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出境医 / 临床实验 / Efficacy and Safety of Insulin RinGlar® Compared to Lantus® SoloStar® in Type 1 Diabetes Mellitus Patients

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

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

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Diabetes Mellitus Drug: Lantus Solostar, 100 Units/mL Subcutaneous Solution Drug: Insulin RinGlar, 100 Units/mL Subcutaneous Solution Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 4, 2018
Actual Primary Completion Date : February 25, 2019
Actual Study Completion Date : May 15, 2019
Arms and Interventions
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

Outcome Measures
Primary Outcome Measures :
  1. Antibody Response [ Time Frame: 26 weeks ]
    Change from baseline in titer of antibodies to human insulin


Secondary Outcome Measures :
  1. Adverse Events frequency and degree [ Time Frame: 26 weeks (4+22 weeks) ]
    Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency; Occurrence of local reactions at injection sites; Occurrence allergic reactions.

  2. Glycated hemoglobin [ Time Frame: 26 weeks ]
    Change in HbA1c from baseline

  3. Fasting Plasma Glucose Level [ Time Frame: 26 weeks ]
    Change in fasting plasma glucose level from baseline

  4. Seven-Point Glucose Testing [ Time Frame: 26 weeks ]
    Change in seven-point glucose testing results from baseline

  5. Basal Insulin Dose [ Time Frame: 26 weeks ]
    Change in basal insulin dose per body weight (U/kg) from baseline

  6. Total Insulin Dose [ Time Frame: 26 weeks ]
    Change in total insulin dose per body weight (U/kg) from baseline

  7. Body Mass Index [ Time Frame: 26 weeks ]
    Change in BMI from baseline

  8. Treatment Satisfaction [ Time Frame: 26 weeks ]
    Change in overall treatment satisfaction (DTSQ score) from baseline

  9. Achievement of Glycated Hemoglobin Goals [ Time Frame: 26 weeks ]
    The frequency of achievement glycated hemoglobin goals

  10. Achievement of Glycated Hemoglobin < 7% [ Time Frame: 26 weeks ]
    The frequency of achievement glycated hemoglobin < 7% ( 7% inclusive)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Locations
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Russian Federation
Arkhangelsk Regional Clinical Hospital
Arkhangel'sk, Russian Federation, 163045
Kazan Endocrinology Dispensary
Kazan, Russian Federation, 420073
Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky
Krasnoyarsk, Russian Federation, 660022
Endocrinology Research Centre (Moscow)
Moscow, Russian Federation, 117036
V.A. Baranov Republic Hospital
Petrozavodsk, Russian Federation, 185000
Rostov State Medical University
Rostov-on-Don, Russian Federation, 344022
Polyclinic Сomplex
Saint Petersburg, Russian Federation, 190013
City Diagnostic Center № 1
Saint Petersburg, Russian Federation, 194354
City Hospital № 2
Saint Petersburg, Russian Federation, 194354
City Polyclinic № 117
Saint Petersburg, Russian Federation, 194358
EosMed
Saint Petersburg, Russian Federation, 195197
Almazov National Medical Research Centre
Saint Petersburg, Russian Federation, 197341
Pokrovskaya Municipal Hospital
Saint Petersburg, Russian Federation, 199106
Clinical City Hospital № 9
Saratov, Russian Federation, 410030
Sponsors and Collaborators
Geropharm
Investigators
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Principal Investigator: Tatyana L Karonova, MD, DSc Almazov National Medical Research Centre
Tracking Information
First Submitted Date  ICMJE July 5, 2019
First Posted Date  ICMJE July 17, 2019
Last Update Posted Date July 17, 2019
Actual Study Start Date  ICMJE July 4, 2018
Actual Primary Completion Date February 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
Antibody Response [ Time Frame: 26 weeks ]
Change from baseline in titer of antibodies to human insulin
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Adverse Events frequency and degree [ Time Frame: 26 weeks (4+22 weeks) ]
    Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency; Occurrence of local reactions at injection sites; Occurrence allergic reactions.
  • Glycated hemoglobin [ Time Frame: 26 weeks ]
    Change in HbA1c from baseline
  • Fasting Plasma Glucose Level [ Time Frame: 26 weeks ]
    Change in fasting plasma glucose level from baseline
  • Seven-Point Glucose Testing [ Time Frame: 26 weeks ]
    Change in seven-point glucose testing results from baseline
  • Basal Insulin Dose [ Time Frame: 26 weeks ]
    Change in basal insulin dose per body weight (U/kg) from baseline
  • Total Insulin Dose [ Time Frame: 26 weeks ]
    Change in total insulin dose per body weight (U/kg) from baseline
  • Body Mass Index [ Time Frame: 26 weeks ]
    Change in BMI from baseline
  • Treatment Satisfaction [ Time Frame: 26 weeks ]
    Change in overall treatment satisfaction (DTSQ score) from baseline
  • Achievement of Glycated Hemoglobin Goals [ Time Frame: 26 weeks ]
    The frequency of achievement glycated hemoglobin goals
  • Achievement of Glycated Hemoglobin < 7% [ Time Frame: 26 weeks ]
    The frequency of achievement glycated hemoglobin < 7% ( 7% inclusive)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Insulin RinGlar® Compared to Lantus® SoloStar® in Type 1 Diabetes Mellitus Patients
Official Title  ICMJE 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
Brief Summary The study is designed to approve non-inferior efficacy and safety of Insulin RinGlar® compared to Lantus® SoloStar® in Type 1 Diabetes Mellitus Patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus
Intervention  ICMJE
  • Drug: Lantus Solostar, 100 Units/mL Subcutaneous Solution
    4 weeks of glucose-level based dose titration, 22 weeks of treatment with stable doses
  • Drug: Insulin RinGlar, 100 Units/mL Subcutaneous Solution
    4 weeks of glucose-level based dose titration, 22 weeks of treatment with stable doses
Study Arms  ICMJE
  • Active Comparator: Lantus® SoloStar®
    Lantus® SoloStar® once a day, individually glucose-level based administered in stable doses, started before enrollement
    Intervention: Drug: Lantus Solostar, 100 Units/mL Subcutaneous Solution
  • Experimental: Insulin RinGlar®
    Insulin RinGlar® once a day, individually glucose-level based administered in stable doses, started before enrollement
    Intervention: Drug: Insulin RinGlar, 100 Units/mL Subcutaneous Solution
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(®)): 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 16, 2019)
180
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 15, 2019
Actual Primary Completion Date February 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04022993
Other Study ID Numbers  ICMJE GLARGIN-IM
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Geropharm
Study Sponsor  ICMJE Geropharm
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tatyana L Karonova, MD, DSc Almazov National Medical Research Centre
PRS Account Geropharm
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP