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

NCT ID: NCT02790437

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2018-07-03

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.

Conditions

Kidney Failure, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment IdeS

IdeS intravenous infusion

Group Type: EXPERIMENTAL

IdeS

Intervention Type: DRUG

One dose of 0.25 mg/kg BW IdeS on study day 0. If negative crossmatch is not achieved, a second dose can be given within 2 days of the first infusion.

Kidney transplantation

Intervention Type: PROCEDURE

Performed following IdeS treatment

Interventions

IdeS

One dose of 0.25 mg/kg BW IdeS on study day 0. If negative crossmatch is not achieved, a second dose can be given within 2 days of the first infusion.

Intervention Type: DRUG

Kidney transplantation

Performed following IdeS treatment

Intervention Type: PROCEDURE

Other Intervention Names

IgG endopeptidase

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hansa Biopharma AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lena Winstedt, PhD

Role: STUDY_DIRECTOR

Hansa Biopharma AB

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

New York University School of Medicine

New York, New York, United States

Necker Hospital

Paris, , France

Uppsala University Hospital

Uppsala, , Sweden

Countries

United States; France; Sweden

References

Jaffe IS, Runstrom A, Tatapudi VS, Weldon EP, Deterville CL, Dieter RA, Montgomery RA, Lonze BE, Mangiola M. Clinical Outcomes and Donor-specific Antibody Rebound 5 y After Kidney Transplant Enabled by Imlifidase Desensitization. Transplant Direct. 2025 Jan 9;11(2):e1752. doi: 10.1097/TXD.0000000000001752. eCollection 2025 Feb.

Reference Type: DERIVED

PMID: 39802198 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34236770 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33093408 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

15-HMedIdeS-06

Identifier Type: -

Identifier Source: org_study_id