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

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

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®.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: GP40071; Drug: NovoRapid® Penfill®

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangel'sk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Hospital
  • Kazan, Russian Federation, 420073
    • Kazan Endocrinology Dispensary
  • Krasnoyarsk, Russian Federation, 660022
    • Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky
  • Moscow, Russian Federation, 117036
    • Endocrinology Research Centre (Moscow)
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation, 194354
    • City Diagnostic Center № 1
  • Saint Petersburg, Russian Federation, 194358
    • City Polyclinic № 117
  • Saint Petersburg, Russian Federation, 195197
    • EosMed
  • Saint Petersburg, Russian Federation, 196084
    • Institute of Medical Research
  • Saint Petersburg, Russian Federation, 197341
    • Almazov National Medical Research Centre
  • Saint Petersburg, Russian Federation, 199106
    • Pokrovskaya Municipal Hospital
  • Saint Petersburg, Russian Federation, 190013
    • Polyclinic Сomplex
  • Samara, Russian Federation, 443067
    • Diabetes Center
  • Saratov, Russian Federation, 410030
    • Clinical City Hospital № 9

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GP40071; Subcutaneous (SC), before meals intake, up to Week 26	Drug: GP40071; 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.; Other Names: Insulin aspart
Active Comparator: NovoRapid® Penfill®; Subcutaneous (SC), before meals intake, up to Week 26	Drug: NovoRapid® Penfill®; 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.; Other Names: Insulin aspart

What is the study measuring?

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
Body Mass Index	Change in BMI from baseline	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
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
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

Collaborators and Investigators

• Sponsor: Geropharm

Publications and helpful links

General Publications

• Karonova TL, Mayorov AY, Magruk MA, Zyangirova ST, Grigoryeva IV, Khmelnitski OK, Myshkovets A, Parfenova TM, Mosikian AA, Drai RV. Safety and efficacy of GP40071 compared with originator insulin aspart (NovoRapid(R) Penfill(R)) in Type 1 diabetes mellitus. J Comp Eff Res. 2021 Jun;10(9):763-775. doi: 10.2217/cer-2020-0208. Epub 2021 Apr 30.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): January 21, 2020
• Study Completion (Actual): January 21, 2020

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; Insulin aspart; Aspart
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: GP40071-P4-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No