A Phase IIa, open-label, dose-titration, multicenter study to assess the safety and preliminary efficacy of NI-0401 in patients with acute cellular renal allograftt rejectio

Phase 1

• Conditions: Acute cellular renal allograft rejection.

• Registration Number: EUCTR2007-001857-24-PL
• Lead Sponsor: ovImmune S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-09-24
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

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.

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) yes
F.1.3.1 Number of subjects for this age range

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.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To assess changes in renal function overtime, as measured by serum creatinine.<br>To establish NI-0401 pharmacokinetics in patients with BpACR.<br>To assess pharmacodynamics of NI-0401.<br>To quantify the level of recurrent rejections, their severity and response to treatment.<br>To assess the incidence of anti-NI-0401 antibodies.<br>;Primary end point(s): Adverse events (nature, frequency, intensity, causality, seriousness, treatability and outcome).<br>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.<br>;Main Objective: To assess safety and tolerability of NI-0401<br>To determine whether NI-0401 can reverse BpACR