A randomized, double-blind, multiple-dose, placebo-controlled, parallel group study to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of ACZ885 in patients with newly diagnosed type-1 diabetes mellitus (T1DM)

• Conditions: Type-1 diabetes mellitus; MedDRA version: 12.1Level: LLTClassification code 10067584Term: Type 1 diabetes mellitus

• Registration Number: EUCTR2010-020166-20-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1.Written informed consent/assent must be obtained before any assessment is performed.
2.Males or females, aged between 6 and 35 years
3.Diagnosis of type 1 diabetes based on American Diabetes Association (ADA) criteria within 3 months of screening and on a stable insulin regimen
4.Presence of at least one diabetes–related autoantibody
5.Peak stimulated C-peptide levels = 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted within one month prior to randomization
6.Willing to forgo vaccinations with ‘live vaccines’ for 18 months (from 3 months prior to first dose until 3 months after the last dose administration). Toxoid-based vaccines such as tetanus, or subunit-based vaccines produced by recombinant technology are allowed
7.Must be willing to comply with intensive diabetes management
8.Must weigh at least 30 kg at study entry
9.Able to communicate well with the investigator, to understand and comply with the requirements of the study.

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.Non-type-1 diabetes (i.e., maturity-onset diabetes of the young (MODY), gestational diabetes, secondary diabetes, idiopathic diabetes, etc.), latent autoimmune diabetes of the adult (LADA).
2.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
3.History of hypersensitivity to the study drug or to drugs of similar chemical classes
4.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are
•women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner
•women whose partners have been sterilized by vasectomy or other means
•using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable)
•Contraception should be maintained throughout the 12 month treatment period and for 3 months after study drug discontinuation.
•Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL; or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six months ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
5.Be currently pregnant or lactating, or anticipate getting pregnant
6.Are immunodeficient or have clinically significant chronic lymphopenia
7.Ongoing Epstein-Barr Virus (EBV) infection
8.An active infection, or febrile illness within 72 hours, or major dental work within 8 days, prior to first dosing
9.A positive test for tuberculosis
10.Immunization with a live vaccine within 3 months of screening
11.Ongoing use of medications known to influence glucose tolerance (eg, systemic steroids)
12.Be currently using non-insulin pharmaceuticals that affect glycemic control
13.Require use of other immunosuppressive agents
14.History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result
15.A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
16.Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct or cause increased risk, eg. pre-existing cardiac disease, neurological, or blood count abnormalities (such as lymphopenia, leukopenia, or thrombocytopenia)
17.Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within 5 years prior to screening.
18.Be currently participating in another type 1 diabetes treatment study
19.History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or baseline

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To assess the effect of ACZ885, in addition to standard of care, on the area under the curve of the stimulated C peptide after a mixed meal tolerance test conducted after 12 months’ treatment.;Secondary Objective: •To assess the effect of ACZ885, in addition to standard of care, on stimulated C-peptide AUC at 4, 7, 10, 18, 24, 30 and 36 months<br>•To assess the effect of ACZ885, in addition to standard of care, on fasting C-peptide at 4, 7, 10, 13, 18, 24, 30 and 36 months<br>•To assess the effect of ACZ885 on the incidence of hypoglycemia<br>•To assess the effect of ACZ885 on the insulin dose<br>•To evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of ACZ885 in subjects with newly-diagnosed type I diabetes mellitus<br>;Primary end point(s): •To assess the effect of ACZ885, in addition to standard of care, on the area under the curve of the stimulated C peptide after a mixed meal tolerance test conducted after 12 months’ treatment.