent adverse events and the number of treatment emergent serious adverse events.