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

Sponsor

Gan and Lee Pharmaceuticals, USA (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04254380

Collaborator

(none)

Enrollment

107

Locations

Arms

1.8

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Biological: Gan & Lee Insulin Lispro Injection Biological: Humalog	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects who meet the eligibility criteria will be centrally randomized 1:1 in an open-label fashion to receive either Gan & Lee Insulin Lispro Injection or Humalog for 26 weeks. Randomization will be stratified by country.Subjects who meet the eligibility criteria will be centrally randomized 1:1 in an open-label fashion to receive either Gan & Lee Insulin Lispro Injection or Humalog for 26 weeks. Randomization will be stratified by country.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Dec 4, 2019

Actual Primary Completion Date :

Jan 27, 2020

Actual Study Completion Date :

Jan 27, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Treatment developed AIAs or important increase in AIA titers [Week 1 to Week 26]
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.

Secondary Outcome Measures

Percentage of subjects with negative AIA at baseline who develop positive AIA after baseline [Week 1 to Week 26]
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.
Percentage of subjects with important increase in titers [Week 1 to Week 26]
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.
Mean change from baseline in AIA titers [Week 1 to Week 26]
The mean change from baseline in each treatment group in AIA titers after baseline and up to visit Week 26.
Percentage of subjects with confirmed positive AIA who develop anti-insulin NAbs [Week 1 to Week 26]
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.
Percentage of subjects with positive AIA after baseline [Week 1 to Week 26]
The percentage of subjects in each treatment group with confirmed positive AIA after baseline and up to visit Week 26.
Incidence and severity of all treatment-emergent adverse events [Week 1 to Week 26]
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.
Change from baseline in HbA1c at visit Week 26 [Week 1 to Week 26]
Change from baseline in HbA1c at visit Week 26 in each treatment group.
Percentage of subjects who achieve an HbA1c of ≤ 7.0% at visit Week 26 [Week 1 to Week 26]
The number and percentage of subjects who achieve an HbA1c of ≤ 7.0% at visit Week 26 in each treatment group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or nonpregnant, non-lactating female subjects between the ages of 18 and 75 years, inclusive.
Female subjects of child-bearing potential, willing to use contraceptive method(s), agreed by the Investigator, to prevent pregnancy during the study.
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.
Ability to understand and fully comply with all study procedures and restrictions.
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.
Do not expect to change the brand or type of their basal insulin during the study.
C-peptide ≤ 1.0 ng/mL
HbA1c ≤ 10.0%
Body mass index (BMI) ≥ 19 kg/m2 and ≤ 35 kg/m2
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:

Participation in another clinical study within 30 days or 5 half-lives of last dose of experimental medication before Screening, whichever is longer.
Previous use of Gan & Lee Insulin Lispro Injection.
Use of insulin neutral protamine hagedorn or insulin detemir within 6 months prior to study entry.
Current or expected use of an insulin pump or use of continuous glucose measurement to monitor blood glucose during the study.
Diabetic ketoacidosis (DKA) within 6 months before Screening.
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.
Renal replacement therapy required or with an estimated (or measured) glomerular filtration rate < 15 mL/min (Modification of Diet in Renal Disease calculation).
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.
History of congestive heart failure defined as New York Heart Association (NYHA) Stage III or IV.
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.
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).
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).
Autonomic neuropathy resulting in a diagnosis of gastroparesis.
Hemoglobin < 12 g/dL for males or < 11 g/dL for females at Screening.
Hospitalization within the 14 days before Screening, or planned hospitalization at any time during the study.
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).
History of human immunodeficiency virus (HIV) or Hepatitis B or Hepatitis C infections.
Any unresolved infection or a history of active infection within 30 days before screening other than mild viral illness (as judged by the Investigator).
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).
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.
Previous (within 3 months before Screening) or anticipated treatment with interferons.
History of malignancy (except for treated non-melanoma skin cancer and treated cervical adenocarcinoma in situ) within 5 years before Screening
Receiving blood transfusion or undergoing plasmapheresis within 6 months before Screening.
History of splenectomy.
Intolerance or history of hypersensitivity to insulin lispro or any excipient of the study drugs.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Advanced Research Center	Anaheim	California	United States	92805
2	Valley Research	Fresno	California	United States	93720
3	Angel City Research, Inc.	Los Angeles	California	United States	90057
4	California Medical Research Association	Northridge	California	United States	91324
5	Mills-Peninsula Health Services	San Mateo	California	United States	94401
6	Care Access Research - Santa Clarita	Santa Clarita	California	United States	91321
7	Metabolic Institute of America	Tarzana	California	United States	91356
8	University of Colorado School of Medicine	Aurora	Colorado	United States	80045
9	IMMUNOe International Research Centers - Longmont	Longmont	Colorado	United States	80501
10	Chase Medical Research of Greater New Haven	Hamden	Connecticut	United States	06517
11	The Center for Diabetes and Endocrine Care	Fort Lauderdale	Florida	United States	33312
12	M & O Clinical Research	Fort Lauderdale	Florida	United States	33316
13	Sweet Hope Research Specialty Inc.	Hialeah	Florida	United States	33016
14	Homestead Associates in Research	Homestead	Florida	United States	33032
15	Med Research of Florida	Miami	Florida	United States	33186
16	Suncoast Clinical Research - Pasco County	New Port Richey	Florida	United States	34652
17	Florida Institute for Clinical Research, LLC	Orlando	Florida	United States	32825
18	Ormond Beach Clinical Research	Ormond Beach	Florida	United States	32174
19	Suncoast Clinical Research - Pinellas County	Palm Harbor	Florida	United States	34684
20	Meridien Research - Spring Hill	Spring Hill	Florida	United States	34609
21	Metabolic Research Institute	West Palm Beach	Florida	United States	33401
22	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30318
23	IACT Health - Columbus Regional Medical Group Endocrine Consultants - Columbus	Columbus	Georgia	United States	31904
24	IACT Health - Columbus Regional Medical Group Endocrine Consultants	Newnan	Georgia	United States	30265
25	Endocrine Research Solutions	Roswell	Georgia	United States	30076
26	Cedar Crosse Research Center	Chicago	Illinois	United States	60607
27	Midwest CRC	Crystal Lake	Illinois	United States	60012
28	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa	United States	50265
29	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky	United States	40503
30	Bay West Endocrinology Associates	Baltimore	Maryland	United States	21204
31	BTC Network - Capital Diabetes and Endocrine Associates - Camp Springs	Camp Springs	Maryland	United States	20746
32	Endocrine & Metabolic Consultants	Rockville	Maryland	United States	20852
33	Quality Clinical Research	Omaha	Nebraska	United States	68134
34	Palm Research Center	Las Vegas	Nevada	United States	89148
35	BTC Network - Garden State Endocrinology - Brick	Brick	New Jersey	United States	08723
36	The Endocrine Group, LLP	Albany	New York	United States	12206
37	North Shore Diabetes and Endocrine Associates	New Hyde Park	New York	United States	11042
38	University Physicians Group	Staten Island	New York	United States	10301
39	PharmQuest	Greensboro	North Carolina	United States	27408
40	Physicians East - Greenville	Greenville	North Carolina	United States	27834
41	Carteret Medical Group - Morehead City	Morehead City	North Carolina	United States	28557
42	Endocrinology Research Associates	Columbus	Ohio	United States	43201
43	Your Diabetes Endocrine Nutrition Group, Inc.	Mentor	Ohio	United States	44060
44	Intend Research	Norman	Oklahoma	United States	73069
45	Lynn Institute of Stillwater	Stillwater	Oklahoma	United States	73111
46	Care Access Research - Warwick	Warwick	Rhode Island	United States	02886
47	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee	United States	37411
48	Amarillo Medical Specialists	Amarillo	Texas	United States	79106
49	Austin Regional Clinic	Austin	Texas	United States	78704
50	Texas Diabetes & Endocrinology - Central Austin	Austin	Texas	United States	78731
51	Research Institute of Dallas	Dallas	Texas	United States	75231
52	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
53	El Paso Medical Research Institute	El Paso	Texas	United States	79935
54	Pioneer Research Solutions	Houston	Texas	United States	77099
55	Austin Regional Clinic - Kelly Lane	Pflugerville	Texas	United States	78660
56	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
57	Northeast Clinical Research of San Antonio	Schertz	Texas	United States	78154
58	Crossroads Clinical Research	Victoria	Texas	United States	77901
59	Diabetologie České Budějovice s.r.o	České Budějovice	Jihocesky KRAJ	Czechia	370 01
60	Diahaza s.r.o.	Holešov		Czechia	769 01
61	StefaMed	Hradec Králové		Czechia	503 41
62	Clintrial	Praha 10		Czechia	100 00
63	Milan Kvapil s.r.o	Praha 11		Czechia	149 00
64	Diabeteszentrum DO	Dortmund		Germany	44137
65	Diabetes Schwerpunktpraxis	Duisburg		Germany	47051
66	Diabetes-falkensee.de - Zentrum für klinische Studien	Falkensee		Germany	14612
67	RED-Institut GmbH	Oldenburg		Germany	23758
68	Diabetologische Praxis	Saarlouis		Germany	66740
69	Lausmed Egeszsegugyi es Szolgaltato Kft.	Baja		Hungary	6500
70	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet	Budapest		Hungary	1097
71	Bajcsy-Zsilinszky Kórház és Rendelőintézet	Budapest		Hungary	1106
72	Trantor 99 Bt Anyagcsere Centrum	Budapest		Hungary	1213
73	Debreceni Egyetem Kenézy Gyula Egyetemi Kórház	Debrecen		Hungary	4031
74	Békés Megyei Központi Kórház Pándy Kálmán Tagkórház	Gyula		Hungary	5700
75	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár		Hungary	7400
76	Kanizsai Dorottya Kórház	Nagykanizsa		Hungary	8801
77	Markusovszky Egyetemi Oktatokorhaz	Szombathely		Hungary	9700
78	Medical-Expert Kutatási - Kísérleti és Szolgáltató Kft	Veszprém		Hungary	8200
79	Zala Megyei Szent Rafael Kórház	Zalaegerszeg		Hungary	8900
80	Niepubliczny Zaklad Opieki Zdrowotnej Gdanska Poradnia Cukrzycowa	Gdansk		Poland	80-858
81	Centrum Badań Klinicznych PI-House	Gdańsk		Poland	80-546
82	Centrum Medyczne Pratia Gdynia	Gdynia		Poland	81-338
83	Centrum Medyczne Pratia Katowice	Katowice		Poland	40-081
84	Pratia MCM Kraków	Kraków		Poland	30-510
85	NZOZ Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne "Diab-Endo-Met"	Kraków		Poland	31-261
86	CenterMed Lublin Sp. z o.o	Lublin		Poland	20 044
87	KO-MED Centra Kliniczne Lublin - Królewska	Lublin		Poland	20-109
88	Bogdan Walko Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Specjalistyczna MEDICA	Lublin		Poland	20-538
89	Centrum Medyczne Grunwald	Poznan		Poland	60-369
90	Nasz Lekarz Przychodnie Medyczne	Toruń		Poland	87-100
91	AMED Centrum Medyczne	Warszawa		Poland	01-518
92	Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie	Warszawa		Poland	02-507
93	Centrum Medyczne K2J2	Wołomin		Poland	05-230
94	Regionalna Poradnia Diabetologiczna	Wrocław		Poland	50-127
95	Centrum Medyczne Oporów	Wrocław		Poland	52-416
96	Hospital de la Santa Creu i de Sant Pau	Barcelona		Spain	8025
97	Hospital Universitari Vall d'Hebrón	Barcelona		Spain	8035
98	Complejo Hospitalario Universitario de Ferrol	Ferrol		Spain	15405
99	Complejo Hospitalario Universitario La Coruña (Gerencia de Gestión Integrada de A Coruña)	La Coruña		Spain	15006
100	Hospital Universitari Arnau de Vilanova	Lleida		Spain	25198
101	Hospital Universitario de La Princesa	Madrid		Spain	28006
102	Hospital Universitario Ramón Y Cajal	Madrid		Spain	28034
103	Hospital Universitario Virgen de la Victoria	Málaga		Spain	29006
104	Fundació Hospital de l'Esperit Sant	Santa Coloma de Gramenet		Spain	8923
105	Nuevas Tecnologías en Diabetes y Endocrinología	Sevilla		Spain	41003
106	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
107	Hospital Universitario Virgen de Valme	Sevilla		Spain	41014