Clinical trial NCT05788601: Dapiglutide for the Treatment of Obesity
Official title: Dapiglutide for the Treatment of Obesity (DREAM): a Randomised, Double-blind, Placebo-controlled, Investigator-initiated Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Obesity
Inflammation
Keywords: Gut barrier function
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: Zealand Pharma
First posted: 2023-03-29
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three arms: 12 weeks of 4 mg and 6 mg dapiglutide and placebo
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage change in body weight (kg)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
Secondary outcomes:
measure: Body weight reduction ≥ 5%
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Body weight reduction ≥ 10%
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in fasting serum/plasma concentrations of gut permeability biomarker (LPS-binding protein (LBP))
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in fasting serum/plasma concentrations of inflammation markers (hs-CRP and IL-6)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
Other outcomes:
measure: Body weight reduction ≥ 15%
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in BMI (kg/m2)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in systolic blood pressure (mmHg)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in diastolic blood pressure (mmHg)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in resting heart rate (beats per minute)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in body composition as measured by bioimpedance
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in FibroScan®-assessed liver steatosis (dB/m)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in FibroScan®-assessed liver fibrosis (kPa)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in Fatty liver index score (FLI)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in fibrosis 4 score (FIB-4)
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in the 36-Item Short Form Survey
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Change in IWQOL-Lite-CT
timeFrame: From week 0 (baseline) to week 12 (end of treatment)
measure: Number of treatment-emergent AEs
timeFrame: From signed consent form (week -3) to follow-up visit (week 16)
measure: Number of serious AEs (SAEs)
timeFrame: From signed consent form (week -3) to follow-up visit (week 16)
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Herlev-Gentofte Hospital
Study officials:
affiliation: Center for Clinical Metabolic Research at Gentofte Hospital
name: Filip K Knop, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: