None listed
Conditions
Interventions
Efpeglenatide Type of group
Dosage formulation Sterile, non pyrogenic, clear, colorless
solution in a 1 mL disposable PFS in
the formulation buffer (containing citric
acid monohydrate, L-methionine,
polysorbate 20, D-mannitol, sodium
hydroxide and water for injection).
Unit dose strength(s)/Dosage level(s) 2, 4 and 6 mg/ 0.5 mL (at 4, 8 and
12 mg/mL concentrations,
respectively)
Route of administration SC Injection
Dosing instructions The injection interval of the IMP is once weekly on the sam
Dosage formulation
Sterile, non pyrogenic, clear, colorless
solution in a 1 mL disposable PFS in
the formulation buffer (containing citric
acid monohydrate, L-methionine,
polysorbate 20, D-mannitol, sodium
hydroxide and water for injection).
Not applicable
SC Injection
Dosing instructions The injection interval of the IMP is once weekly on the same week day (eg, each
Monday) at any time of the day. Injections should be administered SC to the
abdomen. Within this
Sponsors
Sanofi Aventis Recherche & Development,
Eligibility
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age I 01. Participant must be ≥18 years of age at the time of signing the informed consent. Type of participant and disease characteristics I 02. Participants with T2DM and HbA1c >7% I 03. Participants who meet at least one of the 8 CVD criteria in Table 3 (Review Protocol Section 5.1) OR male participants who are ≥50 years of age or female participants who are ≥55 years of age and have an eGFR ≥25 and <60 mL/min and have at least one of the 6 CV risk factors listed in Table 4 (Review Protocol Section 5.1) Sex I 04. Male or Female a) Male participants: A male participant must agree to use contraception as detailed in Appendix 4 (Section 10.4) of this protocol during the intervention period and for at least 5 weeks after the last dose of study intervention and refrain from donating sperm during this period. b) Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 4 [Section 10.4]) of this protocol, not breastfeeding, and at least one of the following conditions applies: - Not a WOCBP as defined in Appendix 4 (Section 10.4) of this protocol OR - A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 (Section 10.4) of this protocol during the intervention period and for at least 5 weeks after the last dose of study intervention. Informed Consent I 05. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1.2) of this protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
Exclusion criteria: Medical conditions E 01. Clinically relevant history of GI disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and uncontrolled gastroesophageal reflux disease within 6 months prior to screening E 02. History of pancreatitis (unless pancreatitis was related to gallstone and cholecystectomy has been performed) and pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, and pancreatectomy E 03. Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predisposes to MTC (eg, multiple endocrine neoplasia syndromes) E 04. Estimated glomerular filtration rate 180 mmHg and/or DBP >100 mmHg at randomization E 06. Hospitalization for hypertensive emergency within 3 months prior to randomization E 07. Planned coronary revascularization procedures, electrophysiologic device implantation, cardiac mechanical support implantation or other cardiac surgery E 08. History of solid organ transplant E 09. Hypersensitivity to any of the study treatments or any components thereof E 10. No documented ophthalmologic exam with fundoscopy within 6 months prior to screening (or within 3 months in patients with severe non proliferative diabetic retinopathy [NPDR]/ proliferative diabetic retinopathy [PDR]/Diabetic Macular Edema [DME]) E 11. Retinopathy or maculopathy with one of the following treatments, either recent (3 months prior to randomization) or planned during the study: intravitreal injections or laser or vitrectomy surgery E 12. Patients with short life expectancy making implementation of the protocol or interpretation of the study results difficult in the opinion of the investigator including severe anemia, congestive heart failure (New York Heart Association [NYHA] III/IV), respiratory, hepatic, neurological, psychiatric, active malignant tumor or other major systemic disease E 13. History of drug or alcohol abuse within 6 months prior to the time of screening Prior/concomitant therapy E 14. Treated with any GLP-1 RA product (eg, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide) within 3 months prior to screening E 15. Use of any DPP4 inhibitor within 12 weeks prior to screening E 16. Diabetic treatment has not been stable in the 12 weeks prior to screening, in the opinion of the investigator E 17. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for more than 10 consecutive days within 3 months prior to Screening Visit or for more than 10 consecutive days between Screening and randomization Prior/concurrent clinical study experience E 18. Exposure to any investigational drugs in the last 4 weeks or 5 half-lives, whichever is longer, prior to screening E 19. Current enrollment in any other clinical study involving an investigational study treatment E 20. Participation in any previous efpeglenatide/HM11260C clinical trial within 3 months prior to screening E 21. Participant is the Investigator or any Subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol Diagnos
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The time to the first occurrence of the primary composite CV endpoint event (CV death, non-fatal MI, or non-fatal stroke) will be analyzed using Cox proportional hazards model with treatment (efpeglenatide 4 mg, efpeglenatide 6 mg, placebo), region and randomization strata of current or potential future use of a SGLT2 inhibitor (Current use, Potential future use, Neither current nor potential future use) as the covariates. Participants who receive either 4 mg or 6 mg of efpeglenatide will be combined as one efpeglenatide treatment group when making comparisons using appropriate contrast for the purposes of the primary analysis. The hazard ratio between pooled efpeglenatide and placebo will be estimated along with the associated two-sided 95%CI. Measure:Time to the first occurrence of any of the following clinical events, positively adjudicated by the CEC: • CV death • Non-fatal MI • Non-fatal stroke Timepoints:Baseline to approximately 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:The two secondary endpoints will be analyzed using the same Cox proportional hazards model as used for the analysis of primary endpoint. The Cox model will include treatment (efpeglenatide 4mg, efpeglenatide 6 mg, placebo), region, and randomization strata of current or potential future use of a SGLT2 inhibitor (Current use, Potential future use, Neither current nor potential future use) as the covariates. The hazard ratio between pooled efpeglenatide and placebo will be estimated along with the associated two-sided 95%CI. Measure:Time to the first occurrence of any of the following clinical events, positively adjudicated by the CEC: • CV death • Non-fatal MI • Non-fatal stroke • Coronary revascularization • Hospitalization for unstable angina Time to the first occurrence of any of the following clinical events: • New onset or progression to macro albuminuria (>300 mg/g) accompanied by a UACR value increase of ≥30% from Baseline • Sustained ≥40% decrease in eGFR from Baseline (for ≥30 days) • Chronic dialysis (for ≥90 days) • Renal transplant, • Sustained eGFR <15 mL/min/1.73 m2 (for ≥30 days) Timepoints:Baseline to approximately 36 months | — |
Countries
Argentina, Bulgaria, Canada, Chile, Denmark, Estonia, Finland, Germany, Hungary, India, Italy, Korea South, Kyrgystan, Latovia, Lithuania, Mexico, Norway, Peru, Poland, Romania, Serbia, Slovakia, South Africa
Contacts
Public ContactShellah Albites
SANOFI AVENTIS DEL PERU S.A.
Outcome results
None listed