A Study to Evaluate NBI-6024 in Adult and Adolescent Patients With New Onset of Type 1 Diabetes Mellitus

This was a study designed to evaluate the efficacy of multiple doses of an investigational drug, NBI-6024, in adult (18 to 35 years of age) and adolescent (10 to 17 years of age) patients with new onset type 1 diabetes mellitus, on endogenous insulin production.

A total of 188 patients were enrolled in the study. The study was divided into three periods: screening, treatment (comprising an induction phase and maintenance phase), and follow-up.

NBI-6024 was generally well tolerated and exhibits a benign safety profile, as there were no significant safety issues with NBI-6024 treatment. In summary, NBI-6024 did not demonstrate statistically significant efficacy compared with placebo.

This was a Phase II, multicenter (international), randomized, double-blind, placebo-controlled, parallel, dose-ranging study to evaluate the efficacy of multiple doses of an altered peptide ligand, NBI-6024, in adult (18 to 35 years of age) and adolescent (10 to 17 years of age) patients with new onset type 1 diabetes mellitus.

Study drug was administered subcutaneously a total of 26 times over a 24-month period. The first three doses were administered every 2 weeks (induction phase); all subsequent dosing occurred monthly (maintenance phase). Patients returned to the study center to receive study drug and have efficacy and safety assessments collected. The primary efficacy endpoint was the 2-hour peak C-peptide at Month 24. Other secondary analyses included AUC C-peptide, prescribed insulin usage, AUC blood glucose, HbA1c, hypoglycemic events, and hyperglycemic events.

Eligibility Criteria:
Inclusion Criteria:

* Male or female between the age of 12 and 35 years, inclusive (changed to between the age of 10 and 35 years, inclusive, under Amendment 2)
* If female of childbearing potential, patient must use an acceptable method of birth control prior to and for 30 days post study
* Adult (greater than or equal to 18 years) female patients who were not of childbearing potential must be 2 years postmenopausal, or have had a hysterectomy or tubal ligation
* Were newly diagnosed with type 1 diabetes mellitus
* Presence of one or more of the following:

  * Anti-ICA512 antibodies
  * Anti-GAD antibodies
  * Anti-insulin antibodies, provided that the patient was not on insulin therapy for greater than 1 week
* Body mass index (BMI) \< 28 kg/m2
* Stimulated serum C-peptide peak level between 0.4 pmol/mL and 3.0 pmol/mL, inclusive, at the time of screening
* Laboratory and 12-lead electrocardiogram (ECG) results within normal ranges or, if abnormal, considered by the investigator as non clinically significant for the safety and well being of the patient or for the purposes of the study

Exclusion Criteria:

* Use of an excluded medication/therapy including any of the following:

  * Steroids
  * Oral hypoglycemic agents
  * Chemotherapy and radiation
  * Immunosupressants
  * Nicotinamide \>100 mg per day
  * Any drugs containing sibutramine
* Female patients with a positive pregnancy test or who are lactating
* Adult patients with body weight \<45 kg; adolescent patients with body weight \<30 kg; 10- and 11-year-old patients with body weight \<25 kg
* History of cancer or have existing or actively managed cancer
* History of severe or anaphylactic allergic reactions
* Patients suffering from active skin infections that would prevent subcutaneous injection
* Positive test for HIV antigens, hepatitis B surface antigen, or hepatitis C antibodies
* History of alcohol or substance abuse