Efficacy and Safety of Insulin RinGlar® Compared to Lantus® SoloStar® in Type 1 Diabetes Mellitus Patients

An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of Insulin RinGlar® ("Geropharm", Russia) Compared to Lantus® SoloStar® ("Sanofi-Aventis Deutschland GmbH", Germany) in Type 1 Diabetes Mellitus Patients

The study is designed to approve non-inferior efficacy and safety of Insulin RinGlar® compared to Lantus® SoloStar® in Type 1 Diabetes Mellitus Patients.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Lantus Solostar, 100 Units/mL Subcutaneous Solution; Drug: Insulin RinGlar, 100 Units/mL Subcutaneous Solution

• Study Type: Interventional
• Enrollment (Actual): 180
• 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)
  • Petrozavodsk, Russian Federation, 185000
    • V.A. Baranov Republic Hospital
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University
  • Saint Petersburg, Russian Federation, 194354
    • City Diagnostic Center № 1
  • Saint Petersburg, Russian Federation, 194354
    • City Hospital № 2
  • Saint Petersburg, Russian Federation, 194358
    • City Polyclinic № 117
  • Saint Petersburg, Russian Federation, 195197
    • EosMed
  • 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
  • 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 6.5 to 12.0 % at screening (both values inclusive)
• Body mass index (BMI) of 18.0 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 glargine
• Insulin resistance over 1.5 U/kg insulin pro day
• History of treatment any biosimilar insulin
• History of treatment any experimental drugs or medical devices for 3 months prior to screening
• History of treatment insulin pump for 90 days prior to signed written consent or indication for use insulin pump
• Presence of severe diabetes complications
• History of severe hypoglycemia during 6 months prior to signed written consent
• History of 15 or more episodes mild hypoglycemia during 1 month prior to signed written consent
• History or presence of uncontrolled diabetes mellitus for 6 months prior to screening
• History of administration of glucocorticoids for 1 year prior to screening
• Administration of any immunosupressive drugs (Cyclosporinum, Methotrexatum, etc.)
• History of autoimmune disease, except vitiligo and controlled autoimmune polyglandular syndrome (APS) types 1-3, except adrenal insufficiency
• 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
• History of severe allergic 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 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 drug, alcohol abuse for 3 years prior to screening
• Inability follow to protocol
• History of oncological disease during 5 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 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

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
Active Comparator: Lantus® SoloStar®; Lantus® SoloStar® once a day, individually glucose-level based administered in stable doses, started before enrollement	Drug: Lantus Solostar, 100 Units/mL Subcutaneous Solution; 4 weeks of glucose-level based dose titration, 22 weeks of treatment with stable doses
Experimental: Insulin RinGlar®; Insulin RinGlar® once a day, individually glucose-level based administered in stable doses, started before enrollement	Drug: Insulin RinGlar, 100 Units/mL Subcutaneous Solution; 4 weeks of glucose-level based dose titration, 22 weeks of treatment with stable doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Response	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
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
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 (4+22 weeks)
Seven-Point Glucose Testing	Change in seven-point glucose testing results from baseline	26 weeks
Basal Insulin Dose	Change in basal insulin dose per body weight (U/kg) 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 overall treatment satisfaction (DTSQ score) from baseline	26 weeks

Collaborators and Investigators

• Sponsor: Geropharm
• Investigators: Principal Investigator: Tatyana L Karonova, MD, DSc, Almazov National Medical Research Centre

Publications and helpful links

General Publications

• Karonova TL, Mosikian AA, Mayorov AY, Makarenko IE, Zyangirova ST, Afonkina OA, Belikova TM, Zalevskaya AG, Khokhlov AL, Drai RV. Safety and efficacy of GP40061 compared with originator insulin glargine (Lantus(R)): a randomized open-label clinical trial. J Comp Eff Res. 2020 Mar;9(4):263-273. doi: 10.2217/cer-2019-0136. Epub 2020 Feb 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2018
• Primary Completion (Actual): February 25, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: July 5, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Insulin; Diabetes Mellitus, Type 1; Glargine
• 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 Glargine; Pharmaceutical Solutions
• Other Study ID Numbers: GLARGIN-IM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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