Gan & Lee Evaluation of New Biosimilar for Type 1 Lispro (GENTL 1)

An Open-label, Randomized, Multicenter, Phase 3 Study to Compare the Immunogenicity, Efficacy, and Safety of Gan & Lee Insulin Lispro Injection to Humalog in Adult Subjects With Type 1 Diabetes Mellitus (T1DM)

Primary Objective:

• To compare the immunogenicity of Gan & Lee Insulin Lispro Injection and EU-authorized Humalog following treatment in adult subjects with T1DM

Secondary Objectives:

• To evaluate the safety of Gan & Lee Insulin Lispro Injection in comparison with that of EU authorized Humalog following treatment in adult subjects with T1DM
• To evaluate the efficacy of Gan & Lee Insulin Lispro Injection in comparison with that of EU authorized Humalog following treatment in adult subjects with T1DM

Study Overview

• Status: Withdrawn
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Biological: Gan & Lee Insulin Lispro Injection; Biological: Humalog

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Holešov, Czechia, 769 01
    • Diahaza s.r.o.
  • Hradec Králové, Czechia, 503 41
    • StefaMed
  • Praha 10, Czechia, 100 00
    • Clintrial
  • Praha 11, Czechia, 149 00
    • Milan Kvapil s.r.o
  • Jihocesky KRAJ
    • České Budějovice, Jihocesky KRAJ, Czechia, 370 01
      • Diabetologie České Budějovice s.r.o
• Germany
  • Dortmund, Germany, 44137
    • Diabeteszentrum DO
  • Duisburg, Germany, 47051
    • Diabetes Schwerpunktpraxis
  • Falkensee, Germany, 14612
    • Diabetes-falkensee.de - Zentrum für klinische Studien
  • Oldenburg, Germany, 23758
    • RED-Institut GmbH
  • Saarlouis, Germany, 66740
    • Diabetologische Praxis
• Hungary
  • Baja, Hungary, 6500
    • Lausmed Egeszsegugyi es Szolgaltato Kft.
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Korhaz Es Rendelointezet
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
  • Budapest, Hungary, 1213
    • Trantor 99 Bt Anyagcsere Centrum
  • Debrecen, Hungary, 4031
    • Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
  • Gyula, Hungary, 5700
    • Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház
  • Nagykanizsa, Hungary, 8801
    • Kanizsai Dorottya Korhaz
  • Szombathely, Hungary, 9700
    • Markusovszky Egyetemi Oktatokorhaz
  • Veszprém, Hungary, 8200
    • Medical-Expert Kutatási - Kísérleti és Szolgáltató Kft
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Szent Rafael Kórház
• Poland
  • Gdansk, Poland, 80-858
    • Niepubliczny Zaklad Opieki Zdrowotnej Gdanska Poradnia Cukrzycowa
  • Gdańsk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House
  • Gdynia, Poland, 81-338
    • Centrum Medyczne Pratia Gdynia
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Kraków, Poland, 30-510
    • Pratia McM Kraków
  • Kraków, Poland, 31-261
    • NZOZ Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne "Diab-Endo-Met"
  • Lublin, Poland, 20 044
    • CenterMed Lublin Sp. z o.o
  • Lublin, Poland, 20-109
    • KO-MED Centra Kliniczne Lublin - Królewska
  • Lublin, Poland, 20-538
    • Bogdan Walko Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Specjalistyczna MEDICA
  • Poznan, Poland, 60-369
    • Centrum Medyczne Grunwald
  • Toruń, Poland, 87-100
    • Nasz Lekarz Przychodnie Medyczne
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie
  • Warszawa, Poland, 01-518
    • AMED Centrum Medyczne
  • Wołomin, Poland, 05-230
    • Centrum Medyczne K2J2
  • Wrocław, Poland, 52-416
    • Centrum Medyczne OPOROW
  • Wrocław, Poland, 50-127
    • Regionalna Poradnia Diabetologiczna
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8025
    • Hospital de la Santa Creu i de Sant Pau
  • Ferrol, Spain, 15405
    • Complejo Hospitalario Universitario de Ferrol
  • La Coruña, Spain, 15006
    • Complejo Hospitalario Universitario La Coruña (Gerencia de Gestión Integrada de A Coruña)
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Málaga, Spain, 29006
    • Hospital Universitario Virgen de la Victoria
  • Santa Coloma de Gramenet, Spain, 8923
    • Fundacio Hospital de L'Esperit Sant
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41014
    • Hospital Universitario Virgen de Valme
  • Sevilla, Spain, 41003
    • Nuevas tecnologías en Diabetes y Endocrinología
• United States
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center
    • Fresno, California, United States, 93720
      • Valley Research
    • Los Angeles, California, United States, 90057
      • Angel City Research, Inc.
    • Northridge, California, United States, 91324
      • California Medical Research Association
    • San Mateo, California, United States, 94401
      • Mills-Peninsula Health Services
    • Santa Clarita, California, United States, 91321
      • Care Access Research - Santa Clarita
    • Tarzana, California, United States, 91356
      • Metabolic Institute of America
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
    • Longmont, Colorado, United States, 80501
      • IMMUNOe International Research Centers - Longmont
  • Connecticut
    • Hamden, Connecticut, United States, 06517
      • Chase Medical Research of Greater New Haven
  • Florida
    • Fort Lauderdale, Florida, United States, 33312
      • The Center for Diabetes and Endocrine Care
    • Fort Lauderdale, Florida, United States, 33316
      • M & O Clinical Research
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty Inc.
    • Homestead, Florida, United States, 33032
      • Homestead Associates in Research
    • Miami, Florida, United States, 33186
      • Med Research of Florida
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research - Pasco County
    • Orlando, Florida, United States, 32825
      • Florida Institute for Clinical Research, LLC
    • Ormond Beach, Florida, United States, 32174
      • Ormond Beach Clinical Research
    • Palm Harbor, Florida, United States, 34684
      • Suncoast Clinical Research - Pinellas County
    • Spring Hill, Florida, United States, 34609
      • Meridien Research - Spring Hill
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
    • Columbus, Georgia, United States, 31904
      • IACT Health - Columbus Regional Medical Group Endocrine Consultants - Columbus
    • Newnan, Georgia, United States, 30265
      • IACT Health - Columbus Regional Medical Group Endocrine Consultants
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • 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
      • Kentucky Diabetes Endocrinology Center
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Bay West Endocrinology Associates
    • Camp Springs, Maryland, United States, 20746
      • BTC Network - Capital Diabetes and Endocrine Associates - Camp Springs
    • Rockville, Maryland, United States, 20852
      • Endocrine & Metabolic Consultants
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Quality Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center
  • New Jersey
    • Brick, New Jersey, United States, 08723
      • BTC Network - Garden State Endocrinology - Brick
  • New York
    • Albany, New York, United States, 12206
      • The Endocrine Group, LLP
    • New Hyde Park, New York, United States, 11042
      • North Shore Diabetes and Endocrine Associates
    • Staten Island, New York, United States, 10301
      • University Physicians Group
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Greenville, North Carolina, United States, 27834
      • Physicians East - Greenville
    • Morehead City, North Carolina, United States, 28557
      • Carteret Medical Group - Morehead City
  • Ohio
    • Columbus, Ohio, United States, 43201
      • Endocrinology Research Associates
    • Mentor, Ohio, United States, 44060
      • Your Diabetes Endocrine Nutrition Group, Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Intend Research
    • Stillwater, Oklahoma, United States, 73111
      • Lynn Institute of Stillwater
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Care Access Research - Warwick
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes & Endocrine Consultants
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Medical Specialists
    • Austin, Texas, United States, 78704
      • Austin Regional Clinic
    • Austin, Texas, United States, 78731
      • Texas Diabetes & Endocrinology - Central Austin
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75231
      • Research Institute of Dallas
    • El Paso, Texas, United States, 79935
      • El Paso Medical Research Institute
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • Pflugerville, Texas, United States, 78660
      • Austin Regional Clinic - Kelly Lane
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio
    • Victoria, Texas, United States, 77901
      • Crossroads Clinical Research

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, non-lactating female subjects between the ages of 18 and 75 years, inclusive.
2. Female subjects of child-bearing potential, willing to use contraceptive method(s), agreed by the Investigator, to prevent pregnancy during the study.
3. 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.
4. Ability to understand and fully comply with all study procedures and restrictions.
5. A confirmed diagnosis of T1DM and who have been on an approved basal-bolus insulin regimen for at least 6 months prior to Screening. The type or brand of insulins should not have changed in the 6 months before Screening.
6. Do not expect to change the brand or type of their basal insulin during the study.
7. C-peptide ≤ 1.0 ng/mL
8. HbA1c ≤ 10.0%
9. Body mass index (BMI) ≥ 19 kg/m2 and ≤ 35 kg/m2
10. Adherence to a prudent diet and exercise regimen recommended by the medical provider in accordance with local standard of care or American Diabetes Association recommendations, and willingness to maintain this regimen consistently for the duration of the study.

Exclusion Criteria:

1. Participation in another clinical study within 30 days or 5 half-lives of last dose of experimental medication before Screening, whichever is longer.
2. Previous use of Gan & Lee Insulin Lispro Injection.
3. Use of insulin neutral protamine hagedorn or insulin detemir within 6 months prior to study entry.
4. Current or expected use of an insulin pump or use of continuous glucose measurement to monitor blood glucose during the study.
5. Diabetic ketoacidosis (DKA) within 6 months before Screening.
6. Brittle T1DM within 1 year before Screening, defined as more than 2 hospitalizations related to diabetes mellitus (excluding hospitalizations for diagnostic purposes), and/or severe hypoglycemia for which the subject experiences severe cognitive impairment requiring external assistance for recovery.
7. Renal replacement therapy required or with an estimated (or measured) glomerular filtration rate < 15 mL/min (Modification of Diet in Renal Disease calculation).
8. Any clinically significant cardiovascular (CV) or cerebrovascular event, e.g., myocardial infarction (MI), acute coronary syndrome (ACS), recent revascularization (including coronary artery bypass graft procedures [CABG], percutaneous coronary intervention [PCI]), transient ischemic attack (TIA), or hemorrhagic or ischemic stroke within 3 months before Screening.
9. History of congestive heart failure defined as New York Heart Association (NYHA) Stage III or IV.
10. Inadequately controlled or unstable hypertension as defined by a systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg at Screening and/or Randomization.
11. Inadequately controlled thyroid disease, as reflected by abnormal TSH and free T4 values. (Hypothyroid or hyperthyroid conditions should be resolved or stabilized before Screening according to local standard of care).
12. Any clinically significant (in the opinion of the Investigator) hematology, chemistry, or urinalysis test results at Screening, including any liver function test > 3X of the upper limit of normal (ULN) or bilirubin > 1.5X of the ULN (subjects with elevated bilirubin due to Gilbert syndrome are eligible to participate, if such tests were performed in the past).
13. Autonomic neuropathy resulting in a diagnosis of gastroparesis.
14. Hemoglobin < 12 g/dL for males or < 11 g/dL for females at Screening.
15. Hospitalization within the 14 days before Screening, or planned hospitalization at any time during the study.
16. Newly prescribed or high-dose (60 mg/day prednisone or equivalent) treatment with glucocorticosteroids, immunosuppressants, or cytostatic agents due to disorders of the immunological system, such as rheumatoid arthritis, psoriasis, spondyloarthritis, and asthma, within 60 days before Screening (Medications under following scenario are allowed: chronically administered oral, inhaled, topical, or intra-articular corticosteroids at a stable dosage; stable therapy with disease modifying agents [e.g., methotrexate, sulfasalazine]; disease is inactive [e.g., remission, well controlled stable phase]; and no significant changes in treatment scheme are expected).
17. History of human immunodeficiency virus (HIV) or Hepatitis B or Hepatitis C infections.
18. Any unresolved infection or a history of active infection within 30 days before screening other than mild viral illness (as judged by the Investigator).
19. Current use of other medications for diabetes treatment, such as dipeptidyl peptidase 4 inhibitors (DPP4i), glucagon-like peptide 1 receptor agonists (GLP1-R), or sodium glucose cotransporter 2 inhibitors (SGLT2i) (See Appendix 1 [Section 16.1] for a list of prohibited medications).
20. A history of alcohol use of more than two drinks a day on average for the last year, or a history of alcohol or substance abuse within 2 years before Screening.
21. Previous (within 3 months before Screening) or anticipated treatment with interferons.
22. History of malignancy (except for treated non-melanoma skin cancer and treated cervical adenocarcinoma in situ) within 5 years before Screening
23. Receiving blood transfusion or undergoing plasmapheresis within 6 months before Screening.
24. History of splenectomy.
25. Intolerance or history of hypersensitivity to insulin lispro or any excipient of the study drugs.
26. Any other clinically significant medical or psychiatric condition, or one requiring further evaluation that in the opinion of the Investigator could interfere with conduct of the study or interpretation of the data.

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: Experimental: Gan & Lee Insulin Lispro Injection; Gan & Lee Insulin Lispro Injection for subcutaneous injection, 100 U/mL, in a disposable multidose pen injector with a pre-filled 3-mL type I glass cartridge. Subjects randomized to the Gan & Lee Insulin Lispro Injection group will participate in the study for 26 weeks.	Biological: Gan & Lee Insulin Lispro Injection; Route of administration: subcutaneous injection
Active Comparator: Active Comparator: Humalog; EU-authorized Humalog KwikPen® - insulin lispro injection, solution for subcutaneous injection, 100 U/mL (pre-filled). Subjects randomized to the Humalog group will participate in the study for 26 weeks.	Biological: Humalog; Route of administration: subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment developed AIAs or important increase in AIA titers	The percentage of subjects in each treatment group who develop treatment induced AIAs, defined as newly confirmed positive AIA development or important (at least a 4-fold) increase in titers after baseline and up to visit Week 26.	Week 1 to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with negative AIA at baseline who develop 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.	Week 1 to Week 26
Percentage of subjects with important increase in titers	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.	Week 1 to Week 26
Mean change from baseline in AIA titers	The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26.	Week 1 to Week 26
Percentage of subjects with confirmed positive AIA who develop anti-insulin NAbs	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 NAbs after baseline and up to visit Week 26.	Week 1 to Week 26
Percentage of subjects with positive AIA after baseline	The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.	Week 1 to Week 26
Incidence and severity of all treatment-emergent adverse events	The incidence and severity of all treatment-emergent adverse events and the following subgroups: Adverse events of special interest. Serious adverse events, including fatal events. Adverse events leading to termination of the study treatment and/or early withdrawal from the study. Treatment-related adverse events. IP device-related adverse events. Injection site reactions. The incidence of clinically significant laboratory abnormalities. The incidence of clinically significant abnormalities in physical examination and vital signs.	Week 1 to Week 26
Change from baseline in HbA1c at visit Week 26	Change from baseline in HbA1c at visit Week 26 in each treatment group.	Week 1 to Week 26
Percentage of subjects who achieve an HbA1c of ≤ 7.0% at visit Week 26	The number and percentage of subjects who achieve an HbA1c of ≤ 7.0% at visit Week 26 in each treatment group.	Week 1 to Week 26

Collaborators and Investigators

• Sponsor: Gan and Lee Pharmaceuticals, USA
• Investigators: Study Director: Jia Lu, PhD, Gan & Lee Pharmaceuticals, USA

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Actual): January 27, 2020
• Study Completion (Actual): January 27, 2020

Study Registration Dates

• First Submitted: January 13, 2020
• First Submitted That Met QC Criteria: February 2, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 2, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Diabetes Mellitus; Lispro; Basal; Diabetes Type 1; 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 Lispro
• Other Study ID Numbers: GL-LSPT1-3003

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