Effect of Otelixizumab in New-Onset Type 1 Diabetes Mellitus (NOT1DM)

• Conditions: OT1DM is an autoimmune disease. This means that the immune system, the part of the body which usually helps to fight infections, mistakenly attacks cells that produce insulin in the body. Insulin is necessary for the uptake of sugar from the blood; MedDRA version: 18.0Level: LLTClassification code 10003814Term: Autoimmune disease, not elsewhere classifiedSystem Organ Class: 100000004870; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2013-003296-34-BE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-18
• Last Update Posted: 6 October 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or female aged between 16 and 27 years of age inclusive, at the time of signing the informed consent.
NOTE: Subjects aged 16 to 17 years must be Tanner Stage = 2 (see SPM). All subjects must weigh at least 31 kg.
2. Diagnosis of diabetes mellitus according to ADA and WHO criteria and consistent with Type 1a (autoimmune) DM, with an interval of approximately 28 days (not more than 32 days) between the initial diagnosis and the first dose of study drug).
Written documentation of the diagnosis of DM, including the date of diagnosis, must be obtained from the diagnosing physician.
3. Currently requires insulin treatment for T1DM and has received insulin therapy for at least 7 days prior to screening.
4. Positive for at least one autoantibody associated with T1DM:
antibody to glutamic acid decarboxylase (anti GAD), antibody to protein tyrosine phosphatase-like protein (anti IA 2), antibody to islet-cell antigen (ICA) or ZnT8 Autoantibody.
5. Evidence of residual functioning ß cells as measured by mixed meal stimulated C peptide peak level = 0.2 nmol/L.
6. A female subject is eligible to participate if she has a negative pregnancy test as determined by a urine hCG test at screening or prior to dosing AND
- Agrees to use one of the contraception methods listed in Section 4.3.1. Female subjects must agree to use contraception for 2 weeks prior to dosing and for 60 days after the last dose of study drug.
- OR has only same-sex partners (refrains from heterosexual intercourse), when this is her preferred and usual lifestyle.
7. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 4.3.1. This criterion must be followed from 2 weeks prior to dosing and for 60 days after the last dose of study drug.
8. Willing to follow the procedures outlined in the protocol.
9. AST and ALT < 2xULN; alkaline phosphatase and bilirubin ? 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
10. Subjects eligible for enrolment in the study must meet all of the following criteria:
- QTc <450msec or
- QTc <480msec for patients with bundle branch block
The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB), Fridericia’s formula (QTcF), or another method, machine or manual overread.
- For subject eligibility and withdrawal, QTcF will be used.
- For purposes of data analysis, QTcF will be used as primary.
The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
11. Screening total lymphocyte counts within the normal range in two separate samples taken at least three days apart (eg screening and Day -1).
12. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. In the case of minors (under 18 years) written informed consent must also be obtained from a parent or Legally Acceptable Representative (LAR).
Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. A positive pre-study Hepatitis B surface antigen or core antibody or positive
Hepatitis C antibody result within 3 months of screening.
2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
3. A positive test for HIV 1 and/or 2 antibody.
4. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
5. Exposure to more than four new investigational drugs within 12 months prior to the first dosing day.
6. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or CRO/GSK Medical Monitor, contraindicates their participation.
7. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 3 month period.
8. Lactating females.
9. Subject is mentally or legally incapacitated.
10. History of thrombocytopenia.
11. The subject has received immunization with a vaccine within 4 weeks before the first dose of study drug or requires a vaccine within 30 days after the last dose of study drug
12. The subject has had significant systemic infection during the 6 weeks before the first dose of study drug (e.g., infection requiring hospitalisation, major surgery, or i.v. antibiotics to resolve; other infections, e.g., bronchitis, sinusitis, localised cellulitis, candidiasis, or urinary tract infections, must be assessed on a case-by-case basis by the investigator regarding whether they are serious enough to warrant exclusion).
13. Current or prior malignancy, other than non-melanoma skin cancer.
14. Patient has undergone a splenectomy
15. Radiological evidence of active tuberculosis (TB).
16. Significant and/or active disease in any body system likely to increase the risk to the subject or interfere with the subject’s participation in or completion of the study. Examples of significant diseases include, but are not limited to, coronary artery disease, congestive heart failure, uncontrolled hypertension, renal failure, emphysema, history of bleeding peptic ulcers, history of seizure(s), addiction to illicit drugs, and alcohol abuse.
17. Clinically significant (based on Investigator’s discretion in consultation with the Medical Monitor if second opinion required) abnormal laboratory values during the screening period, other than those due to T1DM. A clinically significant abnormal value will not result in exclusion if, upon retest, the abnormality is resolved or becomes clinically insignificant.
18. Positive EBV capsid Ab IgM in absence of a positive EBV EBNA Ab IgG
19. EBV viral load of> 10,000 copies per 106 peripheral blood mononuclear cells
(PBMCs) as determined by quantitative polymerase chain reaction (qPCR)..
20. IgG negative for EBV.
21. A positive result on a test for syphilis; and if result of the first test is positive, then a confirmatory test using another method will be performed.
22. Have used any atypical antipsychotic drug (e.g., risperidone [Risperdal], quetiapine [Seroquel], or clozapine [Clozaril]) within the 30 days before signing the ICF.
23.

Study & Design

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