GanLee cancelled study -FDA Draft Guidance: "Clinical Immunogenicity Considerations for Biosimilar & Interchangeable Insulin Products" released 11/25/2019

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

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.