Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with T2DM (Type 2 Diabetes Mellitus) inadequately controlled with diet and exercise. Secondary Objectives: * To demonstrate the superiority of once-weekly injection of efpeglenatide in comparison to placebo on glycemic control * To demonstrate the superiority of once-weekly injection of efpeglenatide in comparison to placebo on body weight * To evaluate the safety of once-weekly injection of efpeglenatide
Detailed description
Study duration per participant is approximately 65 weeks, including a 3-week screening period, 30 weeks core treatment period, 26 weeks extension treatment period, and 6 weeks safety follow up.
Interventions
Pharmaceutical form: solution for injection Route of administration: subcutaneous
DRUGplacebo
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Sponsors
Sanofi
Hanmi Pharmaceutical Company Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be at least 18 years of age at the time of signing the informed consent. * Participants with T2DM, and treated with diet and exercise. * Hemoglobin A1c between 7.0% and 10.0% (inclusive) measured by the central laboratory at Screening.
Exclusion criteria
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease within 6 months prior to Screening or history of surgery affecting gastric emptying. * 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. * Personal or family history of Medullary Thyroidian Cancer (MTC) or genetic conditions that predisposes to MTC (eg multiple endocrine neoplasia syndromes). * Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months of screening) or planned: intravitreal injections or laser or vitrectomy surgery. * Body weight change of ≥5 kg within the last 3 months prior to Screening. * Systolic blood pressure \>180 mmHg and/or diastolic blood pressure \>100 mmHg at Randomization. * End-stage renal disease as defined by estimated glomerular filtration rate (eGFR , by Modification of Diet in Renal Disease \[MDRD\]) of \<15 mL/min/1.73 m2. * Laboratory findings at the Screening Visit: * Alanine aminotransferase (ALT ) or aspartate aminotransferase (AST ) \>3 times the upper limit of the normal (ULN ) or total bilirubin \>1.5 times the ULN (except in case of documented Gilbert's syndrome). * Amylase and/or lipase: \>3 times the ULN laboratory range. * Calcitonin ≥5.9 pmol/L (20 pg/mL). * Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to Screening, or planned during study period. * History of drug or alcohol abuse within 6 months prior to the time of Screening. * Pregnant (demonstrated by serum pregnancy test at Screening) or breast-feeding women. * Women of childbearing potential not willing to use highly effective method(s) of birth control during the study period and for at least 5 weeks after the last dose of study intervention. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycated Hemoglobin (HbA1c) (%) | Baseline to Week 30 | Change from Baseline to Week 30 in HbA1c |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | Baseline to Week 30 | Change from Baseline to Week 30 in FPG |
| HbA1c <7% | Week 30 | Number of participants with HbA1c \<7.0% at Week 30 |
| Change in Body Weight at Week 30 | Baseline to Week 30 | Change from Baseline to Week 30 in body weight |
| Change in HbA1c (%) | Baseline to Week 56 | Change from Baseline to Week 56 in HbA1c |
| Hypoglycemic Participants | Baseline to Week 56 | Number of participants with at least 1 hypoglycemic event during treatment period |
| Hypoglycemic Events | Baseline to Week 56 | Number of hypoglycemic events |
| Treatment Emergent Adverse Events (TEAEs) | Baseline to Week 56 | Number of participants with TEAEs |
| Change in Body Weight at Week 56 | Baseline to Week 56 | Change from Baseline to Week 56 in body weight |
Countries
Germany, Poland, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo (Prefilled syringe) administered once weekly for 56 weeks
placebo: Pharmaceutical form: solution for injection
Route of administration: subcutaneous | 102 |
| Efpeglenatide 2 mg Efpeglenatide low dose (Prefilled syringe) administered once weekly for 56 weeks
efpeglenatide (SAR439977): Pharmaceutical form: solution for injection
Route of administration: subcutaneous | 100 |
| Efpeglenatide 4 mg Efpeglenatide middle dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)
efpeglenatide (SAR439977): Pharmaceutical form: solution for injection
Route of administration: subcutaneous | 101 |
| Efpeglenatide 6 mg Efpeglenatide high dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)
efpeglenatide (SAR439977): Pharmaceutical form: solution for injection
Route of administration: subcutaneous | 103 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 26-week Treatment Extension Period | Adverse Event | 1 | 0 | 0 | 1 |
| 26-week Treatment Extension Period | Other: Not related to COVID-19 | 0 | 0 | 1 | 1 |
| 26-week Treatment Extension Period | Protocol Violation | 2 | 0 | 0 | 0 |
| 26-week Treatment Extension Period | Withdrawal by Subject | 2 | 3 | 3 | 12 |
| 30-week Core Treatment Period | Adverse Event | 0 | 4 | 2 | 3 |
| 30-week Core Treatment Period | Other: Not related to COVID-19 | 2 | 2 | 2 | 0 |
| 30-week Core Treatment Period | Protocol Violation | 1 | 1 | 1 | 0 |
| 30-week Core Treatment Period | Withdrawal by Subject | 19 | 12 | 19 | 19 |
Baseline characteristics
| Characteristic | Total | Placebo | Efpeglenatide 2 mg | Efpeglenatide 4 mg | Efpeglenatide 6 mg |
|---|---|---|---|---|---|
| Age, Customized <50 | 94 Participants | 22 Participants | 21 Participants | 30 Participants | 21 Participants |
| Age, Customized ≥50 and <65 | 177 Participants | 43 Participants | 46 Participants | 44 Participants | 44 Participants |
| Age, Customized ≥65 and <75 | 105 Participants | 26 Participants | 28 Participants | 20 Participants | 31 Participants |
| Age, Customized ≥75 | 30 Participants | 11 Participants | 5 Participants | 7 Participants | 7 Participants |
| Baseline BMI | 34.2 kg/m² STANDARD_DEVIATION 6.8 | 34.8 kg/m² STANDARD_DEVIATION 7.1 | 34.4 kg/m² STANDARD_DEVIATION 6.4 | 33.8 kg/m² STANDARD_DEVIATION 6.6 | 33.8 kg/m² STANDARD_DEVIATION 6.9 |
| Baseline BMI category <30 | 112 Participants | 28 Participants | 28 Participants | 28 Participants | 28 Participants |
| Baseline BMI category ≥30 and <40 | 223 Participants | 52 Participants | 53 Participants | 58 Participants | 60 Participants |
| Baseline BMI category ≥40 | 70 Participants | 22 Participants | 19 Participants | 15 Participants | 14 Participants |
| Baseline BMI category Unknown | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity : Hispanic or Latino | 86 Participants | 20 Participants | 20 Participants | 25 Participants | 21 Participants |
| Race/Ethnicity, Customized Ethnicity : Not Hispanic or Latino | 320 Participants | 82 Participants | 80 Participants | 76 Participants | 82 Participants |
| Race/Ethnicity, Customized Race : Asian | 5 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 37 Participants | 10 Participants | 6 Participants | 13 Participants | 8 Participants |
| Race/Ethnicity, Customized Race : Multiple | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race : Other | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race : White | 361 Participants | 90 Participants | 93 Participants | 86 Participants | 92 Participants |
| Region of Enrollment Europe | 184 participants | 48 participants | 47 participants | 44 participants | 45 participants |
| Region of Enrollment North America | 222 participants | 54 participants | 53 participants | 57 participants | 58 participants |
| Screening HbA1c | 8.05 % STANDARD_DEVIATION 0.87 | 7.98 % STANDARD_DEVIATION 0.85 | 8.03 % STANDARD_DEVIATION 0.75 | 8.14 % STANDARD_DEVIATION 0.93 | 8.07 % STANDARD_DEVIATION 0.91 |
| Sex: Female, Male Female | 187 Participants | 51 Participants | 45 Participants | 49 Participants | 42 Participants |
| Sex: Female, Male Male | 219 Participants | 51 Participants | 55 Participants | 52 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 102 | 0 / 103 | 1 / 99 |
| other Total, other adverse events | 70 / 102 | 69 / 102 | 73 / 103 | 77 / 99 |
| serious Total, serious adverse events | 9 / 102 | 11 / 102 | 6 / 103 | 6 / 99 |
Outcome results
Primary
Change in Glycated Hemoglobin (HbA1c) (%)
Change from Baseline to Week 30 in HbA1c
Time frame: Baseline to Week 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Glycated Hemoglobin (HbA1c) (%) | -0.46 HbA1c (%) | Standard Deviation 1.16 |
| Efpeglenatide 2 mg | Change in Glycated Hemoglobin (HbA1c) (%) | -1.14 HbA1c (%) | Standard Deviation 0.96 |
| Efpeglenatide 4 mg | Change in Glycated Hemoglobin (HbA1c) (%) | -1.48 HbA1c (%) | Standard Deviation 1.01 |
| Efpeglenatide 6 mg | Change in Glycated Hemoglobin (HbA1c) (%) | -1.59 HbA1c (%) | Standard Deviation 1.04 |
Secondary
Change in Body Weight at Week 30
Change from Baseline to Week 30 in body weight
Time frame: Baseline to Week 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Body Weight at Week 30 | -1.35 kg | Standard Deviation 3.15 |
| Efpeglenatide 2 mg | Change in Body Weight at Week 30 | -1.01 kg | Standard Deviation 3.66 |
| Efpeglenatide 4 mg | Change in Body Weight at Week 30 | -3.34 kg | Standard Deviation 4.19 |
| Efpeglenatide 6 mg | Change in Body Weight at Week 30 | -3.19 kg | Standard Deviation 4.77 |
Secondary
Change in Body Weight at Week 56
Change from Baseline to Week 56 in body weight
Time frame: Baseline to Week 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Body Weight at Week 56 | -1.26 kg | Standard Deviation 4.19 |
| Efpeglenatide 2 mg | Change in Body Weight at Week 56 | -0.94 kg | Standard Deviation 4.96 |
| Efpeglenatide 4 mg | Change in Body Weight at Week 56 | -3.24 kg | Standard Deviation 6.42 |
| Efpeglenatide 6 mg | Change in Body Weight at Week 56 | -1.82 kg | Standard Deviation 5.52 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from Baseline to Week 30 in FPG
Time frame: Baseline to Week 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Fasting Plasma Glucose (FPG) | 8.59 FPG (mmol/L) | Standard Deviation 2.13 |
| Efpeglenatide 2 mg | Change in Fasting Plasma Glucose (FPG) | -0.87 FPG (mmol/L) | Standard Deviation 3.27 |
| Efpeglenatide 4 mg | Change in Fasting Plasma Glucose (FPG) | 6.84 FPG (mmol/L) | Standard Deviation 1.57 |
| Efpeglenatide 6 mg | Change in Fasting Plasma Glucose (FPG) | 6.55 FPG (mmol/L) | Standard Deviation 1.3 |
Secondary
Change in HbA1c (%)
Change from Baseline to Week 56 in HbA1c
Time frame: Baseline to Week 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1c (%) | -0.52 HbA1c (%) | Standard Deviation 1.18 |
| Efpeglenatide 2 mg | Change in HbA1c (%) | -1.18 HbA1c (%) | Standard Deviation 0.79 |
| Efpeglenatide 4 mg | Change in HbA1c (%) | -1.51 HbA1c (%) | Standard Deviation 0.99 |
| Efpeglenatide 6 mg | Change in HbA1c (%) | -1.51 HbA1c (%) | Standard Deviation 0.18 |
Secondary
HbA1c <7%
Number of participants with HbA1c \<7.0% at Week 30
Time frame: Week 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | HbA1c <7% | 26 Participants |
| Efpeglenatide 2 mg | HbA1c <7% | 60 Participants |
| Efpeglenatide 4 mg | HbA1c <7% | 66 Participants |
| Efpeglenatide 6 mg | HbA1c <7% | 76 Participants |
Secondary
Hypoglycemic Events
Number of hypoglycemic events
Time frame: Baseline to Week 56
Population: Safety population: All participants randomly assigned to IMP and who take at least 1 dose of IMP. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Hypoglycemic Events | 2 Number of events |
| Efpeglenatide 2 mg | Hypoglycemic Events | 10 Number of events |
| Efpeglenatide 4 mg | Hypoglycemic Events | 14 Number of events |
| Efpeglenatide 6 mg | Hypoglycemic Events | 14 Number of events |
Secondary
Hypoglycemic Participants
Number of participants with at least 1 hypoglycemic event during treatment period
Time frame: Baseline to Week 56
Population: Safety population: All participants randomly assigned to IMP and who take at least 1 dose of IMP. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Hypoglycemic Participants | 2 Participants |
| Efpeglenatide 2 mg | Hypoglycemic Participants | 10 Participants |
| Efpeglenatide 4 mg | Hypoglycemic Participants | 14 Participants |
| Efpeglenatide 6 mg | Hypoglycemic Participants | 14 Participants |
Secondary
Treatment Emergent Adverse Events (TEAEs)
Number of participants with TEAEs
Time frame: Baseline to Week 56
Population: Safety population: All participants randomly assigned to IMP and who take at least 1 dose of IMP. Participants were analyzed according to the treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Treatment Emergent Adverse Events (TEAEs) | 79 Number of Treatment Emergent AEs |
| Efpeglenatide 2 mg | Treatment Emergent Adverse Events (TEAEs) | 80 Number of Treatment Emergent AEs |
| Efpeglenatide 4 mg | Treatment Emergent Adverse Events (TEAEs) | 79 Number of Treatment Emergent AEs |
| Efpeglenatide 6 mg | Treatment Emergent Adverse Events (TEAEs) | 83 Number of Treatment Emergent AEs |