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

Primary Purpose

Chronic Kidney Disease

Status

Completed

Phase

Phase 2

Locations

Sweden

Study Type

Interventional

Intervention

IdeS

About this trial

This is an interventional treatment trial for Chronic Kidney Disease focused on measuring transplantation, sensitised patients, HLA-antibodies

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

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

Sites / Locations

Dept. of Transplant Surgery, Uppsala University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intravenous IdeS

Arm Description

One or two doses of IdeS in ascending doses

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Safety

Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)

Pharmacodynamics

IgG cleavage and regeneration measured by ELISA

Immunogenicity

Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period

Pharmacokinetics

IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.

Full Information

NCT ID

NCT02224820

First Posted

August 15, 2014

Last Updated

January 18, 2017

Sponsor

Hansa Biopharma AB

1. Study Identification

Unique Protocol Identification Number

NCT02224820

Brief Title

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

Official Title

A Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous IdeS After Administration of Ascending Doses in Chronic Kidney Disease Patients

Study Type

Interventional

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

June 2014 (undefined)

Primary Completion Date

February 2015 (Actual)

Study Completion Date

February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hansa Biopharma AB

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

Study 13-HMedIdeS-02 (EudraCT no. 2013-005417-13) is a single centre, single arm, dose finding, Phase II study in sensitized CKD patients assessing safety, tolerability, pharmacokinetics (PK) and efficacy of HMED-IdeS without intent to transplantation. However, patients are not removed from the transplant waitlist during the study. Included patients has a panel reactive antibody [PRA] >70% (n=7).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease

Keywords

transplantation, sensitised patients, HLA-antibodies

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intravenous IdeS

Arm Type

Experimental

Arm Description

One or two doses of IdeS in ascending doses

Intervention Type

Biological

Intervention Name(s)

IdeS

Intervention Description

Doses are administered in ascending doses

Primary Outcome Measure Information:

Title

Efficacy

Description

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Safety

Description

Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs)

Time Frame

9 weeks

Title

Pharmacodynamics

Description

IgG cleavage and regeneration measured by ELISA

Time Frame

Up to day 64

Title

Immunogenicity

Description

Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period

Time Frame

Up to 64 days

Title

Pharmacokinetics

Description

IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded.

Time Frame

Up to 21 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tomas Lorant, MD, PhD

Organizational Affiliation

Uppsala University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dept. of Transplant Surgery, Uppsala University Hospital

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34966107

Citation

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.

Results Reference

derived

PubMed Identifier

29561066

Citation

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.

Results Reference

derived

PubMed Identifier

28767349

Citation

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.

Results Reference

derived

Learn more about this trial

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

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