Clinical trial NCT01308437: Immunosafety Study of Recombinant Human Insulins in Type 1 Diabetics
Official title: An Open Label,Randomized,Comparison of the Immunogenicity and Safety of Wockhardt's Human Insulin Basal Bolus Regimen With the Novo Nordisk's Yeast Based Human Insulin Basal Bolus Regimens, Marketed in United States, in Type 1 Diabetics.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type I Diabetes
Lead sponsor: Wockhardt
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, randomized, parallel group comparison of the immunogenicity safety of Wockhardt's human insulin and isophane insulin compared with the Novo Nordisk's yeast based human insulin products (marketed in USA) 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 (which are described in the section below).
2. Phase 2 is a follow up phase only applicable to Wosulin Arm.

The study will last for 54 weeks for the patients enrolled in Wosulin 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 3 months (90 days).


Eligibility criteria: Inclusion Criteria:

1. Subjects who understand the nature of the study and are willing to provide written informed consent.
2. Subjects who have been pre-diagnosed as cases of type-1 diabetes (fasting C-peptide \< 0.5 nmol/L) and have been on an insulin regimen for at least 12 months prior to inclusion in the trial.
3. Subjects who have been on a stable regimen of recombinant human insulin or analogs for at least 3 months prior to randomization. (A stable regimen is defined as the dose within +/- 10%).
4. Male or female subjects ≥ 18 and \< 55 years of age.
5. Subjects with body mass index (BMI) of ≥18.0 to \< 35.0 kg/m2
6. Subjects with glycosylated hemoglobin (HbA1c) levels between ≥6.5 and \< 9.5%
7. Subjects who are cooperative, reliable, and agree to have regular injections of insulin and are willing to comply with protocol procedures.
8. Female subjects who are not pregnant and non-lactating with adequate protection from conception and fulfilling one of the following criteria are also eligible if within ≥ 18 and \< 55 years age limits:

   1. Women of childbearing potential on an acceptable method of birth control (including but not limited to barrier-method, contraceptives, or intrauterine device)
   2. Women with history of bilateral tubal ligation,
   3. Women who have undergone total hysterectomy
   4. Women who are two years post-menopausal
9. Subjects who are able to use the self glucose-monitoring device and to self inject insulin.

Exclusion Criteria:

1. Female subjects who are pregnant (as confirmed by a positive urine and serum β-HCG) or are currently breast-feeding.
2. Compromised hepatic or renal function, as shown by but not limited to:

   i.Baseline AST or ALT \>3 times the upper limit of normal range, and/or ii.Serum Creatinine \>2.0 mg/dl and/or iii.BUN \>30 mg/dl Abnormal laboratory findings will be discussed with the medical monitor prior to the subject's entry.
3. Employee of Investigator or have direct involvement with trial or other trials under the direction of Investigator.
4. Those treated with other investigational agents or devices within previous 30 days, from screening, have planned use of an investigational drug or device, or have been previously randomized in this trial.
5. History or evidence of allergy to insulin preparations.
6. History or evidence of severe hypoglycemia (severe hypoglycemic episode defined as the subject required glucose, glucagon, orange juice etc administered by a second person)
7. Requirement for total daily dose of insulin is \>1.4 units/kg
8. Who have received Wockhardt's (Wosulin) or Novo Nordisk's Insulin (Novolin® R, Novolin® N, Novolin® 70/30, in US and Actrapid® Insulatard®, and Mixtard® in India) during the previous one year.
9. Serum AIA level \> 20 microU/ml.
10. Receipt of any insulin of an animal origin during the last 3 years.
11. Currently receiving or have 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).
12. Hepatitis B or Hepatitis C or HIV positive.
13. Oral hypoglycaemic agent within 4 weeks prior to signing the consent form.
14. Who have undergone pancreatectomy or pancreas/islet cell transplant.
15. Unlikely to comply with the study protocol e.g. unable to return periodically for subsequent visits.
16. History or evidence of active severe proliferative retinopathy, nephropathy and/or neuropathy significant cardiovascular disease, anemia or hemoglobinopathy, uncontrolled hypothyroidism or uncontrolled hyperthyroidism, alcohol or drug abuse or any other medical condition that in the opinion of Investigator can interfere with the study.
17. Judged by the investigator as inappropriate to participate in the study for any reason other than those mentioned above.

Primary outcomes:
measure: Change in HbAlc from baseline to 6 months of treatment between Wosulin arm and Novolin arm(as surrogate indicator of change in insulin antibodies titers between the two treatment arms).
timeFrame: 6 months
Secondary outcomes:
measure: Correlation between change in HbA1c and change in anti insulin and insulin neutralizing antibodies.
timeFrame: 6 months and 12 months
measure: To compare the change from baseline in the level of serum anti insulin antibodies and insulin neutralizing antibodies between the two arms
timeFrame: 6 months
measure: Compare the change in Insulin dose between the two arms
timeFrame: 3 and 6 months
measure: Correlation of the immunogenicity with hypoglycemia, local allergic reactions and systemic allergic reactions will be evaluated.
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Tustin
country: United States
facility: University Clinical Investigators, Inc. dba Diabetes Research Center
state: California
city: Hialeah
country: United States
facility: International Research Associates
state: Florida
city: Hollywood
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, PA
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Medical Arts Pharmaceutical Research Center
state: Florida
city: Palm Harbor
country: United States
facility: Suncoast Clinical Research
state: Florida
city: Sanford
country: United States
facility: International Clinical Research - US, LLC
state: Florida
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Diabetes & Endocrinology
state: Kansas
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Rockville
country: United States
facility: Endocrine & Metabolic Consultants
state: Maryland
city: Haverhill
country: United States
facility: ActivMed Practices and Research
state: Massachusetts
city: Dearborn
country: United States
facility: Alzohaili Medical Consultants
state: Michigan
city: Rochester
country: United States
facility: ActivMed Practices and Research
state: New Hampshire
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Association
state: Tennessee
city: El Paso
country: United States
facility: Sergio Rovner, MD
state: Texas
city: Salt Lake City
country: United States
facility: Optimum Clinical Research, Inc.
state: Utah
city: Hyderabad
country: India
facility: Dr Rakesh Sahay
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Dia Care - A Complete Diabetes Care Centre
state: Gujrat
city: Karnal
country: India
facility: Dr Sanjay Kalra
state: Haryana
city: Bangalore
country: India
facility: Dr Mala Dharmalingam
state: Karnataka
city: Bangalore
country: India
facility: Bangalore Diabetes Hospital
state: Karnataka
city: Nagpur
country: India
facility: Dr Sharad Pendsey
state: Maharashtra
city: Jaipur
country: India
facility: Diabetes Thyroid &Endocrine Centre
state: Rajasthan
city: Jaipur
country: India
facility: Bhandari's Clinic
state: Rajasthan
Study officials:
affiliation: Wockhardt
name: Ashima Bhatia, M.D.
role: STUDY_DIRECTOR
References: