Study to Evaluate the Safety, Tolerability, Efficacy and PK of IdeS in Kidney Transplantation

A Phase II Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of Intravenous Ascending Doses of IdeS in Kidney Transplantation

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.

Study Overview

• Status: Completed
• Conditions: End Stage Kidney Disease
• Intervention / Treatment: Drug: IdeS

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 22007
    • Hansa Medical AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; IdeS as a single infusion	Drug: IdeS; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety	Adverse events, clinical laboratory tests, vital signs and ECGs	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy (mean fluorescent intensity (MFI) of less than 1100 as measured in an single antigen bead (SAB) assay)	Efficacy defined as the IdeS dosing scheme resulting in anti human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as an mean fluorescent intensity (MFI) of less than 1100 as measured in an single antigen bead (SAB) assay, within 24 hours from dosing	24 hours

Collaborators and Investigators

• Sponsor: Hansa Biopharma AB
• Collaborators: Karolinska Institutet; Uppsala University Hospital
• Investigators: Study Director: Lena Winstedt, PhD, Hansa Biopharma AB

Publications and helpful links

General Publications

• 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. Erratum In: N Engl J Med. 2017 Oct 26;377(17 ):1700.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 5, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 13-HMedIdeS-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO