Evaluation of the safety and tolerability of re-dosing with intravenous (IV)otelixizumab in adult subjects with newlydiagnosed type 1 diabetes mellitus.

• Conditions: Autoimmune new onset type 1 diabetes mellitus; MedDRA version: 12.1Level: LLTClassification code 10067584Term: Type 1 diabetes mellitus

• Registration Number: EUCTR2010-019157-17-DE
• Lead Sponsor: GlaxoSmithKline Research and Development LTD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-06-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Male or female, aged 18 to 45 years, inclusive, at the time of anticipated first dose of
study drug.
2. A female subject is eligible to participate if she is of:
a. Non-childbearing potential defined as:
i. pre-menopausal females with a documented tubal ligation or
hysterectomy; or
ii. post-menopausal defined as 12 months of spontaneous
amenorrhoea [in questionable cases a blood sample with
simultaneous follicle stimulating hormone (FSH) > 40 mIU/ml and
estradiol <40pg/ml (<140 pmol/L) is confirmatory].
b. Child-bearing potential and agrees to use one of the contraception methods
listed below:
?? abstinence
?? oral contraceptive, either combined or progestogen alone
?? injectable progestogen
?? implants of levonorgestrel
?? oestrogenic vaginal ring
?? percutaneous contraceptive patches
?? intrauterine device (IUD) or intrauterine system (IUS) that has a
failure rate of <1% per year as stated in the product label
?? male partner sterilisation (vasectomy with documentation of
azoospermia) prior to the female subject’s entry into the study, and this
male is the sole partner for the subject
?? double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository)
Adequate contraception must be used from the beginning of the screening period or
at least 14 days prior to dosing until at least 60 days after the last dose of the second
treatment course of study drug.
Male subjects with partners of childbearing potential must use a barrier method of
contraception from the day of the first dose of study drug until at least 60 days after
the last dose or they must have had a vasectomy. This applies to both dosing
periods.
3. a. Diagnosis of diabetes mellitus according to ADA and WHO criteria (see
Appendix 1), with an interval of = 90 days between the initial diagnosis and the first
dose of study drug. Documentation of the diagnosis of DM, including the date of
diagnosis, must be obtained from the diagnosing physician.
b. History and clinical course consistent with type 1a (autoimmune) DM.

Please refer to the protocol
Are the trial subjects under 18? no
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, breastfeeding, or planning to become pregnant from the beginning of the screening period or at least 14 days prior to initial dosing until at least 60 days after the last dose of the second treatment course of study drug.
2. Current or prior malignancy, other than non-melanoma skin cancer (subject must
have had fewer than 5 occurrences of non-melanoma skin cancer, and the last
occurrence must not be within 3 months of study entry).
3. Clinically significant abnormal laboratory values during the Screening period, other
than those due to T1DM. Permitted ranges for selected laboratory values are shown
in Table 2. A clinically significant abnormal value will not result in exclusion if,
upon re-test, the abnormality is resolved or becomes clinically insignificant.
4. 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.
5. Current or chronic history of liver disease, known hepatic or biliary abnormalities
(with the exception of Gilbert’s syndrome or asymptomatic gallstones), presence of
hepatitis B surface antigen (HBsAg), positive hepatitis C test result within 3 months
of screening
6. Significant systemic infection during the 6 weeks before the first dose of study drug
(e.g., infection requiring hospitalisation, major surgery, or IV 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).
7. History of current or past active tuberculosis infection and or latent tuberculosis
infection (as per Centers for Disease Control [CDC] Guidelines) [Center for Disease
Control and Prevention, 1995]. This eligibility criterion can be met with a negative
purified protein derivative (PPD) test result during Screening or a documented
negative result within 6 months prior to dosing. In specific circumstances (e.g., the
subject has a history of BCG [Bacille Calmette-Guérin] vaccination, a positive
Screening PPD test that is believed to be a false positive result, or the investigator
does not believe it is safe to perform a Screening PPD test), this criterion may be met
by other means following a diagnostic algorithm determined in consultation with the
medical monitor. This diagnostic algorithm will include:
a) A complete clinical evaluation, including, at a minimum, BCG vaccination
history, tuberculosis exposure history, and clinical signs and symptoms suggestive
of tuberculosis infection; and
b) In consultation with the medical monitor, further testing to rule out a false
positive Screening PPD test or to rule out latent tuberculosis in place of a
Screening PPD test may include IFN? testing (e.g., QuantiFERON-TB assay)
and/or chest X-ray.
8. A positive test for human immunodeficiency virus (HIV) antibody or risk factors
which predispose subject to HIV infection.
9. EBV viral load of =10,000 copies per 106 peripheral blood mononuclear cells
(PBMCs) as determined by quantitative polymerase chain reaction (qPCR). If there
is any clinical suspicion that a subj

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 safety, tolerability, and immunogenicity of re-dosing at 6 months<br>with an 8-consecutive day series of otelixizumab intravenous (IV) infusions in<br>adult subjects with newly diagnosed T1DM.;Secondary Objective: To characterise the PK and PD effects following re-dosing.;Primary end point(s): Safety and tolerability:<br>• Adverse Events (AEs).<br>• Change from baseline and number of subjects outside the normal range for<br>blood pressure, respiration rate, heart rate and temperature.<br>• Change from baseline in clinical chemistry and haematology parameters.<br>• Epstein-Barr Virus viral load<br>• Change in total lymphocyte, CD4+ and CD8+ T-cell counts (also a<br>secondary pharmacodynamic endpoint, see below).<br>• Immunogenicity - Serum levels of anti-otelixizumab binding antibodies.<br>Where binding antibodies are detected, proportion which are antiotelixizumab<br>neutralising antibodies.