E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Kidney Disease with donor specific antibodies (ASA) |
Kronisk njursvikt med donator specifika antikroppar |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney Disease with antibodies to donated organ |
Kronisk njursvikt med antikroppar mot donerat organ |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To asses the IdeS efficacy in creating a negative crossmatch test |
Att utvärdera IdeS förmåga att skapa negativ korstest |
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E.2.2 | Secondary objectives of the trial |
To determine DSA levels at multiple times To determine time to creating a negative CDC crossmatch test To determine time to creating a negative FACS crossmatch test To evaluate safety parameters To monitor kidney function after IdeS treatment To establish the pharmacokinetic (PK) profile of IdeS To establish the pharmacodynamic (PD) profile of IdeS To establish the immunogenicity profile (ADA) of IdeS |
Att bestämma DSA vid flera tidpunkter Att bestämma tid för att skapa negativ CDC korstest Att bestämma tid för att skapa negativ FACS korstest Att utvärdera säkerhetsvariabler Att följa njurfunktionen Att etablera farmakokinetisk (PK) profil för IdeS Att etablera farmakodynamisk (PD) profil för IdeS Att etablera immugnicitet (ADA) för IdeS |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female age 18-70 years at the time of screening Patients on the kidney transplant waitlist who have previously undergone desensitization unsuccessfully or in whom effective desensitization will be highly unlikely. Patients with a live or deceased donor with a positive crossmatch test. Patient must be able to understand and sign the informed consent
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Män eller kvinnor mellan 18-70 år Patienter som är på väntelista för transplantation och som tidigare har genomgått desensitisering som misslyckades eller är det inte troligt att desensitisering skulle lyckas Patienter som har en levande eller avliden donator och positiv korstest Patienter som har förstått och signerat informerat samtycke
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E.4 | Principal 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 HBV infection or HCV infection Patients with active tuberculosis A significantly abnormal general serum screening lab result according to the investigator’s judgement. Severe other conditions requiring treatment and close monitoring, e.g. cardiac failure, unstable coronary disease or oxygen dependent COPD Patients with active CMV or EBV infection Patients with a history of major thrombotic events, patients with active peripheral vascular disease or patients with proven hypercoagulable conditions Allergy/sensivity to IdeS infusions Patients who have a live donor and test positive for ImmunoCAP anti-IdeS IgE
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Tidigare behandling med IdeS Tidigare behandlats med högdos IVIg inom 28 dagar före IdeS behandling Kvinnor i fertil ålder som är gravida, ammar eller planerar att bli gravida. Bara kvinnor som använder två tillförlitliga preventivmedel kan delta HIV-positiva patienter Patienter med HBV infektion eller HCV infektion Patienter med tuberkolos Patienter med aktiv CMV eller EBV infektion Kliniskt signifikant onormalt labstatus på screeningbesöket enligt prövarens bedömning Annan allvarlig sjukdom som kräver monitorering exempelvis hjärtsvikt, instabil hjärtsjukdom eller KOL Patienter med en historia av svåra trombotiska händelser, patienter med aktiv perifer vaskulär sjukdom eller patienter med påvisade hyperkoagulerbara tillstånd Allergi/överkänslighet mot IdeS infusion Patienter som har en levande donator och är testad positiv för ImmunoCAP anti-IdeS IgE
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy defined as IdeS ability to create a negative crossmatch test within 24 hours after IdeS dosing |
Effekt definierad som IdeS förmåga att skapa negativ korstest inom 24 timmar efter given Ides dos |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 24 hours after IdeS dosing |
Inom 24 timmar efter given IdeS dos |
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E.5.2 | Secondary end point(s) |
DSA levels at pre-dose and 2, 6, 24 and 48 hours and days 7, 14, 21, 28, 64, 90, 120 and 180 post IdeS treatment Time to creating a negative CDC crossmatch test Time to creating a negative FACS crossmatch test Safety parameters (adverse events, clinical laboratory tests, vital signs and ECGs) Kidney function after IdeS treatment assessed by, filtration (eGFR), creatinine and proteinuria up to 180 days post treatment Pharmacokinetic (PK) profile of IdeS up to day 14 Pharmacodynamic (PD) profile of IdeS (cleavage and recovery of IgG) up to day 180 post IdeS Immunogenicity profile of IdeS by measuring anti-drug antibodies (ADA)
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DSA pre-dos och 2, 6, 24 och 48 tim och dag 7, 14, 21, 28, 64, 90, 120 och 180 efter IdeS behandling Tid att skapa negativ CDC korstest Tid att skapa negativ FACS korstest Säkerhetsvariabler såsom biverkningar, labprover, puls blodtryck,temperatur och Ekg Njurfunktion efter behandling evaluerad genom filtration (eGFR), kreatinin and proteinuri fram till 180 dagar efter behandling
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DSA levels at pre-dose and 2, 6, 24 and 48 hours and days 7, 14, 21, 28, 64, 90, 120 and 180 post IdeS treatment Safety parameters at 2, 6, 24 and 48 hours and days 3, 7, 9, 14, 21, 28, 64, 90, 120 and 180 post IdeS treatment Kidney function at 24 and 48 hours and days 3, 7, 9, 14, 21, 28, 64, 90, 120 and 180 post IdeS treatment
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DSA pre-dos och 2, 6, 24 och 48 timmar och på dag 7, 14, 21, 28, 64, 90, 120 och 180 efter IdeS behandling Säkerhetsvariabler 2, 6, 24 och 48 timmar och på dag 3, 7, 9, 14, 21, 28, 64, 90, 120 och 180 efter IdeS behandling Njurfunktion 24 och 48 tim och på dag 3, 7, 9, 14, 21, 28, 64, 90, 120 och 180 dagar efter IdeS behandling
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogenicitet |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |