Gan & Lee Insulin Glargine Target Type (1) Evaluating Research (GLITTER 1)

AN OPEN-LABEL, RANDOMIZED, MULTICENTER, PHASE 3 STUDY TO COMPARE THE IMMUNOGENICITY, EFFICACY, AND SAFETY OF GAN & LEE PHARMACEUTICALS INSULIN GLARGINE INJECTION TO LANTUS® IN ADULT SUBJECTS WITH TYPE 1 DIABETES MELLITUS

Primary Objective:

•To evaluate equivalence of Gan & Lee Insulin Glargine Injection and Lantus® in terms of immunogenicity

Secondary Objective:

Immunogenicity:

• To evaluate the percentage of subjects with negative anti-insulin antibodies (AIAs) at baseline who develop confirmed positive AIA up to Week 26, the percentage of baseline in AIA titers between treatment groups, the percentage of subjects with confirmed positive AIA who develop any anti-insulin neutralizing antibodies up to visit Week 26, and percentage of subjects who develop confirmed positive AIA up to visit Week 26 of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®.

Safety:

•To evaluate the safety of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®.

Efficacy:

•To evaluate the efficacy of Gan & Lee Insulin Glargine Injection in comparison with that of Lantus®.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Biological: Gan & Lee Insulin Glargine Injection; Biological: Lantus®

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Holešov, Czechia, 769 01
    • Diahaza s.r.o.
  • Hradec Králové, Czechia, 503 41
    • StefaMed
  • Krnov, Czechia, 794 01
    • Diabetologie MUDr. Tomáš Edelsberger
  • Olomouc, Czechia, 779 00
    • PreventaMed
  • Ostrava, Czechia, 709 00
    • Genom s.r.o
  • Jihocesky KRAJ
    • České Budějovice, Jihocesky KRAJ, Czechia, 370 01
      • Diabetologie České Budějovice s.r.o
  • Severoceský KRAJ
    • Ústí Nad Labem, Severoceský KRAJ, Czechia, 401 13
      • Krajská zdravotní, a.s., Masarykova nemocnice v Ústí nad Labem
• Germany
  • Bayern
    • Aschaffenburg, Bayern, Germany, 63739
      • Studienzentrum Aschaffenburg
  • Brandenburg
    • Falkensee, Brandenburg, Germany, 14612
      • Diabetes-falkensee.de
  • Nordrhein-westfalen
    • Dortmund, Nordrhein-westfalen, Germany, 44137
      • Gemeinschaftspraxis Diabeteszentrum Dortmund
    • Duisburg, Nordrhein-westfalen, Germany, 47051
      • Diabetes Schwerpunktpraxis, Gemeinschaftspraxis Alain Barakat und Helene Willems
  • Sachsen
    • Pirna, Sachsen, Germany, 01796
      • Diabetologische Schwerpunktpraxis Pirna
  • Schleswig-holstein
    • Oldenburg, Schleswig-holstein, Germany, 23758
      • RED-Institut GmbH
• Hungary
  • Budapest, Hungary, 1023
    • Betegapolo-Irgalmasrend Budai Irgalmasrendi Kórház, Diabetológiai Ambulancia
  • Budapest, Hungary, 1036
    • Synexus Magyarorszag
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem II. Sz. Belgyogyaszati Klinika
  • Bacs-kiskun
    • Baja, Bacs-kiskun, Hungary, 6500
      • Lausmed Egeszsegugyi es Szolgaltato Kft.
  • Borsod-abauj-zemplen
    • Miskolc, Borsod-abauj-zemplen, Hungary, 3529
      • CRU Hungary Egészségügyi és Szolgáltató Kft.
  • Heves
    • Eger, Heves, Hungary, 3300
      • Markhot Ferenc Oktatokorhaz Es Rendelointezet
  • Zala
    • Zalaegerszeg, Zala, Hungary, H-8900
      • Zala County Hospital
• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-109
      • KO-MED Centra Kliniczne Lublin - Królewska
  • Malopolskie
    • Kraków, Malopolskie, Poland, 30-510
      • PRATIA MCM Kraków
    • Kraków, Malopolskie, Poland, 31-261
      • NZOZ Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne "Diab-Endo-Met"
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-546
      • Centrum Badan Klinicznych PI-House
    • Gdansk, Pomorskie, Poland, 80-858
      • Niepubliczny Zaklad Opieki Zdrowotnej Gdanska Poradnia Cukrzycowa
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 61-655
      • Praktyka Lekarska Ewa Krzyzagorska
• Spain
  • La Coruna, Spain, 15006
    • Complejo Hospitalario Universitario La Coruna
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Sevilla, Spain, 41003
    • Nuevas tecnologías en Diabetes y Endocrinología
  • Sevilla, Spain, 41014
    • Hospital Universitario Nuestra Señora de Valme
  • Valencia, Spain, 46014
    • Consorci Hospital General Universitari de València
  • Gerona
    • Girona, Gerona, Spain, 17007
      • Hospital Universitari de Girona Doctor Josep Trueta
  • LA Coruna
    • Ferrol, LA Coruna, Spain, 15405
      • Complejo Hospitalario Universitario de Ferrol
  • Malaga
    • Málaga, Malaga, Spain, 29006
      • Centro de Especialidades San Jose Obrero. Hospital Universitario Virgen de la Victoria
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Fresno, California, United States, 93720
      • Valley Research
    • Newport Beach, California, United States, 92663-3303
      • The Rose Salter Medical Research Foundation
    • Northridge, California, United States, 91324
      • California Medical Research Association
    • Tarzana, California, United States, 91356
      • Metabolic Institute of America
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • CMR of Greater New Haven, LLC
  • Florida
    • Bradenton, Florida, United States, 34201
      • Meridien Research
    • Fort Lauderdale, Florida, United States, 33312
      • The Center for Diabetes and Endocrine Care
    • Homestead, Florida, United States, 33032
      • Homestead Associates in Research
    • Maitland, Florida, United States, 32751
      • Central Florida Endocrine and Diabetes Consultants - Maitland
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33155
      • Biotech Pharmaceutical Group, LLC
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research, LLC
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Blue Ridge, Georgia, United States, 30513
      • River Birch Research Alliance, Llc
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta
    • Marietta, Georgia, United States, 30060
      • Sestron Clinical Research
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research - Idaho
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hospital of Cook County
    • Crystal Lake, Illinois, United States, 60012
      • Midwest CRC
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503-1473
      • Kentucky Diabetes Endocrinology Center
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center, Inc.
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East - Greenville
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Columbus, Ohio, United States, 43213-6523
      • Aventiv Research, Inc.
    • Columbus, Ohio, United States, 43201
      • Endocrinology Reserach Associates, Inc.
    • Dayton, Ohio, United States, 45419
      • PriMed Clinical Research
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes & Endocrine Consultants
    • Chattanooga, Tennessee, United States, 37421
      • ClinSearch - Clinical Research Specialists
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development
  • Texas
    • Austin, Texas, United States, 78731-4309
      • Texas Diabetes & Endocrinology - Central Austin
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology - South Austin
    • Dallas, Texas, United States, 75231
      • Research Institute of Dallas
    • Round Rock, Texas, United States, 78681
      • Texas Diabetes & Endocrinology - Round Rock
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio
  • Utah
    • Murray, Utah, United States, 84123
      • Radiant Research
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
  • Virginia
    • Burke, Virginia, United States, 22105
      • Burke Internal Medicine & Research
  • Washington
    • Federal Way, Washington, United States, 98003
      • Stonesifer Clinical Research
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center, Inc.
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research & Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or nonpregnant, nonlactating female subjects between the ages of 18 and 75 years, inclusive.
2. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and all applicable regulations, before initiating any study-related procedures.
3. Ability to understand and fully comply with all study procedures and restrictions.
4. Subjects with a confirmed diagnosis of type 1 diabetes mellitus who have been on an approved basal and bolus insulin regimen for at least 6 months (the type or brand of insulin should not have changed in the 6 months before screening).
5. HbA1c ≤ 11.0%.
6. BMI ≥ 19 kg/m2 and ≤ 35 kg/m2.
7. Adherence to a prudent diet and exercise regimen recommended by the medical provider, and willingness to maintain these consistently for the duration of the study.
8. Concomitant medications are allowed, provided that no significant dosing changes are anticipated during the study (see the exclusion criteria below for specific prohibited concomitant medications); for concomitant thyroid medications, subjects must have been on a stable dosage for 90 days before screening.

Exclusion Criteria:

1. Participation in another clinical study or use of any study drug within 30 days before screening.
2. Previous use of a biosimilar insulin, either basal or bolus.
3. Diabetic ketoacidosis within a year before screening.
4. Brittle type 1 diabetes mellitus within the year before screening (e.g., multiple hospitalizations related to diabetes mellitus and/or severe hypoglycemia for which the subject required 3rd party assistance).
5. Any severe, delayed sequela of diabetes mellitus, e.g., worsening end-stage renal disease, advanced coronary artery disease, or myocardial infarction within the year before screening, or autonomic peristaltic problems, e.g., gastroparesis.
6. Anticipated change in insulin used during the study (change in dosage is allowed, but change in type or brand of insulin will result in the subject being withdrawn from the study).
7. Inadequately controlled thyroid disease, defined as a TSH or free T4 value > the upper limit of normal.
8. BMI < 19 kg/m2 or > 35 kg/m2.
9. Any clinically significant (in the opinion of the Investigator) hematology or chemistry test results at screening, including any liver function test > 3x the upper limit of normal (subjects with elevated bilirubin due to Gilbert syndrome are eligible to participate).
10. Documented history of anti-insulin antibodies.
11. Treatment with glucocorticosteroids, immunosuppressants, or cytostatic agents within 60 days before screening (newly-prescribed or high-dose corticosteroids are prohibited; chronically administered oral, inhaled, topical, or intra-articular corticosteroids at a stable dosage are allowed if no increase in dose is anticipated during the study; See Appendix 3 [Section 17.3] for a list of allowed and prohibited medications).
12. Current use of medication intended to cause weight loss or weight gain.
13. Alcohol or substance use disorder within the 2 years before screening.
14. Any previous or anticipated treatment with interferons.
15. Any history of malignant disease within 5 years before screening, except for adequately treated basal cell carcinoma.
16. Severe concomitant physical or psychiatric diseases or conditions
17. A history of a positive test result for HIV, hepatitis B, or hepatitis C; any subject who has a positive test result during the study may continue at the discretion of the Investigator.
18. Any history of pancreatitis or pancreatectomy.
19. Any diagnosis or condition that requires the subject to undergo procedures that could decrease antibodies in plasma or that would require treatment with immunosuppressant agents.
20. Any condition e.g., splenectomy, autoimmune disease, or rheumatologic disease, that could affect immunologic responses, could indicate an altered immune system, or could require treatment with a prohibited medication.
21. Any unresolved infection or a history of active infection within 30 days before screening other than mild or viral illness (as judged by the Investigator).
22. Any other disease or condition that in the opinion of the Investigator could confound the study results or limit the subject's ability to participate in the study or comply with follow-up procedures; or any other factor that would indicate a significant risk of loss to follow up.
23. Intolerance or history of hypersensitivity to insulin glargine or any excipient of IP.
24. Inability or unwillingness to wear the CGM sensor as required for the study, or to comply with the concomitant medication requirements in the FreeStyle Libre Pro Indications and Important Safety Information, during the CGM periods.

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: Gan & Lee Insulin Glargine Injection; Gan & Lee Insulin Glargine Injection for subcutaneous injection, 100 U/mL, in the integrated, disposable 3.0-mL pre-filled Gan & Lee injector pen. Subjects randomized to the Gan & Lee Insulin Glargine Injection group will participate in the study for 26 weeks.	Biological: Gan & Lee Insulin Glargine Injection; Route of administration: subcutaneous injection
Active Comparator: Lantus®; Lantus® (insulin glargine injection) solution for subcutaneous injection, 100 U/mL, in the SoloStar® 3.0 mL pre-filled insulin pen. Subjects randomized to the Lantus® group will participate for 26 weeks.	Biological: Lantus®; Route of administration: subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	The percentage of subjects in each treatment group who develop treatment induced AIA, defined as treatment-emergent AIA development or important (at least 4-fold) increase in titers and up to visit Week 26.	Up to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in HbA1c from baseline at visit Week 26 to be measured and reported	The change in HbA1c from baseline at visit Week 26.	Up to Week 26
Immunogenicity - Percentage of subjects in each treatment group with negative AIA at baseline who develop confirmed positive AIA after baseline	The percentage of subjects in each treatment group with negative AIA at baseline who develop confirmed positive AIA after baseline and up to visit Week 26.	Up to Week 26
Immunogenicity - Percentage of subjects in each treatment group with confirmed positive AIA at baseline and at least a 4-fold increase in titers after baseline	The percentage of subjects in each treatment group with confirmed positive AIA at baseline and at least a 4-fold increase in titers after baseline and up to visit Week 26.	Up to Week 26
Immunogenicity - Mean change from baseline in each treatment group in AIA titers after baseline	The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26.	Up to Week 26
Immunogenicity - Percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26 who develop any anti-insulin neutralizing antibodies after baseline	The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26 who develop any anti-insulin neutralizing antibodies after baseline and up to visit Week 26.	Up to Week 26
Immunogenicity - Percentage of subjects in each treatment group with confirmed positive AIA after baseline	The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.	Up to Week 26
Safety - The incidence and severity of all treatment-emergent adverse events	The incidence and severity of all treatment-emergent adverse events and the following subgroups: Hypoglycemia, which will be fully documented prospectively in the Hypoglycemic Events Record. Serious adverse events, including fatal events. Adverse events leading to termination of the study treatment and/or early withdrawal from the study. IP-related adverse events. Injection site reactions. The incidence of clinically significant laboratory abnormalities. The incidence of clinically significant abnormalities in ECG and vital signs.	Up to Week 26
Efficacy - The number and percentage of subjects who achieve an FBG test result ≤ 6.0 mmol/L (≤ 108.0 mg/dL)	The number and percentage of subjects who achieve an FBG test result of ≤ 6.0 mmol/L (≤ 108.0 mg/dL) at visit Week 26.	Up to Week 26
Efficacy - The number and percentage of subjects who achieve a HbA1c of < 7.0%	The number and percentage of subjects who achieve a HbA1c of < 7.0% at visit Week 26.	Up to Week 26

Collaborators and Investigators

• Sponsor: Gan and Lee Pharmaceuticals, USA
• Investigators: Study Director: Jia Lu, MD, PhD, Gan & Lee Pharmaceuticals, USA; Principal Investigator: Elena A. Christofides, MD,FACE, Endocrinology Research Associates, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2017
• Primary Completion (Actual): August 19, 2019
• Study Completion (Actual): August 19, 2019

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Diabetes Mellitus; Basal; Diabetes Type 1; Glargine; T1DM; Type 1; Insulin Dependent Diabetes
• 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
• Other Study ID Numbers: GL-GLAT1-3001

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