A multicenter, randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of NI-0401 in patients with newly diagnosed Type 1 Diabetes Mellitus (T1D)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-012988-34-AT
• Date of registration: 19/08/2009
• Prospective Registration: Yes
• Primary sponsor: NovImmune SA
• Public title: A multicenter, randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of NI-0401 in patients with newly diagnosed Type 1 Diabetes Mellitus (T1D)
• Scientific title: A multicenter, randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of NI-0401 in patients with newly diagnosed Type 1 Diabetes Mellitus (T1D)
• Date of first enrolment: 13/10/2009
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012988-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with T1D diagnosed according to the American Diabetes Association 2003 criteria
2. Date of diagnosis within 12 weeks prior to the first dose of study drug
3. Evidence of diabetes associated autoantibodies including at least one of the following: Glutamic acid decarboxylase 65 antibody (GADA); Protein tyrosine phosphatase-like protein IA-2 (IA-2A); Islet cell antibody (ICA)
4. Male or Female patients aged = 12 and = 40 years
5. Fasting C-peptide level ³ 0.25 nmol/l
6. Effective written informed consent
7. EBV-IgG antibody positive
8. Willing to avoid pregnancy during trial participation.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant or lactating women
2. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial or that would prevent patients from providing informed consent.
3. Known or previous diagnosis of malignancies.
4. Current active infections: Any current active infection; Active tuberculosis (TB) within 12 months of study entry or currently undergoingtreatment for TB; Evidence of active or chronic hepatitis including hepatitis B or C; History of or currently active primary or secondary immunodeficiency including known history of HIV infection; Patients with detectable EBV/CMV viral DNA in plasma.
5. Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to baseline.
6. A history of hypersensitivity or allergy to any components of the study regimen.
7. Previous treatment with any cell-depleting therapies, including investigational agents (e.g. alemtuzumab, anti-CD3, anti-CD4, anti-CD5, anti-CD11a, anti-CD19, anti-CD22, anti-BLys/BAFF, or anti-CD20).
8. Treatment with another investigational drug within 3 months or five half-lives of the investigational drug prior to baseline, whichever is longer.
9. Receipt of or need for a live vaccine within 8 weeks prior to and following receipt of study drug treatment.
10. Laboratory tests; WBC count < 2500 x 106/l; CD4 lymphocyte count < 500 x 106/l; ALT > 2 ULN.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Preservation of beta (ß)-islet cell function in patients newly diagnosed with Type 1 Diabetes
MedDRA version: 9.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus

Intervention(s)

Product Code: NI-0401
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: NI-0401
Other descriptive name: Fully human monoclonal antibody directed against the CD3 epsilon chain expressed on all T-cells
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To investigate the effect of NI-0401 on the preservation of ß-islet cell function as demonstrated by the AUC of stimulated C-peptide release.
To investigate the safety of three dose regimens of NI-0401 in patients with newly diagnosed T1D.

Primary end point(s): The mean change from baseline in the AUC of stimulated C-Peptide at Month 6

Secondary Objective: To investigate the effect of therapy with NI-0401 on the metabolic control of T1D demonstrated by regular measurement of: HbA1c over timeo; Insulin requirements over time; Average glucose measurements over time; Episodes of hyper and hypoglycemia.
To assess the pharmacodynamic and immunomodulatory effect of NI-0401 as demonstrated by regular measurement of: extent and duration of CD3-TCR modulation; number of circulating leucocytes and leucocyte subsets; serum pro and anti inflammatory cytokines; mRNA expression in leucocyteso plasma concentration of diabetes associated auto antibodies.
To assess the plasma pharmacokinetics of NI-0401.
To assess the potential for emergent anti-drug antibody and its effect on the efficacy and safety of NI-0401.
To assess the safety and efficacy of a single course vs. two courses of NI-0401 in patients with newly diagnosed T1D.

Secondary ID(s)

NI-0401-04

2009-012988-34-LT