Clinical trial NCT00873561: A Study to Evaluate NBI-6024 in Adult and Adolescent Patients With New Onset of Type 1 Diabetes Mellitus
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel, Dose-Ranging Study to Evaluate The Efficacy, Safety, Tolerability, and Pharmacodynamics of NBI-6024 In Adult and Adolescent Patients With New Onset Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Keywords: diabetes
type 1
adult
adolescent
new onset
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2009-04-01
Enrollment: 188
Sex: ALL
Minimum age (years): 10
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: To assess the effect of repeated administrations of NBI-6024 on endogenous insulin production as measured by C-peptide levels in adult and adolescent patients with new onset type 1 diabetes mellitus
timeFrame: monthly assessments, up to 24 months (end of study)
Secondary outcomes:
measure: To examine the effects of repeated administrations of NBI-6024 on insulin usage, glycemic control, and immune function (immunodynamics and pharmacodynamics) To examine the safety and tolerability of repeated administrations of NBI-6024
timeFrame: monthly assessments, up to 24 months (end of study)
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Sherbrooke
country: Canada
facility: Center Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Laval
country: Canada
facility: Centre de recherche clinique de Laval
city: Olomouc
country: Czech Republic
facility: University Hospital and School of Medicine
city: Prague
country: Czech Republic
facility: Faculty Hospital Motol
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Lyons
country: France
facility: Hôpital Debrousse
city: Paris
country: France
facility: Hôpital St Vincent de Paul
city: Hannover
country: Germany
facility: Diabetes Center for Children and Adolescents
city: Munchen
country: Germany
facility: Institut für Diabetesforschung
city: Cape Town
country: South Africa
facility: New Groote Schuur Hospital
city: Durban
country: South Africa
facility: Parklands Medical Center
city: Johannesburg
country: South Africa
facility: Center for Diabetes and Endocrinology
city: Johannesburg
country: South Africa
facility: Donald Gordon Medical Center
city: KwaZulu Natal
country: South Africa
facility: Medigate Medical Center
city: Somerset West
country: South Africa
facility: Helderberg Diabetic Clinic and Practice
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cruces-Baracado
country: Spain
facility: Hospital de Cruces
city: Malaga
country: Spain
facility: Hospital Materno-Infantil
city: Sevilla
country: Spain
facility: University Hospital Virgen del Rocío
city: Dundee
country: United Kingdom
facility: Maternal and Child Health Services 2
Study officials:
affiliation: New Groote Schuur Hospital, Capetown, South Africa
name: Areti Philotheou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Walter M, Philotheou A, Bonnici F, Ziegler AG, Jimenez R; NBI-6024 Study Group. No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes. Diabetes Care. 2009 Nov;32(11):2036-40. doi: 10.2337/dc09-0449. Epub 2009 Aug 18.