Improving Transplant Opportunities for Patients who are Sensitised (ITOPS)

Phase 1

• Conditions: Highly Sensitised Patients(patients with high levels of human leucocyte antigen specific antibodies) awaiting renal transplantation.These patients are difficult to match to a compatible donor and thus rates of transplantation are low.; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2017-002602-12-GB
• Lead Sponsor: Cardiff and Vale University Health Board

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-12-18
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1.Male or female, aged 18 years and older.
2.Able to give informed consent and willing to fulfil trial requirements.
3.Have completed the necessary assessments to receive a renal transplant.
4.In stable health as determined by the Investigator based on medical history and laboratory tests during the screening period. See Exclusion Criteria for specific exclusions.
5.Negative serological test for hepatitis B (surface antigen and core antibody) and hepatitis C within the last 6 months, and HIV within the last 12 months.
6.Documented immune status to varicella zoster virus (VZV) (at any time).
7.Female participant of childbearing potential must be willing to use a highly effective method of contraception for one year following rituximab (this period will also include the recommended three-month period for avoidance of pregnancy following bortezomib). Male participants must be willing to use a highly effective form of contraception for 3 months post last dose of bortezomib (effective forms of contraception are listed in section 8.10)
8.Persistent (for at least one year) and stable (tested on at least three occasions over the preceding 18 months) circulating HLA antibodies defined by Luminex Single Antigen Bead analysis at the time of recruitment.
9.Recipients awaiting deceased donor transplantation:
ocRF >85% and at least 3 years on the transplant waiting list as determined by the UK deceased donor organ allocation policy for kidney transplantation.
10.Recipients with an HLA incompatible living donor who have been considered for enrolment in the UK Living Kidney Sharing Scheme:
ocRF is >95% or,
ocRF is =85% and they have received no offers after three runs in the UKLKSS.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1.Pregnancy, planned pregnancy during the trial period, or current breast feeding.
2.Active viral, bacterial or fungal infection precluding immunosuppression.
3.Active malignant disease.
4.Patients listed for transplantation of any organ other than kidney alone.
5.History of or active, clinically significant, respiratory, gastrointestinal (including pancreatitis), hepatic, cardiac, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator’s opinion, could affect the conduct of the trial.
6.Have a history of non-adherence, alcohol or substance abuse that, in the judgment of the Investigator, may impair or risk the subject’s full participation in the trial.
7.Positive serological test for hepatitis B, C or HIV.
8.Negative serological test for VZV.
9.Previous graft loss to recurrent primary disease within 2 years of transplantation.
10.Documented intolerance of bortezomib, rituximab or their exipients, or dexamethasone.
11.Persistent thrombocytopaenia, platelet count <100 X 109/L for the past three consecutive months.
12.Persistent neutropaenia, absolute neutrophil count < 2 X 109/L for the past three consecutive months.
13.Hypogammaglobulinaemia, serum IgG less than local laboratory lower limit of normal at screening.
14.Peripheral neuropathy of any grade (reported by symptoms or on clinical examination).
15.Currently involved in any other clinical trial of an investigational medicinal product (IMP) or have taken an IMP within 30 days prior to trial entry except the SIMPLIFIED trial.

Study & Design

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