E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autoimmune new onset type 1 diabetes mellitus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To characterise the PK and PD effects following re-dosing. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 IFNγ 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 subject who is EBV seronegative and with EBV PCR <10,000 copies per 106 PBMCs has symptoms consistent with infectious mononucleosis prior to administration of study drug, then a monospot test result must be negative before the subject can be dosed.
Please refer to the protocol |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |