Clinical trial NCT05413369: iGlarLixi vs IDegAsp in Chinese Participants After OAD(s)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-06-10
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a parallel-group treatment, Phase 3, randomized, 2-arm study that assessed the efficacy and safety of iGlarLixi to IDegAsp in Chinese T2DM participants insufficiently controlled with oral antidiabetic drug(s).

Study details included:

* 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 were 14 visits that included 7 phone calls and 7 on-site visits in total during screening and treatment periods. There was 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

Detailed description: 27 weeks

Eligibility criteria: Inclusion Criteria:

* Participant had at least 18 of age inclusive, at the time of signing the informed consent.
* Participants who were diagnosed with T2DM for at least 1 year before the screening visit
* Participants who were 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 were 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 agreed to use contraception during the study duration
* Participants were capable of giving signed informed consent as described in Appendix 1 of the protocol which included compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

* Participant who had 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 withdrawn consent at randomization or were lost to follow up at randomization visit.

The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 24: Non-Inferiority Analysis
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change in HbA1c From Baseline to Week 24: Superiority Analysis
timeFrame: Baseline, Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Reaching HbA1c <7% at Week 24
timeFrame: Week 24
measure: Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24
timeFrame: Week 24
measure: Percentage of Participants Reaching HbA1c <7% With no Body Weight Gain at Week 24 and no Hypoglycemia During 24-Week Treatment Period
timeFrame: Baseline up to Week 24
measure: Change in Fasting Plasma Glucose From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Change in Average 7-Point Self-Monitored Plasma Glucose (SMPG) Profile From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Reaching HbA1c <7% at Week 24 With no Hypoglycemia During 24-Week Treatment Period
timeFrame: Baseline up to Week 24
measure: Percentage of Participants Reaching HbA1c <7% at Week 24 With no Clinically Relevant Hypoglycemia During 24-Week Treatment Period
timeFrame: Baseline up to Week 24
measure: Total Daily Insulin Dose at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Required Rescue Therapy During the 24-Week Treatment Period
timeFrame: Baseline up to Week 24
measure: Change in Fasting C-Peptide From Baseline to Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With Any Hypoglycemia Event During On-Treatment Period
timeFrame: From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days)
measure: Hypoglycemic Event Rate During the On-Treatment Period
timeFrame: From first dose of study drug up to 1 day after the last administration of study drug (maximum treatment exposure: 192 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events Of Special Interest (AESIs) and TEAEs Leading to Treatment Discontinuation
timeFrame: From signature of the informed consent form up to the final visit regardless of seriousness or relationship to study drug (maximum treatment exposure: 192 days)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Vital Signs
timeFrame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematology
timeFrame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Clinical Chemistry
timeFrame: From first dose of study drug up to 3 days after last administration of study drug (maximum treatment exposure: 192 days)
Other outcomes:
Locations:
city: Baotou
country: China
facility: Investigational Site Number : 1560008
city: Beijing
country: China
facility: Investigational Site Number : 1560001
city: Beijing
country: China
facility: Investigational Site Number : 1560027
city: Beijing
country: China
facility: Investigational Site Number : 1560019
city: Cangzhou
country: China
facility: Investigational Site Number : 1560023
city: Changchun
country: China
facility: Investigational Site Number : 1560059
city: Changchun
country: China
facility: Investigational Site Number : 1560046
city: Changde
country: China
facility: Investigational Site Number : 1560052
city: Changsha
country: China
facility: Investigational Site Number : 1560011
city: Chengdu
country: China
facility: Investigational Site Number : 1560054
city: Chengdu
country: China
facility: Investigational Site Number : 1560024
city: Chenzhou
country: China
facility: Investigational Site Number : 1560004
city: Chongqing
country: China
facility: Investigational Site Number : 1560044
city: Dalian
country: China
facility: Investigational Site Number : 1560053
city: Foshan
country: China
facility: Investigational Site Number : 1560030
city: Guangzhou
country: China
facility: Investigational Site Number : 1560043
city: Guangzhou
country: China
facility: Investigational Site Number : 1560029
city: Handan
country: China
facility: Investigational Site Number : 1560021
city: Hangzhou
country: China
facility: Investigational Site Number : 1560010
city: Harbin
country: China
facility: Investigational Site Number : 1560045
city: Harbin
country: China
facility: Investigational Site Number : 1560025
city: Huai'an
country: China
facility: Investigational Site Number : 1560056
city: Huanggang
country: China
facility: Investigational Site Number : 1560035
city: Huangshi
country: China
facility: Investigational Site Number : 1560055
city: Huhehaote
country: China
facility: Investigational Site Number : 1560038
city: Huizhou
country: China
facility: Investigational Site Number : 1560022
city: Huzhou
country: China
facility: Investigational Site Number : 1560051
city: Jinan
country: China
facility: Investigational Site Number : 1560040
city: Jinan
country: China
facility: Investigational Site Number : 1560014
city: Jingzhou
country: China
facility: Investigational Site Number : 1560058
city: Kaifeng
country: China
facility: Investigational Site Number : 1560041
city: Lanzhou
country: China
facility: Investigational Site Number : 1560039
city: Lianyungang
country: China
facility: Investigational Site Number : 1560060
city: Luoyang
country: China
facility: Investigational Site Number : 1560031
city: Nanjing
country: China
facility: Investigational Site Number : 1560028
city: Nanjing
country: China
facility: Investigational Site Number : 1560017
city: Nanjing
country: China
facility: Investigational Site Number : 1560018
city: Nantong
country: China
facility: Investigational Site Number : 1560057
city: Pingxiang
country: China
facility: Investigational Site Number : 1560037
city: Qingdao
country: China
facility: Investigational Site Number : 1560048
city: Qinhuangdao
country: China
facility: Investigational Site Number : 1560012
city: Shanghai
country: China
facility: Investigational Site Number : 1560003
city: Shanghai
country: China
facility: Investigational Site Number : 1560020
city: Shanghai
country: China
facility: Investigational Site Number : 1560007
city: Shanghai
country: China
facility: Investigational Site Number : 1560006
city: Shenyang
country: China
facility: Investigational Site Number : 1560009
city: Suzhou
country: China
facility: Investigational Site Number : 1560050
city: Tianjin
country: China
facility: Investigational Site Number : 1560016
city: Tianjin
country: China
facility: Investigational Site Number : 1560013
city: Tonghua
country: China
facility: Investigational Site Number : 1560047
city: Xingtai
country: China
facility: Investigational Site Number : 1560042
city: Xuzhou
country: China
facility: Investigational Site Number : 1560015
city: Yueyang
country: China
facility: Investigational Site Number : 1560033
city: Yueyang
country: China
facility: Investigational Site Number : 1560032
city: Yuncheng
country: China
facility: Investigational Site Number : 1560026
city: Zhengzhou
country: China
facility: Investigational Site Number : 1560049
city: Zhenjiang
country: China
facility: Investigational Site Number : 1560034
city: Zhongshan
country: China
facility: Investigational Site Number : 1560036
city: Zhuzhou
country: China
facility: Investigational Site Number : 1560005
city: Zigong
country: China
facility: Investigational Site Number : 1560002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: