Efficacy and Safety of GP40071 Compared to NovoRapid® Penfill® in Type 1 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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This trial is a multi-center, open-label, randomized, parallel group trial in adult patients with T1DM comparing the efficacy and safety of GP40071 (insulin aspart, GEROPHARM) with that of NovoRapid®.

Official Title
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An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of GP40071 (OOO GEROPHARM, Russia) Compared to NovoRapid® Penfill® (Novo Nordisk A/S, Denmark) in Type 1 Diabetes Mellitus Patients

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: GP40071
* Drug: NovoRapid® Penfill®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written consent Diabetes mellitus type 1 for at least 12 months prior to screening History of basis-bolus (multiple dose injection (MDI)) therapy in stable doses at least 30 days Glycated hemoglobin (HbA1c) level of 7.1 to 12.0 % at screening (both values inclusive) Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive) Subject is able and willing to comply with the requirements of the study protocol Exclusion Criteria: Contraindication to the use of insulin aspart Insulin resistance over 1.5 U/kg insulin pro day Change INN of insulin for 6 months prior to randomisation History of treatment any biosimilar insulin for 6 months prior to randomisation (excl. GEROPHARM's insulins) History of treatment any experimental drugs or medical devices for 3 months prior to randomisation History of treatment insulin pump for 180 days prior to signed written consent or indication for use insulin pump Presence of severe diabetes complications History of severe hypoglycemia for 6 months prior to screening History of 15 or more episodes mild hypoglycemia for 1 month prior to screening History or presence of uncontrolled diabetes mellitus for 6 months prior to screening History of administration of glucocorticoids (14 days or more) for 1 year prior to screening Administration of any immunosuppressive drugs (Cyclosporine, Methotrexate, Rituximab, etc.) History of vaccination for 6 months prior to randomisation History of autoimmune disease, except vitiligo and controlled autoimmune polyglandular syndrome (APS) types 1-3, except adrenal insufficiency History of unstable angina, myocardial infarction, severe arrhythmia, heart failure III or IV NYHA for 1 year prior to screening History of stroke or TIA for 6 months prior to screening History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions Pregnant and breast-feeding women Acute inflammation disease for 3 weeks prior to screening Deviation of the laboratory results conducted during the screening: Hemoglobin value < 9,0 g/dl; Hematocrit value < 30 %; ALT and AST value > 2 folds as high as maximal normal value; Serum bilirubin value > 1.5 folds as high as maximal normal value History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, etc.) Serious blood loss for 3 months prior to screening (blood donation, surgery procedure, etc.) Incomplete recovery after surgery procedure History of drug, alcohol abuse for 3 years prior to screening Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg), hepatitis C (HCVAb) or syphilis (Treponema pallidum) antibodies at screening History of oncological disease during 5 years prior to screening History of transplantation, except 3 months after corneal transplant History or presence of a medical condition or disease that in the investigator's opinion would embarrass glycemic control and completion of the study Inability follow to protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP40071<br>Subcutaneous (SC), before meals intake, up to Week 26 | Drug: GP40071<br>* GP40071, 100 per milliliters (U/mL) (dose range of 1 unit to 80 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake.<br>* Other names: Insulin aspart;|
| Active Comparator: NovoRapid® Penfill®<br>Subcutaneous (SC), before meals intake, up to Week 26 | Drug: NovoRapid® Penfill®<br>* NovoRapid® Penfill®, 100 per milliliters (U/mL) (dose range of 1 unit to 80 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake.<br>* Other names: Insulin aspart;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Change from baseline in titer of antibodies to human insulin | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin | Change in HbA1c from baseline | 26 weeks | 
| Adverse Events frequency and degree | Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency; Occurrence of local reactions at injection sites; Occurrence allergic reactions | 26 weeks | 
| Fasting Plasma Glucose Level | Change in fasting plasma glucose level from baseline | 26 weeks | 
| Seven-Point Glucose Testing | Change in seven-point glucose testing results from baseline | 26 weeks | 
| Total Insulin Dose | Change in total insulin dose per body weight (U/kg) from baseline | 26 weeks | 
| Body Mass Index | Change in BMI from baseline | 26 weeks | 
| Treatment Satisfaction | Change in treatment satisfaction from baseline. The total score DTSQ (The Diabetes Treatment Satisfaction Questionnaire) (range 0-36). Questions 1, 4, 5, 6, 7 and 8 assesses treatment satisfaction (summed these 6 questions). Questions 2 and 3 assess the burden from hyper- and hypoglycemia. | 26 weeks | 
| Achievement of Glycated Hemoglobin Goals | The frequency of achievement glycated hemoglobin goals | 26 weeks | 
| Achievement of Glycated Hemoglobin < 7% | The frequency of achievement glycated hemoglobin < 7% ( 7% inclusive) | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Insulin aspart, Aspart