Clinical trial NCT03371108: Gan & Lee Insulin Glargine Target Type (2) Evaluating Research
Official title: 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 2 DIABETES MELLITUS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Diabetes Type 2
Type 2
Basal
Insulin
Glargine
T2DM
Diabetes Mellitus
Lead sponsor: Gan and Lee Pharmaceuticals, USA
Sponsor class: INDUSTRY
First posted: 2017-12-13
Enrollment: 567
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 study eligibility criteria will be centrally randomized 1:1 in an open-label fashion to receive either Gan \& Lee Insulin Glargine Injection or Lantus® for 26 weeks.
Primary purpose: TREATMENT

Brief summary: 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 (AIA) at baseline who develop confirmed positive AIA up to Week 26, the percentage of subjects with at least a 4-fold increase in titers compared to baseline value, mean change from 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 the percentage of subjects in each treatment group with confirmed positive AIA up to visit Week 26

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®


Eligibility criteria: 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 2 diabetes mellitus who meet one of the following:

   1. If insulin-naïve, subjects should have been on at least 2 approved OAMs for at least 12 weeks before screening, and the clinician has decided to add insulin therapy.
   2. If already being treated with a basal and/or bolus insulin, subjects should have been treated with insulin for at least 6 months in addition to at least 1 approved OAM, and must not have changed the type or brand of insulin within 6 months prior to screening.
5. HbA1c values as follows:

   1. If insulin-naïve, HbA1c ≤ 11.0%.
   2. If previously on a basal insulin regimen, HbA1c ≥ 7.0% and ≤ 11.0%.
6. Body mass index (BMI) ≤ 45 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 2 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 \> 45 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 concomitant 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.

Primary outcomes:
measure: Treatment-induced Anti-Insulin Antibody (TI-AIA) is the Primary Endpoint
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: CFB in HbA1c to Week 26
timeFrame: Baseline to Week 26
measure: Immunogenicity - Percentage of Subjects in Each Treatment Group With Negative AIA at Baseline Who Develop Confirmed Positive AIA After Baseline
timeFrame: Baseline to Week 26
measure: Immunogenicity - Percentage of Subjects in Each Treatment Group With Confirmed Positive AIA at Baseline Who Developed at Least a 4-fold Increase in Titers After Baseline
timeFrame: Baseline to Week 26
measure: Immunogenicity - Mean Change From Baseline in Each Treatment Group in AIA Titers After Baseline
timeFrame: Baseline to Week 26
measure: Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline Who Develop Any Anti-insulin Neutralizing Antibodies After Baseline
timeFrame: Baseline to Week 26
measure: Immunogenicity - Percentage of Subjects With Confirmed Positive AIA After Baseline
timeFrame: Baseline to Week 26
measure: Efficacy - Postbaseline FBG Control
timeFrame: Baseline to Week 26
measure: Efficacy - HbA1c Control
timeFrame: At Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Simon Williamson Clinic
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tuscumbia
country: United States
facility: Terence T. Hart, MD
state: Alabama
city: Phoenix
country: United States
facility: Family Practice Specialists
state: Arizona
city: Fresno
country: United States
facility: Valley Research
state: California
city: Newport Coast
country: United States
facility: The Rose Salter Medical Research Foundation
state: California
city: Northridge
country: United States
facility: California Medical Research Association
state: California
city: Sacramento
country: United States
facility: Northern California Research Corp.
state: California
city: Hamden
country: United States
facility: CMR of Greater New Haven, LLC
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Fort Lauderdale
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Homestead
country: United States
facility: Homestead Associates in Research
state: Florida
city: Miami
country: United States
facility: Biotech Pharmaceutical Group, LLC
state: Florida
city: Miami
country: United States
facility: Genoma Research Group
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute, LLC
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Ormond Beach
country: United States
facility: Peninsula Research
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute
state: Florida
city: Blue Ridge
country: United States
facility: River Birch Research Alliance, LLC
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Marietta
country: United States
facility: Sestron Clinical Research
state: Georgia
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger Jr. Hospital of Cook County
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: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Methuen
country: United States
facility: ActivMed Practices and Research - Methuen
state: Massachusetts
city: Las Vegas
country: United States
facility: Palm Research Center, Inc.
state: Nevada
city: Greenville
country: United States
facility: Physicians East, PA
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: Columbus
country: United States
facility: Endocrinology Associates, Inc.
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research
state: Ohio
city: Greer
country: United States
facility: Mountain View Clinical Research
state: South Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Chattanooga
country: United States
facility: ClinSearch - Clinical Research Specialists
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
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: Austin
country: United States
facility: Texas Diabetes & Endocrinology - South Austin
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research
state: Texas
city: Round Rock
country: United States
facility: Texas Diabetes & Endocrinology - Round Rock
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Schertz
country: United States
facility: Northeast Clinical Research of San Antonio
state: Texas
city: Murray
country: United States
facility: Radiant Research
state: Utah
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Burke
country: United States
facility: Burke Internal Medicine & Research
state: Virginia
city: Federal Way
country: United States
facility: Stonesifer Clinical Research
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc.
state: Washington
city: Kenosha
country: United States
facility: Clinical Investigations Specialists-Wisconsin
state: Wisconsin
Study officials:
affiliation: Gan & Lee Pharmaceuticals, USA
name: Jia Lu, PhD
role: STUDY_DIRECTOR
affiliation: Endocrinology Research Associates, Inc.
name: Elena A. Christofides, MD, FACE
role: PRINCIPAL_INVESTIGATOR
References: