Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is an approved and well-established therapy for type 2 diabetes mellitus (T2DM), providing both robust glycemic control and weight reduction. Semaglutide Depot, is a long-acting formulation of semaglutide, designed for once every four weeks administration, intended to reduce treatment burden, and improve adherence supporting sustained glycemic control over time.

This Phase I/Ila dose escalation study design to evaluate the safety, tolerability, pharmacokinetics and efficacy of Semaglutide Depot in adults with T2DM.

Study Title:

A Prospective, Multicenter, Open-Label, Dose Escalation Phase I/Ila Study to Assess the Safety, Tolerability, and Efficacy of Semaglutide Depot in Subjects with Type 2 Diabetes Mellitus

Background:

Type 2 diabetes mellitus (T2DM) is a chronic condition in which the body cannot properly use insulin, leading to elevated blood glucose levels. It is often associated with overweight or obesity and can lead to serious complications if not well controlled.

Semaglutide, is a GLP 1 receptor agonist, that helps lower blood glucose by increasing insulin secretion, reducing glucagon (a hormone that raises blood glucose), slowing gastric emptying, and reducing appetite. In addition to improving glycemic control, it also supports weight loss and has demonstrated cardiovascular benefits. Semaglutide is already approved in several formulations (examples: Ozempic® for type 2 diabetes and Wegovy® for weight management), but these require once-weekly injections.

Semaglutide Depot (SG Depot) is a new, long-acting formulation developed by Mapi Pharma Ltd. It is designed to be injected once every 4 weeks (once monthly), which may make treatment easier and improve adherence for people with diabetes.

Study Design:

• Type: Phase I/Ila, open label, dose escalation study, prospective study
• Sponsor: Mapi Pharma Ltd., Ness Ziona, Israel
• Sites: Tel Aviv, Israel
• Participants: Up to 24 adults with type 2 diabetes
• Groups: Participants will be divided into 4 sequential dose cohorts: 2 mg, 4 mg, 6 mg and 8 mg
• Dose escalation: will be allowed only after review of safety data

Inclusion Criteria:

1. Adults aged 18-64 years with T2DM, BMI 25-35 kg/m2
2. On stable Semaglutide 1 mg weekly and for at least 3 months
3. HbA1c <8%, eGFR≥60 ml/minute
4. For women: either non-childbearing potential or agreement to use acceptable contraception

Exclusion Criteria:

1. Participation in another investigational drug clinical study within 3 months
2. History of cardiovascular or cerebrovascular disease
3. Neuropathy or retinopathy or macular edema necessitating medical treatment
4. Type 1 diabetes
5. Unstable weight (> 5% change in the last 3 months)
6. Current use of insulin and /or sulfonylureas and/or glinides
7. Known contraindications to Semaglutide (per FDA-approved Semaglutide label)
8. Recent immunosuppressive therapy (within 90 days) or chemotherapy for malignancy within 5 years
9. Moderate or severe hepatic impairment, (ALT or AST> 2 x upper limit of normal (ULN)
10. Severe hypertriglyceridemia (triglycerides >500 mg/dl)
11. Pregnant or breast feeding
12. Any condition that may increase risk or interfere with study participation (per Investigator judgement)