Immunogenicity Safety Study of Wockhardt's Recombinant Insulin Analog Glargine in Type 1 Diabetic Patients

Condition(s) targeted: Type I Diabetes

Intervention: Wockhardt's Glargine (Glaritus) (Biological); Sanofi-Aventis' Glargine (Lantus) (Biological)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Wockhardt

Official(s) and/or principal investigator(s):
Rasendrakumar Jha, M.D., Study Director, Affiliation: Wockhardt

Overall contact:
Swati Ranade, Phone: +91 22 26534444, Ext: 6241, Email: sranade@wockhardtin.com

This is an open label, randomized, parallel group comparison of the immunogenicity safety of Wockhardt's recombinant insulin analog Glargine (Glaritus®) and Sanofi-Aventis' recombinant insulin analog Glargine (Lantus®) in Type 1 diabetics.

There are two phases of the study, which are as follows:

1. Phase 1 is a comparative phase in which there will be 2 arms (Lantus® arm and the Glaritus® arm)

2. Phase 2 is a follow up phase only applicable to the Glaritus® Arm.

The study will last for 54 weeks for the patients enrolled in the Glaritus arm and approximately 28 weeks for the patients enrolled in the comparator arm.

Two hundred and forty two patients will be enrolled considering an estimated dropout rate of 15% for a sample size of approximately 105 evaluable patients per arm. The total planned enrollment period for this study is approximately 4 months (120 days).

Official title: An Open Label, Randomized Comparison of the Immunogenicity Safety of Wockhardt's Insulin Analogue Glargine (Glaritus) With Sanofi Aventis' Insulin Analogue Glargine (Lantus) in Type 1 Diabetic Patients

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in HbAlc from baseline to 6 months of treatment between Glaritus and Lantus(as surrogate indicator of change in insulin antibodies titers between the two treatment arms).

Secondary outcome:

Change in HbA1c, anti insulin antibodies (AIA) and insulin neutralizing antibodies (INA).

The percent change at 6 months from the baseline in the level of serum AIA & INA in the Glaritus arm with percent change in the level of serum AIA & INA in the Lantus arm.

The change in the glargine dose between Glaritus arm with Lantus arm after the 3rd and 6th month

The percent change at 12 months from the baseline in the level of serum AIA & INA in the Glaritus arm

Change in HbAlc from baseline to 12 months of treatment in Glaritus arm

In both the groups, the correlation of the immunogenicity with hypoglycemia, local allergic reactions and systemic allergic reactions will be evaluated.

Detailed description: To evaluate and compare the Immunogenicity Safety of Wockhardt's recombinant insulin analogue Glargine (Glaritus®) with Sanofi-Aventis' recombinant insulin analogue Glargine (Lantus®) in the United States on the basis of the effects of the anti insulin antibodies generated following administration of these insulins on their efficacy and safety in Type I Diabetics.

The study is designed with the primary objective of change in HbAlc from baseline to 6 months of treatment between Glaritus and Lantus® USA (as surrogate indicator of change in insulin antibodies titers between the two treatment arms). The secondary objective of the study is to measure the correlation between change in HbA1c from baseline to 6 and 12 months of treatment and change in anti insulin and neutralizing antibodies with insulin dose as covariate. In both the groups, the correlation of the immunogenicity (measured as percentage change in serum AIA & INA) with hypoglycemia, local allergic reactions and systemic allergic reactions will be evaluated. Patient safety will be assessed through the monitoring and reporting of any adverse events including laboratory change(s) that occur during the study.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Patients who have been pre-diagnosed as cases of type-1 diabetes for a period not less than 1 year

2. Patients, who at the time of screening, have fasting C-peptide < 0. 5 nmol/L and have been on an insulin regimen for at least 12 months prior to screening in the trial

3. Patients who have been on a stable basal regimen of recombinant human insulin for at least 3 weeks prior to screening. A stable basal regimen is defined as the dose staying within +/- 15%.

4. Male or Female Patients > 18 and < 45 years of age.

5. Patients with body mass index (BMI) of 18. 0 to 30. 0 kg/m2

6. Patients with glycosylated hemoglobin (HbA1c) levels between 7. 0 and 10%

7. Patients who are cooperative, reliable, and agree to have regular injections of insulin and are willing to comply with protocol procedures.

8. Female patients (non-pregnant and non-lactating with adequate protection from conception). Females of childbearing potential must agree to use an acceptable method of birth control (including barrier-method contraceptives or intrauterine device during the study). Women with history of bilateral tubal ligation, women who have undergone total hysterectomy or women who are two years post-menopausal are also eligible (if within > 18 and < 45 years age limits).

Exclusion Criteria:

1. A Patient who is pregnant (as confirmed by a positive urine pregnancy test) or is currently breast-feeding.

2. A Patient with history of no more than two episode of severe hypoglycemia within the past year

3. A Patient whose requirement for total daily dose of insulin is >1. 4 units/kg.

4. A Patient who has received Wockhardt's Glaritus®, Sanofi- aventis' Lantus® or any other company's insulin glargine for the previous one year

5. A Patient with compromised hepatic or renal function, as shown by, but not limited to, baseline AST or ALT >3 times the upper limit of normal range, serum creatinine >2. 0 mg/dl and/or BUN >30 mg/dl, respectively. Abnormal findings should be discussed with the medical monitor prior to the patient's entry.

6. A Patient who is an employee of the Investigator, or a patient who has a direct involvement with the trial or other trials under the direction of the Investigator.

7. A Patient who has been treated with other investigational agent or devices within the previous 30 days, has planned use of investigational drugs or devices, or has been previously randomized in this trial.

8. A Patient with history or evidence of allergy to insulin preparations.

9. Patient who has received any insulin of animal origin during the last 3 years.

10. A Patients who is currently receiving or has received, within the last year, any immunomodulators medications, including corticosteroids that would possibly modify antibody generation either at the enrollment or during the course of the study. Topical/ ophthalmic/intra-articular/nasal spray corticosteroids will be allowed.

11. Patients who are Hepatitis B or C positive on testing or have positive medical history of HIV at screening.

12. Patients who received an oral hypoglycaemic agent within 4 weeks prior to signing consent form.

13. Has used GLP-1 analog (for example, exenatide) and nasal insulin within 3 months prior to screening

14. Patients who have undergone pancreatectomy or pancreas/islet cell transplant

15. Patient with history or evidence of active severe proliferative retinopathy, nephropathy and/or neuropathy, significant cardiovascular disease (including, but not limited to, myocardial infarction, stroke, peripheral vascular disease, ischemic changes at resting ECG), anemia or hemoglobinopathy, alcohol or drug abuse or any other medical condition that in the opinion of Investigator can interfere with the study.

16. Patients unlikely to comply with the study protocol e. g. unable to return periodically for subsequent visits.

17. Any form of alternative medication including homeopathic, ayurvedic, and herbal are not allowed, 8 weeks prior to the screening and throughout the study duration.

18. A Patient who is diagnosed as hyperthyroid or hypothyroid state at the time of screening will be excluded from the study. However, earlier diagnosed patients (with a history of hyperthyroidism or hypothyroidism) who are well controlled on treatment (Euthyroid) can be considered for enrollment in the study, provided patient is on a stable dose for 1 month prior to screening and is continued on the same dose throughout the study.

19. Patients with a history of unhealed diabetic ulcer

Swati Ranade, Phone: +91 22 26534444, Ext: 6241, Email: sranade@wockhardtin.com

Starting date: July 2011
Last updated: May 10, 2011