Clinical trial NCT02790437: A Phase II Study to Evaluate the Efficacy of IdeS to Desensitize Transplant Patients With a Positive Crossmatch Test
Official title: A Phase II Study to Evaluate the Efficacy of IdeS (IgG Endopeptidase) to Desensitize Transplant Patients With a Positive Crossmatch Test
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Failure, Chronic
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
First posted: 2016-06-03
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Crossmatch Conversion (Positive to Negative)
timeFrame: Within 24 hours of IdeS dosing
Secondary outcomes:
measure: Number of Patients With Donor Specific Antibodies With an MFI Value >3000
timeFrame: Within 180 days after administration of IdeS.
measure: Time to Create a Negative CDC Crossmatch Test
timeFrame: 2h, 6h, 24h after administration of IdeS.
measure: Time to Create a Negative FACS Crossmatch Test
timeFrame: 2h, 6h, and 24h after administration of IdeS
measure: Kidney Function After IdeS Treatment Assessed by eGFR
timeFrame: Within 180 days after administration of IdeS
measure: Serum IgG Concentration After Administration of IdeS
timeFrame: Within 180 days after administration of IdeS.
measure: Pharmacokinetics - Cmax (First Dose)
timeFrame: Pre-dose to Day 14 after administration of IdeS.
measure: Pharmacokinetics - Cmax (Second Dose)
timeFrame: Pre-dose until Day 14 after administration of IdeS
measure: Pharmacokinetics - Tmax (First Dose)
timeFrame: Pre-dose to Day 14 after administration of IdeS
measure: Pharmacokinetics - Tmax (Second Dose)
timeFrame: Pre-dose to Day 14 after administration of IdeS
measure: Pharmacokinetics - AUC
timeFrame: Pre-dose to Day 14 after administration of IdeS.
measure: Pharmacokinetics - t1/2
timeFrame: Pre-dose to Day 14 after administration of IdeS.
measure: Pharmacokinetics - CL
timeFrame: Pre-dose to Day 14
measure: Pharmacokinetics - Vss
timeFrame: Pre-dose to Day 14 after administration of IdeS
measure: Pharmacokinetics - Vz
timeFrame: Pre-dose to Day 14 after administration of IdeS.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Paris
country: France
facility: Necker Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Hansa Biopharma AB
name: Lena Winstedt, PhD
role: STUDY_DIRECTOR
References:
citation: Kjellman C, Maldonado AQ, Sjoholm K, Lonze BE, Montgomery RA, Runstrom A, Lorant T, Desai NM, Legendre C, Lundgren T, von Zur Muhlen B, Vo AA, Olsson H, Jordan SC. Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients. Am J Transplant. 2021 Dec;21(12):3907-3918. doi: 10.1111/ajt.16754. Epub 2021 Jul 19.
citation: Jordan SC, Legendre C, Desai NM, Lorant T, Bengtsson M, Lonze BE, Vo AA, Runstrom A, Laxmyr L, Sjoholm K, Schiott A, Sonesson E, Wood K, Winstedt L, Kjellman C, Montgomery RA. Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes). Transplantation. 2021 Aug 1;105(8):1808-1817. doi: 10.1097/TP.0000000000003496.