A Study of Insulin Efsitora Alfa (LY3209590) Compared With Insulin Degludec in Participants With Type 1 Diabetes Treated With Multiple Daily Injection Therapy

Phase 3

Completed

Conditions: Type 1 Diabetes
Diabetes

Interventions: Drug: Insulin Efsitora Alfa
Drug: Insulin Degludec

Registration Number: NCT05463744

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to measure the safety and efficacy of insulin efsitora alfa (LY3209590) compared with insulin degludec in participants with type 1 diabetes treated with multiple daily injection therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 692

Inclusion Criteria

Have a clinical diagnosis of type 1 diabetes for at least 1 year prior to screening
Have received treatment with basal-bolus insulin analog multiple daily injection therapy according to the local product label for at least 90 days prior to screening
Have an HbA1c value of 7.0% to 10.0%, inclusive, as determined by the central laboratory at screening.
Have a body mass index of ≤35 kilogram/square meter (kg/m²)

Exclusion Criteria

Have a diagnosis of type 2 diabetes, latent autoimmune diabetes, or specific types of diabetes other than type 1 diabetes
Have a history of more than 1 episode of severe hypoglycemia, within the 6 months prior to screening.
Have a history of more than 1 episode of diabetic ketoacidosis or hyperosmolar state or coma requiring hospitalization within the 6 months prior to screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Insulin Efsitora Alfa	Insulin Efsitora Alfa	Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 units per milliliter (U/mL) Insulin Lispro) received 500 U/mL of insulin efsitora alfa administered once weekly (QW) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.
Insulin Degludec	Insulin Degludec	Participants who were treated with prestudy basal insulin and prandial insulin therapy (100 U/mL Insulin Lispro) received 100 U/mL of Insulin Degludec administered once daily (QD) for 52 weeks as subcutaneous injection, followed by a 5-week safety follow-up.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Noninferiority Analysis]	Baseline, Week 26	HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined using Analysis of Covariance (ANCOVA) model with treatment + country + CGM use prior to study entry \[yes/no\]+ carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Superiority Analysis]	Baseline, Week 26	HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] From Week 23 to Week 26	Week 23 to Week 26	Percentage of time in glucose range between 70 and 180 milligram per deciliter (mg/dL) \[3.9 and 10.0 millimole per liter (mmol/L)\], measured by continued glucose monitoring (CGM) from week 23 to week 26 inclusive over a 24-Hour Period. The time component of the time-in-range statistic was calculated using the display time recorded by the CGM device. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 23-26 were imputed by return-to-baseline multiple imputations approach
Nocturnal Hypoglycemia Event Rate	Baseline up to Week 52	The event rate of participant-reported clinically significant nocturnal hypoglycemia (defined as blood glucose level \<54 mg/dL (3.0 mmol/L) or severe hypoglycemia and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 52. Group mean was reported and determined by Negative binomial model using Number of episodes = Baseline hypoglycemia rate + HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Change From Baseline in HbA1c at Week 52 [Noninferiority Analysis]	Baseline, Week 52	HbA1c is the glycosylated fraction of hemoglobin A. It is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was determined using ANCOVA model with treatment + country + CGM use prior to study entry \[yes/no\]+ carbohydrate counting for prandial insulin\[yes/no\] + baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach
Change From Baseline in Fasting Blood Glucose	Baseline, Week 26, and Week 52	Change from baseline in fasting blood glucose measured by self-monitoring blood glucose (SMBG). LS mean was determined using ANCOVA model with treatment, country, CGM use prior to study entry \[yes/no\], carbohydrate counting for prandial insulin dosing \[yes/no\]) and baseline value of the dependent variable as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data were imputed by return-to-baseline multiple imputations approach.
Glucose Variability	Week 23 to Week 26 and Week 49 to Week 52	Glucose variability measured as coefficient of variation (CV) for blood glucose during the CGM session over a 24-hour period, between Week 23 to Week 26 and Week 49 to Week 52 was reported. LS mean was determined using mixed model repeated measures (MMRM) model with BASELINE + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Hemoglobin A1c Stratum at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Unstructured variance-covariance structure was used.
Percentage of Time in the Blood Glucose Range Between 70 and 180 mg/dL [3.9 and 10.0 mmol/L] From Week 49 to Week 52	Week 49 to Week 52	Percentage of time spent within the blood glucose range of 70 to 180 mg/dL \[3.9 to 10.0 mmol/L\], as measured during the CGM session over a 24-hour period, from Week 49 to Week 52. LS mean was determined using ANCOVA model with treatment, country, CGM use prior to study entry \[yes/no\], carbohydrate counting for prandial insulin dosing \[yes/no\]) and Hemoglobin A1c Stratum at baseline and baseline value of the dependent variable as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data were imputed by return-to-baseline multiple imputations approach.
Bolus Insulin Dose	Week 26 and Week 52	The insulin dose was recorded daily or weekly in an electronic diary. The average daily bolus insulin dose at Week 26 and Week 52 was reported. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Total Insulin Dose	Week 26 and Week 52	The average weekly total insulin dose is the sum of the average weekly basal and bolus doses. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Basal Insulin Dose to Total Insulin Dose Ratio	Week 26 and Week 52	The basal/total insulin dose ratio is the average weekly basal dose divided by the average weekly total dose. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Hypoglycemia Event Rate	Baseline up to Week 52	Rate of Composite Level 2 and 3 Hypoglycemia Events were reported. Hypoglycemia with glucose \<54 mg/dL (Level 2) or Severe Hypoglycemia confirmed by the investigator to be an event that required assistance for treatment (Level 3) was reported. A severe hypoglycemic event is characterized by altered mental or physical status requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions for the treatment of hypoglycemia. Group mean was reported and determined by Negative binomial model using Number of episodes = Baseline hypoglycemia rate + HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Change From Baseline in Body Weight	Baseline, Week 26, and Week 52	Change from baseline in body weight was reported. LS Mean was determined by MMRM model using Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Percentage of Time in Hypoglycemia Range With Blood Glucose <54 mg/dL (3.0 mmol/L)	Week 23 to Week 26 and Week 49 to Week 52	Percentage of time spent in the hypoglycemia range with blood glucose \< 54 mg/dL (3.0 mmol/L), as measured during the CGM session over a 24-hour period from week 23 to week 26 and week 49 to week 52 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (Type III sum of squares). as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at week 23-26 and week 49-52 were imputed by return-to-baseline multiple imputations approach.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) at Week 26	Week 26	The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which measure Treatment Satisfaction, dealing with: 1. satisfaction with current treatment; 2. convenience of the treatment; 3. flexibility; 4. satisfaction with own understanding of participant's diabetes; 5. how likely to recommend their present treatment; and 6. how satisfied to continue with their present treatment. Each item is rated on a 7-point Likert scale (which ranges from -3 (much less satisfied) to +3 (much more satisfied). The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) at Week 52	Week 52	The DTSQc score is used to assess relative change in participant satisfaction from baseline. The questionnaire consists of 8 items, 6 of which measure Treatment Satisfaction, dealing with: 1. satisfaction with current treatment; 2. convenience of the treatment; 3. flexibility; 4. satisfaction with own understanding of participant's diabetes; 5. how likely to recommend their present treatment; and 6. how satisfied to continue with their present treatment. Each item is rated on a 7-point Likert scale (which ranges from -3 (much less satisfied) to +3 (much more satisfied). The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment.
Change From Baseline in Short Form-36 Version 2 (SF-36 v2) Acute Form (Physical-Component and Mental-Component) Scores	Baseline, Week 26, and Week 52	The SF-36v2 is a participant-reported measure designed to assess health status using 36 items across 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The 8 health domains are aggregated into two summary scores known as the physical component summary (PCS) score and the mental component summary (MCS) score. Scoring of each domain and both summary scores are norm based and presented in the form of T-scores, with a mean of 50 and a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores. LS Mean was determined by MMRM model with Baseline + Country + Carbohydrate counting for Prandial Dose + Prior CGM use + Hemoglobin A1c Stratum at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). as variables. Unstructured variance-covariance structure was used.
Basal Insulin Dose	Week 26 and Week 52	The insulin dose was recorded daily or weekly in an electronic diary. The average weekly basal insulin dose at Week 26 and Week 52 was reported. LS mean was determined using MMRM model with BASELINE + Hemoglobin A1c Stratum at Baseline + Country + Prior CGM use + Carbohydrate counting for Prandial Dose + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-covariance structure was set as compound symmetry.
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) From Week 23 to Week 26	Week 23 to Week 26	Percentage of time spent in the hyperglycemia range with blood glucose greater than (\>) 180 mg/dL (10.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 23 to Week 26 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at week 23-week 26 were imputed by return-to-baseline multiple imputations approach.
Percentage of Time in Hyperglycemia Range With Blood Glucose >180 mg/dL (10.0 mmol/L) From Week 49 to Week 52	Week 49 to Week 52	Percentage of time spent in the hyperglycemia range with blood glucose greater than (\>) 180 mg/dL (10.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 49 to Week 52 was reported. LS Mean was determined by ANCOVA model using treatment + country + CGM use prior to study entry \[yes/no\] + carbohydrate counting for prandial insulin dosing \[yes/no\] + Hemoglobin A1c Stratum at Baseline and baseline value of the dependent variable (Type III sum of squares) as variables. Missing data at Baseline were imputed with multiple imputation with assumption of missing at random. Missing data at week 49-week 52 were imputed by return-to-baseline multiple imputations approach.

Trial Locations

Locations (82): John Muir Physician Network Research Center
🇺🇸
Concord, California, United States
Valley Research
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Fresno, California, United States
Catalina Research Institute, LLC
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Montclair, California, United States
Sansum Diabetes Research Institute
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Santa Barbara, California, United States
University Clinical Investigators, Inc.
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Tustin, California, United States
University of Colorado Anschutz Medical Campus
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Aurora, Colorado, United States
Northeast Research Institute (NERI)
🇺🇸
Fleming Island, Florida, United States
Jellinger and Lerman, MD PA dba The Center for Diabetes and Endocrine Care
🇺🇸
Fort Lauderdale, Florida, United States
Suncoast Clinical Research, Inc.
🇺🇸
New Port Richey, Florida, United States
Hanson Clinical Research Center
🇺🇸
Port Charlotte, Florida, United States
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John Muir Physician Network Research Center
🇺🇸Concord, California, United States