Clinical trial NCT04254380: Gan & Lee Evaluation of New Biosimilar for Type 1 Lispro
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes
Diabetes Type 1
Type 1
Basal
Insulin
Lispro
T1DM
Diabetes Mellitus
Insulin Dependent Diabetes
Lead sponsor: Gan and Lee Pharmaceuticals, USA
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment developed AIAs or important increase in AIA titers
timeFrame: Week 1 to Week 26
Secondary outcomes:
measure: Percentage of subjects with negative AIA at baseline who develop positive AIA after baseline
timeFrame: Week 1 to Week 26
measure: Percentage of subjects with important increase in titers
timeFrame: Week 1 to Week 26
measure: Mean change from baseline in AIA titers
timeFrame: Week 1 to Week 26
measure: Percentage of subjects with confirmed positive AIA who develop anti-insulin NAbs
timeFrame: Week 1 to Week 26
measure: Percentage of subjects with positive AIA after baseline
timeFrame: Week 1 to Week 26
measure: Incidence and severity of all treatment-emergent adverse events
timeFrame: Week 1 to Week 26
measure: Change from baseline in HbA1c at visit Week 26
timeFrame: Week 1 to Week 26
measure: Percentage of subjects who achieve an HbA1c of ≤ 7.0% at visit Week 26
timeFrame: Week 1 to Week 26
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Research Center
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Los Angeles
country: United States
facility: Angel City Research, Inc.
state: California
city: Northridge
country: United States
facility: California Medical Research Association
state: California
city: San Mateo
country: United States
facility: Mills-Peninsula Health Services
state: California
city: Santa Clarita
country: United States
facility: Care Access Research - Santa Clarita
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Longmont
country: United States
facility: IMMUNOe International Research Centers - Longmont
state: Colorado
city: Hamden
country: United States
facility: Chase Medical Research of Greater New Haven
state: Connecticut
city: Fort Lauderdale
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Fort Lauderdale
country: United States
facility: M & O Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Sweet Hope Research Specialty Inc.
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research
state: Florida
city: Miami
country: United States
facility: Med Research of Florida
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research - Pasco County
state: Florida
city: Orlando
country: United States
facility: Florida Institute for Clinical Research, LLC
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Beach Clinical Research
state: Florida
city: Palm Harbor
country: United States
facility: Suncoast Clinical Research - Pinellas County
state: Florida
city: Spring Hill
country: United States
facility: Meridien Research - Spring Hill
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Columbus
country: United States
facility: IACT Health - Columbus Regional Medical Group Endocrine Consultants - Columbus
state: Georgia
city: Newnan
country: United States
facility: IACT Health - Columbus Regional Medical Group Endocrine Consultants
state: Georgia
city: Roswell
country: United States
facility: Endocrine Research Solutions
state: Georgia
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Crystal Lake
country: United States
facility: Midwest CRC
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Research Center
state: Iowa
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Baltimore
country: United States
facility: Bay West Endocrinology Associates
state: Maryland
city: Camp Springs
country: United States
facility: BTC Network - Capital Diabetes and Endocrine Associates - Camp Springs
state: Maryland
city: Rockville
country: United States
facility: Endocrine & Metabolic Consultants
state: Maryland
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Brick
country: United States
facility: BTC Network - Garden State Endocrinology - Brick
state: New Jersey
city: Albany
country: United States
facility: The Endocrine Group, LLP
state: New York
city: New Hyde Park
country: United States
facility: North Shore Diabetes and Endocrine Associates
state: New York
city: Staten Island
country: United States
facility: University Physicians Group
state: New York
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Greenville
country: United States
facility: Physicians East - Greenville
state: North Carolina
city: Morehead City
country: United States
facility: Carteret Medical Group - Morehead City
state: North Carolina
city: Columbus
country: United States
facility: Endocrinology Research Associates
state: Ohio
city: Mentor
country: United States
facility: Your Diabetes Endocrine Nutrition Group, Inc.
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Stillwater
country: United States
facility: Lynn Institute of Stillwater
state: Oklahoma
city: Warwick
country: United States
facility: Care Access Research - Warwick
state: Rhode Island
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Medical Specialists
state: Texas
city: Austin
country: United States
facility: Austin Regional Clinic
state: Texas
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology - Central Austin
state: Texas
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: El Paso
country: United States
facility: El Paso Medical Research Institute
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions
state: Texas
city: Pflugerville
country: United States
facility: Austin Regional Clinic - Kelly Lane
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Schertz
country: United States
facility: Northeast Clinical Research of San Antonio
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research
state: Texas
city: České Budějovice
country: Czechia
facility: Diabetologie České Budějovice s.r.o
state: Jihocesky KRAJ
city: Holešov
country: Czechia
facility: Diahaza s.r.o.
city: Hradec Králové
country: Czechia
facility: StefaMed
city: Praha 10
country: Czechia
facility: Clintrial
city: Praha 11
country: Czechia
facility: Milan Kvapil s.r.o
city: Dortmund
country: Germany
facility: Diabeteszentrum DO
city: Duisburg
country: Germany
facility: Diabetes Schwerpunktpraxis
city: Falkensee
country: Germany
facility: Diabetes-falkensee.de - Zentrum für klinische Studien
city: Oldenburg
country: Germany
facility: RED-Institut GmbH
city: Saarlouis
country: Germany
facility: Diabetologische Praxis
city: Baja
country: Hungary
facility: Lausmed Egeszsegugyi es Szolgaltato Kft.
city: Budapest
country: Hungary
facility: Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Kórház és Rendelőintézet
city: Budapest
country: Hungary
facility: Trantor 99 Bt Anyagcsere Centrum
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenézy Gyula Egyetemi Kórház
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház Pándy Kálmán Tagkórház
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Kórház
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatokorhaz
city: Veszprém
country: Hungary
facility: Medical-Expert Kutatási - Kísérleti és Szolgáltató Kft
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház
city: Gdansk
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Gdanska Poradnia Cukrzycowa
city: Gdańsk
country: Poland
facility: Centrum Badań Klinicznych PI-House
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Kraków
country: Poland
facility: Pratia MCM Kraków
city: Kraków
country: Poland
facility: NZOZ Medyczne Centrum Diabetologiczno-Endokrynologiczno-Metaboliczne "Diab-Endo-Met"
city: Lublin
country: Poland
facility: CenterMed Lublin Sp. z o.o
city: Lublin
country: Poland
facility: KO-MED Centra Kliniczne Lublin - Królewska
city: Lublin
country: Poland
facility: Bogdan Walko Niepubliczny Zakład Opieki Zdrowotnej Przychodnia Specjalistyczna MEDICA
city: Poznan
country: Poland
facility: Centrum Medyczne Grunwald
city: Toruń
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne
city: Warszawa
country: Poland
facility: AMED Centrum Medyczne
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnętrznych i Administracji w Warszawie
city: Wołomin
country: Poland
facility: Centrum Medyczne K2J2
city: Wrocław
country: Poland
facility: Regionalna Poradnia Diabetologiczna
city: Wrocław
country: Poland
facility: Centrum Medyczne Oporów
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Ferrol
country: Spain
facility: Complejo Hospitalario Universitario de Ferrol
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario La Coruña (Gerencia de Gestión Integrada de A Coruña)
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramón Y Cajal
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Santa Coloma de Gramenet
country: Spain
facility: Fundació Hospital de l'Esperit Sant
city: Sevilla
country: Spain
facility: Nuevas Tecnologías en Diabetes y Endocrinología
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
Study officials:
affiliation: Gan & Lee Pharmaceuticals, USA
name: Jia Lu, PhD
role: STUDY_DIRECTOR
References: