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

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00873561
• Other study ID #: NBI 6024-0101
• Status: Completed
• Phase: Phase 1
• First received: March 27, 2009
• Last updated: March 30, 2009
• Start date: December 2001
• Est. completion date: July 2006

Study information

• Verified date: March 2009
• Source: Neurocrine Biosciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCzech Republic: State Institute for Drug ControlFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSouth Africa: Medicines Control CouncilSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: July 2006
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• NBI-6024
0.1, 0.5 or 1 mg NBI-6024 First 3 doses every 2 weeks. Remaining doses given monthly. Total duration of dosing 24 months. Placebo controlled.

Locations

Country	Name	City	State
Canada	Centre de recherche clinique de Laval	Laval
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Center Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Czech Republic	University Hospital and School of Medicine	Olomouc
Czech Republic	Faculty Hospital Motol	Prague
Finland	Helsinki University Hospital	Helsinki
France	Hôpital Debrousse	Lyons
France	Hôpital St Vincent de Paul	Paris
Germany	Diabetes Center for Children and Adolescents	Hannover
Germany	Institut für Diabetesforschung	Munchen
South Africa	New Groote Schuur Hospital	Cape Town
South Africa	Parklands Medical Center	Durban
South Africa	Center for Diabetes and Endocrinology	Johannesburg
South Africa	Donald Gordon Medical Center	Johannesburg
South Africa	Medigate Medical Center	KwaZulu Natal
South Africa	Helderberg Diabetic Clinic and Practice	Somerset West
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de Cruces	Cruces-Baracado
Spain	Hospital Materno-Infantil	Malaga
Spain	University Hospital Virgen del Rocío	Sevilla
United Kingdom	Maternal and Child Health Services 2	Dundee

Sponsors (1)

Lead Sponsor	Collaborator
Neurocrine Biosciences

Countries where clinical trial is conducted

Canada,  Czech Republic,  Finland,  France,  Germany,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		monthly assessments, up to 24 months (end of study)	No
Secondary	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		monthly assessments, up to 24 months (end of study)	Yes