Dapiglutide for the Treatment of Obesity (DREAM)

Dapiglutide for the Treatment of Obesity (DREAM): a Randomised, Double-blind, Placebo-controlled, Investigator-initiated Trial

This study is an investigator-initiated, proof-of-concept, randomised, double-blind, placebo-controlled, parallel-group, single-centre clinical trial investigating the body weight loss potential of dapiglutide, a dual GLP-1R/GLP-2R agonist, administered subcutaneously once weekly. The study will investigate the efficacy of once-weekly subcutaneously administered of 4 mg and 6 mg dapiglutide versus placebo in 54 obese individuals (BMI >30 kg/m2) during a 12-week treatment period.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammation; Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Dapiglutide

Detailed Description

In total, 54 obese participants with a body mass index (BMI) of ≥ 30 kg/m² are randomised to either treatment with the investigational medicinal product (IMP), being either dapiglutide 4 mg, dapiglutide 6 mg, or placebo for 12 weeks. To ensure blinding, the placebo arm is split between 4 mg and 6 mg placebo, making the randomisation sequence 2:2:1:1. The trial encompasses a 3-week screening period containing a screening visit (V1) to assess eligibility, followed by a randomisation visit (V2) and subsequently a 12-week treatment period concluded with a 4-week follow-up period. The IMP is subcutaneously administered in the abdomen once weekly from week 0 (V2) until week 12 (V14). The IMP is initiated at 2 mg once-weekly and up-titrated every third week with 2 mg until the respective trial doses are reached in each arm. Hereafter, the participants are kept at the dose level for the remainder of the trial (from week 3 and week 6 for the 4 mg and 6 mg doses, respectively). To reduce dropout in cases of low tolerability of the IMP, the investigator can postpone up-titration or down-titrate if judged necessary for participant retention or safety. The trial schedule will consist of five on-site visits, including screening, randomisation and a safety follow-up visit (four weeks after end of treatment (EOT)), in addition to a minimum of 10 telephone consultations. Therefore, the maximum trial duration is 16 weeks. For exploratory purposes, participants are invited to participate in a gastroduodenoscopy sub-study obtaining gastric and duodenal biopsies before and after treatment with IMP. A maximum of 7 participants from each treatment arm (total n=21) participate in this sub-study.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Casper K Nielsen, MSc; Phone Number: +4560117434; Email: casper.kjaersgaard.nielsen@regionh.dk
• Study Contact Backup: Name: Filip K Knop, MD, PhD; Phone Number: +45 38674266; Email: filip.krag.knop.01@regionh.dk

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research, Herlev-Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-75 years
• BMI ≥ 30 kg/m²
• History of at least one attempt to lose body weight

Exclusion Criteria:

• A self-reported change in body weight ≥ 5% within the last 90 days prior to the screening visit
• Treatment with any therapy, including endoscopic procedures and/or medication (e.g. liraglutide, bupropion/naltrexone and orlistat), intended for weight management within 90 days prior to screening
• Previous, current, or planned (during the trial period) obesity treatment with surgery or a weight loss device < 1 year prior to screening
• Glycated haemoglobin (HbA1c) ≥ 48 mmol/mol
• History of type 1 diabetes or type 2 diabetes
• Treatment with glucose-lowering agents within 90 days prior to screening
• Compromised kidney function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2) at screening
• Known liver disease (except for non-alcoholic fatty liver disease) and/or elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal at screening
• History of acute and/or chronic pancreatitis
• History and/or family history of medullary carcinoma and/or multiple endocrine neoplasia syndrome
• Inflammatory bowel disease
• Any history of colon cancer or intestinal polyps
• Any history of intestinal stenosis
• History of any other cancers (except margin-free resected cutaneous basal or squamous cell carcinoma or adequately treated in situ cervical cancer) unless disease-free state for at least five years
• Uncontrolled thyroid disease as per discretion of the investigators
• Any of the following: myocardial infarction, stroke, hospitalisation for angina and transient ischaemic attack within the last 60 days prior to screening
• Class IV heart failure according to the New York Heart Association
• Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardise the participant's safety during the trial
• Alcohol/drug abuse as per discretion of the investigators
• Known or suspected hypersensitivity to the trial product or related products
• Previous treatment with the trial product
• Administration of an investigational drug within 90 days prior to screening
• Simultaneous participation in any other clinical intervention trial
• Mental incapacity or language barriers that preclude adequate understanding or cooperation, or unwillingness to comply with trial requirements
• Use of GLP-1RA, GLP-2RA, dipeptidyl peptidase 4 (DPP) inhibitors, human growth hormone, somatostatin, or analogues thereof, within three months prior to screening
• Known radiation enteritis or significant villous atrophy, e.g., due to active coeliac disease or inflammatory bowel disease

• Regarding fertile men and women:

  • Women who are pregnant, breastfeeding, intend to become pregnant or are of childbearing potential will not be included in the study
  • Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) can be included
  • The following contraceptive methods are considered adequate for study enrolment of male participants: Surgically sterilised or willing to refrain from sexual intercourse from screening and until completion of the follow-up visit, or, if sexually active, condom usage and partner-practised contraception during the trial, i.e., from screening to the last visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (4 mg and 6 mg); Abdominal s.c. self-administration of placebo content once weekly for 12 weeks. To ensure double-blinding, the placebo arm is divided into a 4-mg and 6-mg arm. But both placebo arms are pooled during data analysis.	Drug: Placebo; Placebo
Active Comparator: 4 mg dapiglutide; Abdominal s.c. self-administration of 4 mg dapiglutide once weekly initiated at 2 mg and up-titrated after three weeks until the remaining nine weeks of treatment (12 weeks in total)	Drug: Dapiglutide; GLP-1/GLP-2 receptor agonism; Other Names: ZP7570
Active Comparator: 6 mg dapiglutide; Abdominal s.c. self-administration of 6 mg dapiglutide once weekly initiated at 2 mg and up-titrated after three weeks to 4 mg and again to 6 mg after six weeks until the remaining six weeks of treatment (12 weeks in total)	Drug: Dapiglutide; GLP-1/GLP-2 receptor agonism; Other Names: ZP7570

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in body weight (kg)	%-point	From week 0 (baseline) to week 12 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight reduction ≥ 5%	count (yes/no)	From week 0 (baseline) to week 12 (end of treatment)
Body weight reduction ≥ 10%	count (yes/no)	From week 0 (baseline) to week 12 (end of treatment)
Change in fasting serum/plasma concentrations of gut permeability biomarker (LPS-binding protein (LBP))	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in fasting serum/plasma concentrations of inflammation markers (hs-CRP and IL-6)	%-point	From week 0 (baseline) to week 12 (end of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight reduction ≥ 15%	count (yes/no)	From week 0 (baseline) to week 12 (end of treatment)
Change in BMI (kg/m2)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in systolic blood pressure (mmHg)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in diastolic blood pressure (mmHg)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in resting heart rate (beats per minute)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in body composition as measured by bioimpedance	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in FibroScan®-assessed liver steatosis (dB/m)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in FibroScan®-assessed liver fibrosis (kPa)	%-point	From week 0 (baseline) to week 12 (end of treatment)
Change in Fatty liver index score (FLI)	%-point (FLI score: Range interval 0-100, < 30 negative likelihood of fatty liver and >60 positive likelihood of fatty liver)	From week 0 (baseline) to week 12 (end of treatment)
Change in fibrosis 4 score (FIB-4)	%-point (score of <1.30 = low risk; 1.30-2.67 = intermediate risk; >2.67 = high risk of advanced fibrosis)	From week 0 (baseline) to week 12 (end of treatment)
Change in the 36-Item Short Form Survey	Score points	From week 0 (baseline) to week 12 (end of treatment)
Change in IWQOL-Lite-CT	Score points	From week 0 (baseline) to week 12 (end of treatment)
Number of treatment-emergent AEs	Counts of events	From signed consent form (week -3) to follow-up visit (week 16)
Number of serious AEs (SAEs)	Counts of events	From signed consent form (week -3) to follow-up visit (week 16)

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: Zealand Pharma
• Investigators: Principal Investigator: Filip K Knop, MD, PhD, Center for Clinical Metabolic Research at Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2023
• Primary Completion (Estimated): April 8, 2024
• Study Completion (Estimated): August 15, 2024

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Gut barrier function
• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Inflammation
• Other Study ID Numbers: The 'DREAM' trial; 2022-501649-54-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this moment we do not plan to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No