Gan & Lee Evaluation of New Biosimilar for Type 1 Lispro

Diabetes Mellitus, Type 1 Clinical Trial

— GENTL 1  

Official title:

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04254380
• Other study ID #: GL-LSPT1-3003
• Status: Withdrawn
• Phase: Phase 3
• Start date: December 4, 2019
• Est. completion date: January 27, 2020

Study information

• Verified date: February 2020
• Source: Gan and Lee Pharmaceuticals, USA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 27, 2020
• Est. primary completion date: January 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Biological:
• Gan & Lee Insulin Lispro Injection
Route of administration: subcutaneous injection
• Humalog
Route of administration: subcutaneous injection

Locations

Country	Name	City	State
Czechia	Diabetologie Ceské Budejovice s.r.o	Ceské Budejovice	Jihocesky KRAJ
Czechia	Diahaza s.r.o.	Holešov
Czechia	StefaMed	Hradec Králové
Czechia	Clintrial	Praha 10
Czechia	Milan Kvapil s.r.o	Praha 11
Germany	Diabeteszentrum DO	Dortmund
Germany	Diabetes Schwerpunktpraxis	Duisburg
Germany	Diabetes-falkensee.de - Zentrum für klinische Studien	Falkensee
Germany	RED-Institut GmbH	Oldenburg
Germany	Diabetologische Praxis	Saarlouis
Hungary	Lausmed Egeszsegugyi es Szolgaltato Kft.	Baja
Hungary	Bajcsy-Zsilinszky Kórház és Rendelointézet	Budapest
Hungary	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet	Budapest
Hungary	Trantor 99 Bt Anyagcsere Centrum	Budapest
Hungary	Debreceni Egyetem Kenézy Gyula Egyetemi Kórház	Debrecen
Hungary	Békés Megyei Központi Kórház Pándy Kálmán Tagkórház	Gyula
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Hungary	Kanizsai Dorottya Kórház	Nagykanizsa
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
Hungary	Medical-Expert Kutatási - Kísérleti és Szolgáltató Kft	Veszprém
Hungary	Zala Megyei Szent Rafael Kórház	Zalaegerszeg
Poland	Centrum Badan Klinicznych PI-House	Gdansk
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Gdanska Poradnia Cukrzycowa	Gdansk
Poland	Centrum Medyczne Pratia Gdynia	Gdynia
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	NZOZ Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne "Diab-Endo-Met"	Kraków
Poland	Pratia MCM Kraków	Kraków
Poland	Bogdan Walko Niepubliczny Zaklad Opieki Zdrowotnej Przychodnia Specjalistyczna MEDICA	Lublin
Poland	CenterMed Lublin Sp. z o.o	Lublin
Poland	KO-MED Centra Kliniczne Lublin - Królewska	Lublin
Poland	Centrum Medyczne Grunwald	Poznan
Poland	Nasz Lekarz Przychodnie Medyczne	Torun
Poland	AMED Centrum Medyczne	Warszawa
Poland	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie	Warszawa
Poland	Centrum Medyczne K2J2	Wolomin
Poland	Centrum Medyczne Oporów	Wroclaw
Poland	Regionalna Poradnia Diabetologiczna	Wroclaw
Spain	Hospital de la Santa Creu i de Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Complejo Hospitalario Universitario de Ferrol	Ferrol
Spain	Complejo Hospitalario Universitario La Coruña (Gerencia de Gestión Integrada de A Coruña)	La Coruña
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Fundació Hospital de l'Esperit Sant	Santa Coloma de Gramenet
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Nuevas Tecnologías en Diabetes y Endocrinología	Sevilla
United States	The Endocrine Group, LLP	Albany	New York
United States	Amarillo Medical Specialists	Amarillo	Texas
United States	Advanced Research Center	Anaheim	California
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	Austin Regional Clinic	Austin	Texas
United States	Texas Diabetes & Endocrinology - Central Austin	Austin	Texas
United States	Bay West Endocrinology Associates	Baltimore	Maryland
United States	BTC Network - Garden State Endocrinology - Brick	Brick	New Jersey
United States	BTC Network - Capital Diabetes and Endocrine Associates - Camp Springs	Camp Springs	Maryland
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	Cedar Crosse Research Center	Chicago	Illinois
United States	Endocrinology Research Associates	Columbus	Ohio
United States	IACT Health - Columbus Regional Medical Group Endocrine Consultants - Columbus	Columbus	Georgia
United States	Midwest CRC	Crystal Lake	Illinois
United States	Research Institute of Dallas	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	El Paso Medical Research Institute	El Paso	Texas
United States	M & O Clinical Research	Fort Lauderdale	Florida
United States	The Center for Diabetes and Endocrine Care	Fort Lauderdale	Florida
United States	Valley Research	Fresno	California
United States	PharmQuest	Greensboro	North Carolina
United States	Physicians East - Greenville	Greenville	North Carolina
United States	Chase Medical Research of Greater New Haven	Hamden	Connecticut
United States	Sweet Hope Research Specialty Inc.	Hialeah	Florida
United States	Homestead Associates in Research	Homestead	Florida
United States	Pioneer Research Solutions	Houston	Texas
United States	Palm Research Center	Las Vegas	Nevada
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	IMMUNOe International Research Centers - Longmont	Longmont	Colorado
United States	Angel City Research, Inc.	Los Angeles	California
United States	Your Diabetes Endocrine Nutrition Group, Inc.	Mentor	Ohio
United States	Med Research of Florida	Miami	Florida
United States	Carteret Medical Group - Morehead City	Morehead City	North Carolina
United States	North Shore Diabetes and Endocrine Associates	New Hyde Park	New York
United States	Suncoast Clinical Research - Pasco County	New Port Richey	Florida
United States	IACT Health - Columbus Regional Medical Group Endocrine Consultants	Newnan	Georgia
United States	Intend Research	Norman	Oklahoma
United States	California Medical Research Association	Northridge	California
United States	Quality Clinical Research	Omaha	Nebraska
United States	Florida Institute for Clinical Research, LLC	Orlando	Florida
United States	Ormond Beach Clinical Research	Ormond Beach	Florida
United States	Suncoast Clinical Research - Pinellas County	Palm Harbor	Florida
United States	Austin Regional Clinic - Kelly Lane	Pflugerville	Texas
United States	Endocrine & Metabolic Consultants	Rockville	Maryland
United States	Endocrine Research Solutions	Roswell	Georgia
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Mills-Peninsula Health Services	San Mateo	California
United States	Care Access Research - Santa Clarita	Santa Clarita	California
United States	Northeast Clinical Research of San Antonio	Schertz	Texas
United States	Meridien Research - Spring Hill	Spring Hill	Florida
United States	University Physicians Group	Staten Island	New York
United States	Lynn Institute of Stillwater	Stillwater	Oklahoma
United States	Metabolic Institute of America	Tarzana	California
United States	Crossroads Clinical Research	Victoria	Texas
United States	Care Access Research - Warwick	Warwick	Rhode Island
United States	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa
United States	Metabolic Research Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gan and Lee Pharmaceuticals, USA

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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