E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute cellular renal allograft rejection. |
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MedDRA Classification |
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 safety and tolerability of NI-0401 To determine whether NI-0401 can reverse BpACR |
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E.2.2 | Secondary objectives of the trial |
To assess changes in renal function overtime, as measured by serum creatinine. To establish NI-0401 pharmacokinetics in patients with BpACR. To assess pharmacodynamics of NI-0401. To quantify the level of recurrent rejections, their severity and response to treatment. To assess the incidence of anti-NI-0401 antibodies.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women ≥ 18 and ≤ 70 years of age. 2. Recipient of a kidney graft (first or second) from a deceased or living donor (non-HLA-identical). 3. Rise in SCr concentration by > 20% compared to baseline, defined as the most recent creatinine level measured prior to rejection but after transplantation. 4. Allograft biopsy showing evidence of acute cellular rejection, according to Banff 97 criteria. 5. Men and women of childbearing potential must use adequate birth control measures until 6 months after receiving study drug. Therefore, women of childbearing potential and their partners are required to use two forms of contraception. Men with partners of childbearing potential are required to use barrier contraception, in addition to their partners using another method. Acceptable forms of contraception are as follows: - Barrier methods: condoms, diaphragms, cervical caps; - Hormonal contraceptives: combination or progesterone only; Includes depot contraceptives; - Intrauterine methods: intrauterine devices or systems. 6. The screening laboratory tests must meet the following criteria: a. Hb ³ 8.5 g/dL (4.5 mmol/L) b. WBC ³ 2.5 x 109/L c. Neutrophils ³ 1.5 x 109/L d. Platelets ³ 100 x 109/L e. SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper limit of normal range. 7. Patients must be able to adhere to the study visits and protocol requirements. 8. Patients must be able to give written informed consent.
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E.4 | Principal exclusion criteria |
1. Patients who have received therapy with anti-CD3 mAb (OKT3) or anti-lymphocytes polyclonal antibodies (ATG, Atgam) in the past. 2. Patients with cardiac insufficiency or fluid overload (to be excluded by a chest X ray). 3. Severe HLA sensitization (>50% panel reactive antibodies prior to transplantation). 4. Evidence of delayed renal graft function. 5. Have received or are planned to receive immunization with a live vaccine within 6 weeks prior to receiving study drug and 12 weeks after treatment cessation. 6. Concomitant disease: a. Current signs or symptoms of severe, progressive or uncontrolled disease. Patients with cardiac (e.g. recent myocardial infarction or symptomatic ischemic heart disease); pulmonary (e.g. chronic obstructive pulmonary disease); or neurologic disease (e.g. seizure disorder or head trauma). b. Previous diagnosis of, or known, malignancies, except for completely excised basal cell carcinoma. c. Ongoing severe infections, such as hepatitis or pneumonia, or any active infection (requiring therapy). d. History of opportunistic infections such as herpes zoster within 2 months prior to screening. History of active tuberculosis (TB) or currently undergoing treatment for TB. e. Evidence of acute CMV (or D+/R-) or EBV infection. f. Serum anti HCV positive, serum HBsAg positive, serum anti-HIV positive. g. Patients with BK Virus nephropathy. 7. Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation after transplantation (low-dose of aspirin treatment is allowed). 8. Female patients who are pregnant or breast feeding. 9. A psychiatric, addictive, or any other disorder that compromises the ability to give truly informed written consent for participation in this study. 10. Suspected hypersensitivity to any component of the drug product. 11. Has undergone or is undergoing treatment with another investigational drug or approved therapy for investigational use within 3 months prior to entry in this study. Has previously participated in this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events (nature, frequency, intensity, causality, seriousness, treatability and outcome). The percentage of patients demonstrating a complete normalization of SCr at study day 14. Complete normalization is defined as a return of the SCr concentration to < 120% of baseline value.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | Yes |
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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All patients will be followed-up for a minimum of 6 weeks. Patients with SAEs and/or low peripheral T-cells count (≤ 200cells/ μL) will be followed-up till resolution. |
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |