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

Phase 1
Completed
Conditions
Type 1 Diabetes Mellitus
Interventions
Registration Number
NCT00873561
Lead Sponsor
Neurocrine Biosciences
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
188
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1 ExperimentalNBI-6024NBI-6024 0.1 mg
3 ExperimentalNBI-6024NBI-6024 1 mg
2 ExperimentalNBI-6024NBI-6024 0.5 mg
Primary Outcome Measures
NameTimeMethod
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 mellitusmonthly assessments, up to 24 months (end of study)
Secondary Outcome Measures
NameTimeMethod
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-6024monthly assessments, up to 24 months (end of study)

Trial Locations

Locations (21)

University Hospital and School of Medicine

🇨🇿

Olomouc, Czech Republic

Faculty Hospital Motol

🇨🇿

Prague, Czech Republic

Helsinki University Hospital

🇫🇮

Helsinki, Finland

Hôpital Debrousse

🇫🇷

Lyons, France

Donald Gordon Medical Center

🇿🇦

Johannesburg, South Africa

Hôpital St Vincent de Paul

🇫🇷

Paris, France

Center Hospitalier Universitaire de Sherbrooke

🇨🇦

Sherbrooke, Quebec, Canada

Institut für Diabetesforschung

🇩🇪

Munchen, Germany

New Groote Schuur Hospital

🇿🇦

Cape Town, South Africa

Center for Diabetes and Endocrinology

🇿🇦

Johannesburg, South Africa

Hospital de Cruces

🇪🇸

Cruces-Baracado, Spain

Centre de recherche clinique de Laval

🇨🇦

Laval, Canada

Parklands Medical Center

🇿🇦

Durban, South Africa

Diabetes Center for Children and Adolescents

🇩🇪

Hannover, Germany

Medigate Medical Center

🇿🇦

KwaZulu Natal, South Africa

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

Hospital Materno-Infantil

🇪🇸

Malaga, Spain

University Hospital Virgen del Rocío

🇪🇸

Sevilla, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Helderberg Diabetic Clinic and Practice

🇿🇦

Somerset West, South Africa

Maternal and Child Health Services 2

🇬🇧

Dundee, United Kingdom

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