A Phase II Study to Evaluate the Efficacy of IdeS to Desensitize Transplant Patients With a Positive Crossmatch Test

A Phase II Study to Evaluate the Efficacy of IdeS (IgG Endopeptidase) to Desensitize Transplant Patients With a Positive Crossmatch Test

The purpose of this study is to evaluate the effectiveness of the study drug IdeS in patients who are on the waiting list for kidney transplant and have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. At study entry, the patients will have an available deceased or live donor with a positive crossmatch test. The study will assess IdeS efficacy and safety in removing Donor Specific Antibodies (DSAs) and thereby convert a positive crossmatch test to negative.

The study will assess the IdeS efficacy in creating a negative crossmatch test (XM) in patients who exhibit donor specific antibodies (DSA) and have a positive crossmatch test to their available live or deceased donors. The first 3 patients in this study will receive a kidney from a deceased donor. The study will primarily examine the efficacy of IdeS in creating a negative XM. The first 3 patients will receive one dose of 0.25 mg/kg BW IdeS on study day 0. If it is considered safe and negative crossmatch test is not achieved after the first dose, an additional IdeS infusion can be given within 2 days of the first infusion. The dose schedule may be increased to 0.5 mg/kg BW given once or twice after the first 3 patients have been tested. The decision to escalate the dose will be done after evaluation of safety and efficacy.

Inclusion Criteria:

• Patients on the kidney transplant waitlist who have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. The breadth and strength of sensitization will predict an extremely low likelihood of successful desensitization or kidney paired donation.
• Patients with a live or deceased donor with a positive crossmatch test.

Exclusion Criteria:

• Previous treatment with IdeS
• Previous high dose IVIg treatment (2 g/kg BW) within 28 days prior to IdeS treatment
• Lactating or pregnant females
• Women of child-bearing age who are not willing or able to practice FDA-approved forms of contraception
• HIV-positive patients
• Patients with clinical signs of HBV or HCV infection
• Patients with active tuberculosis
• A significantly abnormal general serum screening lab result according to the investigator's judgement. Hgb cannot be < 6.0 g/dL
• Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure > NYHA (New York Heart Association) grade 3, unstable coronary disease or oxygen dependent COPD
• Individuals deemed unable to comply with the protocol
• Patients with clinical signs of CMV or EBV infection
• Patients with a history of major thrombotic events, patients with active peripheral vascular disease or patients with proven hypercoagulable conditions
• Patients should not have received investigational drugs within 4 half-lives (or similar)
• Known allergy/sensitivity to IdeS infusions
• Patients who have a live donor and test positive for ImmunoCap anti-IdeS IgE