Weight management with orismilast alone or in combination with s.c. semaglutide (WELOSITI)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gentofte Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2025-01-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

UNION pharmaceutical

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

This randomised placebo-controlled study will investigate the efficacy of orismilast administered orally twice daily (BID) separately or combined with open-label once weekly s.c. administered semaglutide in individuals with obesity during a 16-week treatment period.
The primary aim is to evaluate the effects of 30 mg orismilast BID with- or without semaglutide 1.0 mg s.c. once weekly on percentual change from baseline in body weight.

Conditions and MedDRA coding

obesity

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age 18-75
2. BMI ≥ 30 kg/m²
3. History of at least one attempt to lose body weight

Exclusion criteria 32

1. A self-reported change in body weight ≥ 5% within the last three months prior to the screening visit
2. 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
3. Any type of bariatric surgery
4. Previous, current or planned (during the trial period) obesity treatment with surgery or a weight loss device < 12 months prior to the screening visit
5. History of type 1 diabetes or type 2 diabetes
6. History of acute or chronic pancreatitis
7. History and/or family history of medullary carcinoma and/or multiple endocrine neoplasia syndrome
8. 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
9. History of major cardiovascular events three months prior to screening visit, including myocardial infarction, stroke, hospitalisation for angina and transient ischaemic attack
10. History of major depressive disorder within 2 years of screening
11. Unstable severe psychiatric disorder (e.g. bipolar disorder or schizophrenia)
12. Suicidal behaviour three months prior to screening visit
13. Any prior suicidal attempt
14. Class IV heart failure, according to the New York Heart Association
15. Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardise the participant’s safety during the trial
16. Alcohol/drug abuse as per discretion of the investigators
17. Known or suspected hypersensitivity to orismilast, semaglutide or related products
18. Administration of any investigational drug within three months prior to the screening visit
19. Simultaneous participation in any other clinical intervention trial until completion of follow-up visit (V6)
20. Mental incapacity or language barriers that preclude adequate understanding or cooperation or unwillingness to comply with trial requirements
21. Treatment with glucose-lowering agents within three months prior to the screening visit
22. 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
23. Treatment with antipsychotics known to modulate energy intake three months prior to screening visit
24. Prolonged treatment (>1 week) with anti-inflammatory agents or any PDE4 inhibition within three months prior to the screening visit
25. Glycated haemoglobin (HbA1c) ≥ 48 mmol/mol at the screening visit
26. Compromised kidney function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2) at screening visit
27. Known liver disease (except for MASLD) at screening visit. Elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal
28. History or evidence of hepatitis B virus infection
29. 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
30. Known human immunodeficiency virus (HIV) positive or evidence positive for HIV antibodies (HIV-1 or HIV-2)
31. Uncontrolled thyroid disease as per the discretion of the investigators
32. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage change in body weight from week 0 to week 16

Secondary endpoints 15

1. Change in body weight in kilograms from week 0 to week 16
2. Body weight reduction ≥ 3% at week 16
3. Body weight reduction ≥ 5% at week 16
4. Body weight reduction ≥ 10% at week 16
5. change in high sensitivity CRP
6. change in IL-6
7. Change in TNF-alfa
8. Body weight reduction ≥ 15% at week 16
9. Change in BMI (kg/m2) from week 0 to 16
10. Change in waist-hip ratio from week 0
11. Change in waist circumference (cm) from week 0 to 16
12. Change in systolic and diastolic blood pressure (mmHg)
13. Change in heart rate (beats per minute)
14. Change in body composition (fat-free mass, total fat mass, visceral fat mass rating and bone mass) as measured by bioimpedance
15. Change in fasting serum/plasma concentrations of inflammatory biomarkers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gentofte Hospital

Sponsor organisation

Gentofte Hospital

Address

Gentofte Hospitalsvej 1

City

Hellerup

Postcode

2900

Country

Denmark

Scientific contact point

Organisation

Gentofte Hospital

Contact name

Center for Clinical Metabolic Research

Public contact point

Organisation

Gentofte Hospital

Contact name

Center for Clinical Metabolic Research

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications