ORISMILAST for Obesity

Inclusion criteria

• {"criterion_text":"- Age 18-75\n- BMI ≥ 30 kg/m²\n- History of at least one attempt to lose body weight"}

Exclusion criteria

• {"criterion_text":"- A self-reported change in body weight ≥ 5% within the last three months prior to the screening visit\n- History of major depressive disorder within 2 years of screening\n- Unstable severe psychiatric disorder (e.g. bipolar disorder or schizophrenia)\n- Suicidal behaviour three months prior to screening visit\n- Any prior suicidal attempt\n- Class IV heart failure, according to the New York Heart Association\n- Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardise the participant’s safety during the trial\n- Alcohol/drug abuse as per discretion of the investigators\n- Known or suspected hypersensitivity to orismilast, semaglutide or related products\n- Administration of any investigational drug within three months prior to the screening visit\n- Simultaneous participation in any other clinical intervention trial until completion of follow-up visit (V6)\n- Treatment with any therapy, including endoscopic procedures and/or medication (e.g. liraglutide, bupropion/naltrexone and orlistat), intended for weight management within three months prior to the screening visit\n- Mental incapacity or language barriers that preclude adequate understanding or cooperation or unwillingness to comply with trial requirements\n- Treatment with glucose-lowering agents within three months prior to the screening visit\n- Use of GLP-1RAs, glucagon-like peptide 2 receptor agonists, dipeptidyl peptidase 4 (DPP4) inhibitors, human growth hormone, somatostatin or analogues thereof, within three months prior to screening visit\n- Treatment with antipsychotics known to modulate energy intake three months prior to screening visit\n- Prolonged treatment (>1 week) with anti-inflammatory agents or any PDE4 inhibition within three months prior to the screening visit\n- Glycated haemoglobin (HbA1c) ≥ 48 mmol/mol at the screening visit\n- Compromised kidney function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2) at screening visit\n- Known liver disease (except for MASLD) at screening visit. Elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal\n- History or evidence of hepatitis B virus infection\n- Evidence of hepatitis C virus (HCV) infection. Confirmatory testing for HCV RNA will be conducted for participants who have a positive test result. Participants who have a negative result for HCV RNA will be eligible to participate in the trial\n- Any type of bariatric surgery\n- Known human immunodeficiency virus (HIV) positive or evidence positive for HIV antibodies (HIV-1 or HIV-2)\n- Uncontrolled thyroid disease as per the discretion of the investigators\n- Positive urine human chorionic gonadotropin (hCG) (for fertile women). Regarding fertile men and women: Women who are pregnant, intend to become pregnant, or are breastfeeding will not be included in the study. Sterilised or postmenopausal women (> 12 months amenorrhoea or females ≥ 60 years of age) can be included without the hCG-testing during the trial period. Female of childbearing potential: To exclude pregnancy, urine hCG tests are performed every fourth week after V2 (Week 4, 8, 12, 16 and 20). The following contraceptive methods are considered adequate for study enrolment for females if maintained throughout the study duration: an intrauterine device, hormonal contraception (birth control pills, implant, patch, vaginal ring or injection), a monogamous relationship with a sterilized partner, or sexual abstinence.\n- Previous, current or planned (during the trial period) obesity treatment with surgery or a weight loss device < 12 months prior to the screening visit\n- History of type 1 diabetes or type 2 diabetes\n- History of acute or chronic pancreatitis\n- History and/or family history of medullary carcinoma and/or multiple endocrine neoplasia syndrome\n- 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\n- History of major cardiovascular events three months prior to screening visit, including myocardial infarction, stroke, hospitalisation for angina and transient ischaemic attack"}

Primary endpoints

• {"endpoint_text":"- Percentage change in body weight from week 0 to week 16","definition_or_measurement_approach":"Percentual change from baseline body weight measured at week 0 compared to week 16 (16-week treatment period)."}

Secondary endpoints

• {"endpoint_text":"- Change in body weight in kilograms from week 0 to week 16","definition_or_measurement_approach":"Absolute change in body weight (kg) from baseline (week 0) to week 16."}
• {"endpoint_text":"- Body weight reduction ≥ 3% at week 16","definition_or_measurement_approach":"Proportion of participants achieving ≥3% weight reduction at week 16."}
• {"endpoint_text":"- Body weight reduction ≥ 5% at week 16","definition_or_measurement_approach":"Proportion of participants achieving ≥5% weight reduction at week 16."}
• {"endpoint_text":"- Body weight reduction ≥ 10% at week 16","definition_or_measurement_approach":"Proportion of participants achieving ≥10% weight reduction at week 16."}
• {"endpoint_text":"- change in high sensitivity CRP","definition_or_measurement_approach":"Change in high-sensitivity C-reactive protein concentration (timeframe not further specified; listed among secondary endpoints)."}
• {"endpoint_text":"- change in IL-6","definition_or_measurement_approach":"Change in interleukin-6 concentration (timeframe not further specified)."}
• {"endpoint_text":"- Change in TNF-alfa","definition_or_measurement_approach":"Change in tumor necrosis factor-alpha concentration (timeframe not further specified)."}
• {"endpoint_text":"- Body weight reduction ≥ 15% at week 16","definition_or_measurement_approach":"Proportion of participants achieving ≥15% weight reduction at week 16."}
• {"endpoint_text":"- Change in BMI (kg/m2) from week 0 to 16","definition_or_measurement_approach":"Change in body mass index from baseline to week 16."}
• {"endpoint_text":"- Change in waist-hip ratio from week 0","definition_or_measurement_approach":"Change in waist-to-hip ratio from baseline (week 0); timeframe implied to week 16."}
• {"endpoint_text":"- Change in waist circumference (cm) from week 0 to 16","definition_or_measurement_approach":"Change in waist circumference (cm) from baseline to week 16."}
• {"endpoint_text":"- Change in systolic and diastolic blood pressure (mmHg)","definition_or_measurement_approach":"Change in systolic and diastolic blood pressure; timeframe not further specified (listed among secondary endpoints to week 16)."}
• {"endpoint_text":"- Change in heart rate (beats per minute)","definition_or_measurement_approach":"Change in heart rate (bpm); timeframe not further specified."}
• {"endpoint_text":"- Change in body composition (fat-free mass, total fat mass, visceral fat mass rating and bone mass) as measured by bioimpedance","definition_or_measurement_approach":"Change in body composition parameters measured by bioimpedance; timeframe implied baseline to week 16."}
• {"endpoint_text":"- Change in fasting serum/plasma concentrations of inflammatory biomarkers","definition_or_measurement_approach":"Change in fasting serum/plasma inflammatory biomarker concentrations; timeframe not further specified (listed among secondary endpoints)."}

Denmark

Earliest CTIS Part Ii Submission Date

19-01-2025

Latest Decision Or Authorization Date

21-01-2025

Processing Time Days

2

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Gentofte Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"Sponsor duties (code 1) as listed in third-party entry","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"","full_name":"UNION pharmaceutical","duties_or_roles":"Source of monetary support","organisation_type":""}