iGlarLixi vs IDegAsp in Chinese Participants After OAD(s)

Study Overview
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Brief Summary
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This is a parallel-group treatment, Phase 3, randomized, 2-arm study to assess the efficacy and safety of iGlarLixi to IDegAsp in Chinese T2DM participants insufficiently controlled with oral antidiabetic drug(s). Study details include: Study duration per participant: approximately up to 27 weeks Treatment duration: 24 weeks Visit frequency: after screening (an on-site visit), on-site or phone call visit every 1 week from randomization till Week 4, every 2 weeks till week 12 and then every 3 weeks till Week 24 (End of Treatment). There will be 14 visits including 7 phone call and 7 on-site visits in total during screening and treatment periods. There will be a safety follow-up by a phone call visit (End of Study) in 3 days after the last dose of the treatment. Health measurement/Observation: change in HbA1c as the primary endpoint. Intervention name: iGlarLixi and IDegAsp Participant sex: male and female Participant age range: adults at least 18 years of age Condition/disease: Type 2 diabetes mellitus Study hypothesis: Compared to IDegAsp, iGlarLixi will demonstrate a similar therapeutic effect on glycemic control assessed by change in HbA1c from baseline to Week 24 in the study participants.

Detailed Description
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27 weeks

Official Title
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A Randomized, 24 Weeks, Active-controlled, Open-label, 2-arm Multicenter Study Comparing the Efficacy and Safety of iGlarLixi to IDegAsp in Chinese Type 2 Diabetes Mellitus Participants Insufficiently Controlled With Oral Antidiabetic Drug(s)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glargine/Lixisenatide
* Drug: IDegAsp
* Drug: Metformin
* Drug: SGLT2 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be at least 18 of age inclusive, at the time of signing the informed consent. Participants who are diagnosed with T2DM for at least 1 year before the screening visit Participants who are treated for at least 3 months prior to the screening visit with a stable dose of metformin (at least 1000 mg/day or the maximum tolerated dose) alone or in combination with a second oral antidiabetic treatment that can be a sulfonylurea (SU), a glinide, an alpha-glucosidase inhibitor (alpha-GI), a dipeptidyl-peptidase-4 (DPP-4) inhibitor or a sodium-glucose co-transporter 2 (SGLT-2) inhibitor HbA1c at screening visit: between 7.5% and 11%, both inclusive, for participants previously treated with metformin alone or + SGLT-2 inhibitor, or between 7.0% and 10%, both inclusive, for participants previously treated with metformin + a second oral antidiabetic treatment other than SGLT-2 inhibitor. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. Body mass index (BMI) <40 kg/m² at screening Male or female, including females of childbearing potential who agree to use contraception during the study duration Capable of giving signed informed consent as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria: Participant who has a severe renal function impairment with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² Pregnant or breast-feeding woman. Woman of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to be tested for pregnancy Conditions/situations such as: Participant with short life expectancy. Participant with conditions/concomitant diseases making him/her not evaluable for the primary efficacy endpoint (eg, hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to screening). Participant with conditions/concomitant diseases precluding his/her safe participation in this study (eg, active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require laser treatment within the study period). Uncooperative or any condition that could make the participant potentially non-compliant to the study procedures (e.g., participant unable or unwilling to do self-injections or blood glucose monitoring using the Sponsor-provided blood glucometer at home). Previous treatment with insulin (except for short-term treatment ≤14 days due to intercurrent illness at the discretion of the Investigator) within 1 year prior to screening. Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within 3 months prior to screening. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1 week or more within 3 months prior to screening. Use of weight loss drugs within 3 months prior to screening. History of discontinuation of a previous treatment with GLP-1 RAs due to safety/tolerability reasons or lack of efficacy. Use of any investigational drug other than specified in this protocol within 1 month or 5 half-lives, whichever is longer, prior to screening. Laboratory findings tested at the screening visit: Amylase and/or lipase >3 times the upper limit of normal (ULN) laboratory range. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 ULN. Total bilirubin >1.5 ULN (except in case of Gilbert's syndrome). Calcitonin ≥20 pg/mL (5.9 pmol/L). Hemoglobin <10.5 g/dL and/or neutrophils <1500/mm^3 and/or platelets <100 000/mm^3. Positive urine pregnancy test in female of childbearing potential. Contraindication to metformin and/or SGLT-2 inhibitor use, for those who were taking it prior to the study, according to local labeling, warning/precaution of use (when appropriate) as displayed in the respective National regulation Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6) Any specific situation during study implementation/course that may raise ethics considerations Sensitivity to any of the study interventions (insulin or, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study Participants who withdraw consent at randomization or are loss to follow up at randomization visit. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iGlarLixi<br>iGlarLixi (insulin glargine/lixisenatide) will be self-administered subcutaneously once daily in the morning in the hour (0 to 60 minutes) before the first meal on top of metformin ± SGLT-2 inhibitor for 24 weeks | Drug: Insulin glargine/Lixisenatide<br>* solution, by subcutaneous injection<br>Drug: Metformin<br>* Tablet, orally<br>Drug: SGLT2 inhibitor<br>* Tablet, orally<br>|
| Active Comparator: IDegAsp<br>IDegAsp will be self-administered subcutaneously once daily prior to the largest meal of the day according to the locally approved label on top of metformin ± SGLT-2 inhibitor for 24 weeks | Drug: IDegAsp<br>* solution, by subcutaneous injection<br>Drug: Metformin<br>* Tablet, orally<br>Drug: SGLT2 inhibitor<br>* Tablet, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline to Week 24 |  | from baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c |  | from baseline to Week 24 | 
| Change in body weight |  | from baseline to Week 24 | 
| Proportion of participants to reach HbA1c<7% |  | At week 24 | 
| Proportion of participants reaching HbA1c targets <7% without body weight gain |  | At week 24 | 
| Proportion of participants reaching HbA1c < 7% with no body weight gain and no hypoglycemia (defined as ADA Level 1, 2 or 3) |  | At week 24 | 
| Change in Fasting plasma glucose |  | from baseline to week 24 | 
| Change in 7-point self-monitored plasma glucose (SMPG) profile |  | from baseline to week 24 | 
| Proportion of participants reaching HbA1c target <7% with no hypoglycemia (defined as ADA level 1, 2 or 3) |  | At week 24 | 
| Proportions of participants reaching HbA1c target < 7% with no clinically relevant hypoglycaemia (defined as ADA level 2 or 3) |  | At week 24 | 
| Total insulin dose in each group |  | At week 24 | 
| Percentage of participants requiring rescue therapy |  | During the 24-week treatment period | 
| Incidence and Event rates of hypoglycemia (Any, ADA classification level 1, 2, and 3) |  | from baseline to Week 24 | 
| Adverse events (AEs), SAEs, adverse events of special interest (AESIs), and AEs leading to treatment discontinuation, vital signs and safety laboratory values |  | from baseline to Week 24 | 
| Change in fasting C-peptide |  | from baseline to Week 24 |