Phase II Study, Evaluation of Safety and Efficacy of IdeS in Chronic Kidney Disease

NCT02224820 | Completed Phase 2 Results DMC

• 2 other identifiers: 13-HMedIdeS-022013-005417-13
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

IdeS is an immunoglobulin g (IgG) cleaving enzyme. It will given to patients with donor specific antibodies to reduce the antibody load and thus enable kidney transplantation. IdeS antibody reducing efficacy and its safety will be studied.

Conditions

Chronic Kidney Disease

Keywords

transplantation; sensitised patients; HLA-antibodies

Outcome Measures

Primary Outcomes (1)

• Efficacy

  Efficacy was defined as the IdeS dosing scheme in the majority of the patients resulting in human leucocyte antigen (HLA) antibody levels which are acceptable for transplantation, measured as mean fluorescent intensity (MFI) of less than 1100, within 24 hours from dosing. MFI was determined by single antigen bead (SAB) assay and detection of complement fixating ability (CIq Screen) in serum.

  24 hours

Secondary Outcomes (4)

• Safety

  9 weeks

• Pharmacodynamics

  Up to day 64

• Immunogenicity

  Up to 64 days

• Pharmacokinetics

  Up to 21 days

Study Arms (1)

Intravenous IdeS

EXPERIMENTAL

One or two doses of IdeS in ascending doses

Biological: IdeS

Interventions

IdeS BIOLOGICAL

Doses are administered in ascending doses

Intravenous IdeS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with chronic kidney disease and in dialysis with identified antibodies against at least two HLA antigens of which at least one is 3000 MFI or more as measured by SAB assay on at least two occasions.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (1)

Dept. of Transplant Surgery, Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (3)

• Bockermann R, Jarnum S, Runstrom A, Lorant T, Winstedt L, Palmqvist N, Kjellman C. Imlifidase-generated Single-cleaved IgG: Implications for Transplantation. Transplantation. 2022 Jul 1;106(7):1485-1496. doi: 10.1097/TP.0000000000004031. Epub 2021 Dec 27.

  PMID: 34966107 DERIVED

• Lorant T, Bengtsson M, Eich T, Eriksson BM, Winstedt L, Jarnum S, Stenberg Y, Robertson AK, Mosen K, Bjorck L, Backman L, Larsson E, Wood K, Tufveson G, Kjellman C. Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients. Am J Transplant. 2018 Nov;18(11):2752-2762. doi: 10.1111/ajt.14733. Epub 2018 Apr 17.

  PMID: 29561066 DERIVED

• 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.

  PMID: 28767349 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Tomas Lorant
• Organization: Dept of Transplant Surgery, Uppsala University Hospital

tomas.lorant@surgsci.uu.se

+46 70 677 29 01

Study Officials

• Tomas Lorant, MD, PhD

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 25, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 3, 2017
• Results First Posted: May 23, 2016

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)