Autoimmune new onset type 1 diabetes mellitus MedDRA version: 12.1 Level: LLT Classification code 10067584 Term: Type 1 diabetes mellitus
Conditions
Interventions
Product Name: GSK2136525
Product Code: GSK2136525
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Otelixizumab
CAS Number: 881191-44-2
Current Sponsor code: GSK2136525
Concentration un
Sponsors
GlaxoSmithKline Research and Development LTD
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, tolerability, and immunogenicity of re-dosing at 6 months with an 8-consecutive day series of otelixizumab intravenous (IV) infusions in 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: • Adverse Events (AEs). • Change from baseline and number of subjects outside the normal range for blood pressure, respiration rate, heart rate and temperature. • Change from baseline in clinical chemistry and haematology parameters. • Epstein-Barr Virus viral load • Change in total lymphocyte, CD4+ and CD8+ T-cell counts (also a secondary pharmacodynamic endpoint, see below). • Immunogenicity - Serum levels of anti-otelixizumab binding antibodies. Where binding antibodies are detected, proportion which are antiotelixizumab neutralising antibodies. | — |
Countries
France, Germany
Outcome results
None listed