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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005417-13 | EudraCT Number |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intravenous IdeS | Experimental | One or two doses of IdeS in ascending doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IdeS | Biological | Doses are administered in ascending doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety | Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs) | 9 weeks |
| Pharmacodynamics | IgG cleavage and regeneration measured by ELISA |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tomas Lorant, MD, PhD | Uppsala University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dept. of Transplant Surgery, Uppsala University Hospital | Uppsala | 75185 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34966107 | Derived | 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. | |
| 29561066 | 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. |
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In total, 10 patients were assessed for eligibility. One patient declined to participate and one patient was not available for recieving information about the study. Eight patients were enrolled and started treatment.
The study was performed at a medical clinic, the Department of Transplantat Surgery, Uppsala, SE between 10 Jun 2014 and 13 Feb 2015. The patients had chronic kidney disease, were in dialysis and on the waiting list for transplantation. (Transplantation was not part of the protocol).
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| ID | Title | Description |
|---|---|---|
| FG000 | Intravenous IdeS | One or two doses of IdeS in ascending doses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
0ne patient interrupted treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Intravenous IdeS | One or two doses of IdeS in ascending doses IdeS |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Inter-Quartile Range | MFI | 24 hours |
|
|
From the time of admission until last visit, 64 days after treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intravenous IdeS | One or two doses of IdeS in ascending doses. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Tomas Lorant | Dept of Transplant Surgery, Uppsala University Hospital | +46 70 677 29 01 | tomas.lorant@surgsci.uu.se |
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| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| Up to day 64 |
| Immunogenicity | Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period | Up to 64 days |
| Pharmacokinetics | IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded. | Up to 21 days |
| 28767349 | 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. |
| years |
|
| Gender | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weight (kg) | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/mg^2 |
|
| Height | Mean | Standard Deviation | cm |
|
|
|
| Secondary | Safety | Adverse events (all clinical laboratory tests, vital signs and ECG jugded as clinically significant were reported as AEs) | Posted | Number | Adverse events | 9 weeks |
|
|
|
| Secondary | Pharmacodynamics | IgG cleavage and regeneration measured by ELISA | Posted | Mean | Standard Deviation | µg/mL | Up to day 64 |
|
|
|
| Secondary | Immunogenicity | Presence of Anti-Drug Antibodies formation in serum throughout a 64 day period | Posted | Number | participants | Up to 64 days |
|
|
|
| Secondary | Pharmacokinetics | IdeS T1/2 in alpha phase. One patient who interrupted dose was excluded. | Posted | Mean | Inter-Quartile Range | h | Up to 21 days |
|
|
|
| 4 |
| 8 |
| 8 |
| 8 |
| Suspected upper respiratory infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Increased mucos production | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Clostridium difficile infection | Infections and infestations | MedDRA (18.6) | Systematic Assessment |
|
| Herpes simplex infection | Infections and infestations | MedDRA (18.6) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (18.6) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (18.6) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (18.6) | Systematic Assessment |
|
| Alanine aminotransferas increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Aspartate aminotransferas increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Blood phosphorus increased | Investigations | MedDRA (18.6) | Systematic Assessment |
|
| C-reactive proteine increased | Investigations | MedDRA (18.6) | Systematic Assessment |
|
| Donor specific antibody present | Investigations | MedDRA (18.6) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (18.6) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dyspesia | Gastrointestinal disorders | MedDRA (18.6) | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (18.6) | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (18.6) | Systematic Assessment |
|
| Leucocytosis | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Leucopenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (18.6) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dysgeuisa | Nervous system disorders | MedDRA (18.6) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (18.6) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (18.6) | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA (18.6) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (18.6) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
|
| Scleral haemorrage | Eye disorders | MedDRA (10.0) | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (18.6) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (18.6) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Kidney transplant rejection | Immune system disorders | MedDRA (10.0) | Systematic Assessment | Dose was interrupted for this patient due to infusion reaction.The pat was transplanted (not defined as SAE in protocol) 4 days after dosing. Pat remained in the study for safety follow-up. A number of AEs related to the transplantation are reported. |
|
| Haematuria | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |