A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003)

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and efficacy of MK-1293 to Lantus™ in participants with T1DM. The primary hypothesis is that after 24 weeks, the mean change in hemoglobin A1c (A1C) from baseline is non-inferior in participants treated with MK-1293 compared with participants treated with Lantus™.

Official Title
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A Phase III Clinical Trial to Study the Safety and Efficacy of MK-1293 Compared to Lantus™ in Subjects With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: MK-1293
* Drug: Lantus™
* Drug: Prandial Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1DM For at least 1 year is currently using or has been using prandial insulin for at least 4 weeks. Participants taking any type of basal insulin should require a total daily dose of >=10 units/day. For participants currently taking pre-mixed insulin, the basal insulin component should be equivalent to a total daily dose of >=10 units/day. is male, or is female who is not of reproductive potential or if of reproductive potential agrees to remain abstinent or use (or have their partner use) an acceptable method of birth control during the study and for 14 days after the last dose of study medication Exclusion Criteria: has had 1 or more severe hypoglycemic episodes associated with hypoglycemic seizure or loss of consciousness within the past 6 months history of ketoacidosis in the last 6 months participant, as assessed by the investigator, is not appropriate for or does not agree to target a fasting glucose of 70-100 mg/dL [3.9 -5.6 mmol/L]. history of intolerance or hypersensitivity to Lantus™ or contraindication to Lantus™ or one of its excipients used a formulation of insulin glargine other than Lantus™ has received injectable incretin-based therapy within the past 8 weeks on a weight loss program and not in the maintenance phase, or has started a weight loss medication within the past 8 weeks has undergone bariatric surgery within the past 12 months is likely to require treatment for 2 or more consecutive weeks or repeated courses of corticosteroids (note: inhaled, nasal, and topical corticosteroids are permitted) has undergone a surgical procedure within the past 4 weeks or has planned major surgery during the study has new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has any following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder has severe peripheral vascular disease has high blood pressure has chronic myopathy, or a progressive neurological or neuromuscular disorder has active nephropathy history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease has human immunodeficiency virus (HIV) has a hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) history of malignancy in the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer history of melanoma, leukemia, lymphoma, or renal cell carcinoma is currently being treated for hyperthyroidism or has been on a stable dose of thyroid hormone replacement therapy for <6 weeks is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence is pregnant or breast-feeding, or is expecting to conceive or donate eggs has donated blood products or has had phlebotomy of >300 mL within the past 8 weeks or intends to donate blood products during the study has poor mental function or works the night shift

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: MK-1293<br>MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L). | Drug: MK-1293<br>* MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Initial dose will be determined based on the participant's previous insulin therapy. Thereafter, the dose will be titrated to the suggested target for fasting fingerstick glucose levels. MK-1293 dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.<br>Drug: Prandial Insulin<br>* Participants will continue their prandial insulin during the study.<br>|
| Active Comparator: Lantus<br>Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of >70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L). | Drug: Lantus™<br>* Lantus™ dosed subcutaneously once daily at bedtime for 52 weeks. Initial dose will be determined based on the participant's previous insulin therapy. Thereafter, the dose will be titrated to the suggested target for fasting fingerstick glucose levels. Lantus™ dosing once daily at times other than bedtime will be permitted for participants with a previously established dosing time.<br>* Other names: Insulin glargine;Drug: Prandial Insulin<br>* Participants will continue their prandial insulin during the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary: Change From Baseline in Hemoglobin A1c (A1C) at Week 24 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 24 A1C minus the Week 0 A1C. | Baseline and Week 24 | 
| Percentage of Participants With Any Confirmed Positive Anti-insulin Antibody (AIA) at Any Time Up Through Week 24 | Percentage of participants with confirmed positive AIA at any time up through Week 24 including baseline. | Up to Week 24 | 
| Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 24 | Percentage of participants who became positive to AIA at or before Week 24, among participants who were AIA negative at baseline. | Up to Week 24 | 
| Change From Baseline in AIA Titer After 24 Weeks of Treatment | This immunogenicity analysis will assess the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 24 weeks of treatment. This change from baseline reflects the Week 24 AIA titer minus the Week 0 AIA titer. | Baseline and Week 24 | 
| Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24 | Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INab) development up through 24 weeks of treatment. | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in A1C at Week 52 | A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. | Baseline and Week 52 | 
| Total Insulin Dose at Week 24 | Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication). | Week 24 | 
| Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 24 | Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication). | Week 24 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 | Blood glucose was measured on a fasting basis (collected after a 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. | Baseline and Week 24 | 
| Percentage of Participants With Confirmed Positive AIA Up Through Week 52 | Percentage of participants with confirmed positive AIA at any time up through Week 52 including baseline. | Up to Week 52 including baseline | 
| Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 52 | Percentage of participants who became positive to AIA at or before Week 52, among participants who were AIA negative at baseline. | Up to Week 52 | 
| Change From Baseline in AIA Titer After 52 Weeks of Treatment | This immunogenicity analysis assessed the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 52 weeks of treatment. This change from baseline reflects the AIA titers at Week 52 minus the AIA titers at Week 0. | Baseline and Week 52 | 
| Total Insulin Dose at Week 52 | Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication). | Week 52 | 
| Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 52 | Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication). | Week 52 | 
| Change From Baseline in FPG at Week 52 | Blood glucose was measured on a fasting basis (collected after a 10-hour fast). This change from baseline reflects the FPG level at Week 52 minus the FPG level at Week 0. | Baseline and Week 52 | 
| Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 52 | Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Thought Week 52. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INAb) development up through 52 weeks of treatment. | Up to Week 52 | 
| Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) at Week 24 | The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning. | Baseline and Week 24 | 
| Change From Baseline in 7-point SMBG at Week 52 | The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning. | Baseline and Week 52 | 
| Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment. | Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 24 weeks of treatment. | 24 weeks | 
| Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment. | Percentage of participants attaining A1C glycemic goals of <7.0% and <6.5% after 52 weeks of treatment. | 52 weeks | 
| Basal Insulin Dose at Week 52 | Basal Insulin Dose at Week 52. | Week 52 | 
| Basal Insulin Dose Per kg of Body Weight at Week 52 | Basal Insulin Dose per kg of Body Weight at Week 52. | Week 52 | 
| Bolus Insulin Dose at Week 52 | Bolus Insulin Dose at Week 52. | Week 52 | 
| Bolus Insulin Dose Per kg of Body Weight at Week 52 | Bolus Insulin Dose per kg of Body Weight at Week 52. | Week 52 | 
| Basal Insulin Dose at Week 24 | Basal Insulin Dose at Week 24. | Week 24 | 
| Basal Insulin Dose Per kg of Body Weight at Week 24 | Basal Insulin Dose per kg of Body Weight at Week 24. | Week 24 | 
| Bolus Insulin Dose at Week 24 | Bolus Insulin Dose at Week 24. | Week 24 | 
| Bolus Insulin Dose Per kg of Body Weight at Week 24 | Bolus Insulin Dose per kg of Body Weight at Week 24. | Week 24 |