Clinical trial NCT02475551: Study to Evaluate the Safety, Tolerability, Efficacy and PK of IdeS in Kidney Transplantation
Official title: A Phase II Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Intravenous Ascending Doses of IdeS in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End Stage Kidney Disease
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
Collaborators: name: Uppsala University Hospital
name: Karolinska Institutet
First posted: 2015-06-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will assess the safety and efficacy of IdeS in the transplantation setting. Each patient will receive one dose of IdeS. If the crossmatch test is negative at the time of transplantation, the patient will be transplanted with a kidney from a deceased or living donor. The starting dose will be 0.25 mg/kg BW, given as a single intravenous infusion prior to surgery.

Detailed description: This study will assess the safety and efficacy of the IgG degrading cysteine protease IdeS in the transplantation setting. Patients with DSAs will be treated with IdeS prior to transplantation. Each patient will receive one dose of IdeS. If the crossmatch test is negative after IdeS treatment, the patient will be transplanted with a kidney from a deceased or living donor. Two to four dose groups are planned. Each group will contain 2 patients with the possibility to extend the group to up to 4 patients per group if required for safety and/or efficacy evaluation. The starting dose will be 0.25 mg/kg BW, given as a single intravenous infusion prior to surgery with the possibility to increase the dose in higher dose groups.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with CKD and in dialysis with preformed anti-HLA antibodies (non-DSA, DSA or both), negative T-CDC CXM and at least one antibody MFI \> 3000

Exclusion Criteria:

* Prior malignancy within 2 years excluding adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ and prostate cancer Gleason \<6 and prostate-specific antigen (PSA) \<10 ng/mL.
* Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV
* Clinical signs of ongoing infectious disease.
* Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure \> New York Heart Association (NYHA) grade 3, unstable coronary disease or oxygen dependent chronic obstructive pulmonary disease (COPD)
* History of any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at increased risk because of participation in the study, or influence the results or the patient's ability to participate in the study
* Hypogammaglobulinemia defined as any values of P-total IgG less than 3 g/L
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to IdeS (e. g streptokinase and/or staphylokinase)
* Has received another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical study that included drug treatment within 4 months of the first administration of investigational product in this study.
* Patients consented and screened but not dosed in previous studies are not excluded

Primary outcomes:
measure: safety
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy (mean fluorescent intensity (MFI) of less than 1100 as measured in an single antigen bead (SAB) assay)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Hansa Medical AB
Study officials:
affiliation: Hansa Biopharma AB
name: Lena Winstedt, PhD
role: STUDY_DIRECTOR
References:
citation: Jordan SC, Lorant T, Choi J, Kjellman C, Winstedt L, Bengtsson M, Zhang X, Eich T, Toyoda M, Eriksson BM, Ge S, Peng A, Jarnum S, Wood KJ, Lundgren T, Wennberg L, Backman L, Larsson E, Villicana R, Kahwaji J, Louie S, Kang A, Haas M, Nast C, Vo A, Tufveson G. IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. N Engl J Med. 2017 Aug 3;377(5):442-453. doi: 10.1056/NEJMoa1612567.