Clinical Trial Page

Summary
EudraCT Number:2020-004982-37
Sponsor's Protocol Code Number:NBK155/1/2020
National Competent Authority:Poland - Office for Medicinal Products
Clinical Trial Type:EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:2020-12-30
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedPoland - Office for Medicinal Products
A.2EudraCT number2020-004982-37
A.3Full title of the trial
Early rituximab treatment in children with idiopathic nephrotic syndrome Eng. ERICONS - Early RITUXIMAB in Childhood Onset Nephrotic Syndrome
Wczesne leczenie rituximabem dzieci z idiopatycznym zespołem nerczycowym Ang. ERICONS – Early RITUXIMAB in Childhood Onset Nephrotic Syndrome
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Early rituximab treatment in children with idiopathic nephrotic syndrome Eng. ERICONS - Early RITUXIMAB in Childhood Onset Nephrotic Syndrome
Wczesne leczenie rituximabem dzieci z idiopatycznym zespołem nerczycowym Ang. ERICONS – Early RITUXIMAB in Childhood Onset Nephrotic Syndrome
A.3.2Name or abbreviated title of the trial where available
ERICONS
ERICONS
A.4.1Sponsor's protocol code numberNBK155/1/2020
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorMEDICAL UNIVERSITY OF GDAŃSK
B.1.3.4CountryPoland
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportMedical Research Agency
B.4.2CountryPoland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationMEDICAL UNIVERSITY OF GDAŃSK
B.5.2Functional name of contact pointTrial coordinator - A. Żurowska
B.5.3 Address:
B.5.3.1Street Addressul. Dębinki 7
B.5.3.2Town/ cityGdańsk
B.5.3.3Post code80-211
B.5.3.4CountryPoland
B.5.6E-mailnefped@gumed.edu.pl
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name MabThera 100mg, concentrate for solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameMabThera 100mg concentrate for solution for infusion
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Yes
D.3.11.13.1Other medicinal product typeMonoclonal antibody
D.IMP: 2
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name MabThera 500mg concentrate for solution for infusion
D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
D.2.1.2Country which granted the Marketing AuthorisationGermany
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameMabThera 500mg concentrate for solution for infusion
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Yes
D.3.11.13.1Other medicinal product typeMonoclonal antibody
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboSolution for infusion
D.8.4Route of administration of the placeboIntravenous use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
NEPHROTIC SYNDROME
IDIOPATYCZNY ZESPÓŁ NERCZYCOWY
E.1.1.1Medical condition in easily understood language
NEPHROTIC SYNDROME
IDIOPATYCZNY ZESPÓŁ NERCZYCOWY
E.1.1.2Therapeutic area Diseases [C] - Symptoms and general pathology [C23]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10029164
E.1.2Term Nephrotic syndrome
E.1.2System Organ Class 10038359 - Renal and urinary disorders
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
Assessment of the duration of disease remission in the study group compared to placebo
Ocena czasu trwania remisji choroby w grupie badanej w porównaniu do placebo
E.2.2Secondary objectives of the trial
1. Assessment of treatment failure in the study group compared to placebo
2. Assessment of the total dose of steroids administered in the test group compared to placebo
3. Assessment of B-cell depletion as an indicator of the risk of recurrence in the study group compared to placebo
4. Assessment of the duration of remission in the unblinded phase of the study
5. Optimizing RTX dosing
6. Assessment of the impact of the presence of anti-RTX antibodies on the effectiveness and presence of allergic reactions
7. Assessment of the effect of hypogammaglobulinemia on the duration of remission in the study group compared to placebo
8. Understanding the risk factors for the disease and how to respond to treatment with steroid-dependent NS
1.Ocena niepowodzenia leczenia w grupie badanej w porównaniu do placebo
2.Ocena całkowitej dawki podawanych steroidów w grupie badanej w porównaniu do placebo
3.Ocena deplecji limfocytów B jako wskaźnika ryzyka nawrotu w grupie badanej w porównaniu do placebo
4.Ocena czasu trwania remisji w odślepionej fazie badania
5.Optymalizacja dawkowania RTX
6.Ocena wpływu obecności przeciwciał anty-RTX na skuteczność działania i obecność reakcji alergicznych
7.Ocena wpływu hipogammaglobulinemii na czas trwania remisji w grupie badanej w porównaniu do placebo
8.Poznanie czynników ryzyka zachorowania i sposobu reakcji na leczenie steroidozależnego ZN
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
A patient will be included in the study if he or she meets the following inclusion criteria:
1. Expresses the willingness to participate in the study and after obtaining information about the study, the patient / legal guardians will sign an informed consent form for participation in the study
2. Age at study entry> 2 years (> 24 months of age) and under 16 years of age
3. Meet the criteria for diagnosis of idiopathic steroid-dependent nephrotic syndrome (two relapses during steroid dose reduction or within two weeks of stopping steroid therapy) or nephrotic syndrome with frequent relapses (two or more relapses in 6 months on steroid therapy or four or more relapses in a period of 12 months)
4. Remission of NS immediately prior to study entry, defined as the absence or trace of protein in the urinalysis [uPCR <0.2 mg protein / mg creatinine (<20 mg protein / mmol creatinine) or <1+ in the test strip] for 3 consecutive days
5. Patients of childbearing age (conception) will commit to abstinence or to use effective contraception during the study period and up to 12 months after stopping RTX treatment; girls of childbearing potential will have a negative pregnancy test on qualifying for treatment initiation
Pacjent będzie włączony do badania, jeśli spełni następujące kryteria włączenia:
1.Wyrazi chęć udziału w badaniu i po uzyskaniu informacji na temat badania pacjent/opiekunowie prawni podpiszą formularz świadomej zgody na udział w badaniu
2.Wiek w momencie włączenia do badania > 2 lat (> 24 m.ż.) i poniżej 16 lat
3.Spełni kryteria rozpoznania idiopatycznego steroidozależnego zespołu nerczycowego (dwa nawroty podczas redukcji dawki steroidów lub w ciągu dwóch tygodni od zakończenia steroidoterapii) lub zespołu nerczycowego z częstymi nawrotami (dwa lub więcej nawrotów w ciągu 6 miesięcy na steroidoterapii albo cztery lub więcej nawrotów w okresie 12 miesięcy)
4.Remisja ZN bezpośrednio przed włączeniem do badania definiowana jako brak lub ślad białka w badaniu ogólnym moczu [uPCR < 0,2 mg białka/mg kreatyniny (< 20 mg białka/mmol kreatyniny) lub < 1+ w teście paskowym] przez 3 kolejne dni
5.Pacjenci w wieku rozrodczym (koncepcyjnym) zobowiążą się do wstrzemięźliwości seksualnej lub stosowania skutecznej antykoncepcji w okresie badania i do 12 miesięcy od zakończenia leczenia RTX; dziewczynki w wieku rozrodczym będą miały ujemny wynik testu ciążowego w momencie kwalifikacji do rozpoczęcia leczenia
E.4Principal exclusion criteria
1. Previous use of immunosuppressants such as cyclophosphamide, cyclosporin A, tacrolimus, mycophenolate mofetil, levamisole
2. Diagnosis of steroid-resistant NS, nephritic syndrome or secondary NS
3. Previous severe infection (tuberculosis, systemic mycosis), HIV, HCV, HBV infection
4. Active infection
5. Severe heart diseases (heart failure, myocardial infarction, severe heart rhythm disturbances)
6. Vaccinations with live vaccines within 4 weeks prior to study inclusion
7. Poorly controlled hypertension
8. Abnormal kidney function (eGFR <90 ml / min)
9. Autoimmune disease (IgA vasculitis, systemic lupus)
10. Current or history of cancer
11. Status after organ transplantation
12. Allergy to methylprednisolone, paracetamol, cetirizine, co-trimoxazole
13. Laboratory abnormalities: leukocyte count <3000 / µl, neutrocyte count <1500 / µl, platelet count <75,000 / µl, severe liver dysfunction: ALT or AST 2.5 times upper limit of normal
14. Prior treatment with monoclonal antibodies
15. Use of another study drug within the 6 months prior to study entry, or participation in other studies at screening
16. Severe immunodeficiency
17. Pregnancy, breastfeeding or refusal to use methods of contraception in case of the ability to become pregnant (pregnancy test required - beta hCG in the blood serum at enrollment in the study)
1. Wcześniejsze stosowanie leków immunosupresyjnych takich jak cyklofosfamid, cyklosporyna A, takrolimus, mykofenolan mofetylu, lewamizol
2.Rozpoznanie steroidoopornego ZN, zespołu nefrytycznego lub wtórnego ZN
3.Przebyta ciężka infekcja (gruźlica, grzybica układowa), zakażenie wirusem HIV, HCV, HBV
4.Aktywna infekcja
5.Ciężkie choroby serca (niewydolność serca, zawał mięśnia sercowego, ciężkie zaburzenia rytmu serca)
6.Szczepienia szczepionkami żywymi w ciągu 4 tygodni przed włączeniem do badania
7.Źle kontrolowane nadciśnienie tętnicze
8.Nieprawidłowa funkcja nerek (eGFR < 90 ml/min)
9.Choroba autoimmunologiczna (zapalenie naczyń IgA, toczeń układowy)
10.Choroba nowotworowa obecnie lub w wywiadzie
11.Stan po przeszczepieniu narządu
12.Uczulenie na metyloprednizolon, paracetamol, cetyryzynę, kotrimoksazol
13.Nieprawidłowości w badaniach laboratoryjnych: liczba leukocytów<3000/µl, liczba neutrocytów <1500/ µl, liczba płytek krwi < 75,000/µl, ciężka dysfunkcja wątroby: ALAT lub AspAT 2,5 x powyżej górnej granicy normy
14.Wcześniejsze leczenie przeciwciałami monoklonalnymi
15.Stosowanie innego badanego leku w ciągu 6 miesięcy przed włączeniem do badania lub udział w innych badaniach w momencie kwalifikacji
16.Ciężkie niedobory odporności
17.Ciąża, karmienie piersią lub odmowa stosowania metod zapobiegania ciąży w przypadku zdolności do zajścia w ciążę (wymagany test ciążowy – beta hCG w surowicy krwi przy włączaniu do badania)
E.5 End points
E.5.1Primary end point(s)
Relapse-free time (defined as proteinuria persisting> 3 days during the blinded phase (days 1 to 365)
Czas wolny od nawrotu choroby (definiowanego jako wystąpienie białkomoczu utrzymującego się > 3 dni w trakcie trwania fazy zaślepionej (od 1 do 365 dnia)
E.5.1.1Timepoint(s) of evaluation of this end point
From the time of randomization to the time of first relapse after study drug administration (1-365 days)
Od momentu randomizacji do czasu pierwszego nawrotu po podaniu leku badanego (1-365 dni)
E.5.2Secondary end point(s)
1. Total dose of steroids administered
2. Time from resolution of depletion to relapse
3. Relapse-free time during the unblinded phase (from the study drug administration to the 365 observation day)
4. a. Pharmacokinetics of RTX
b. Correlation of RTX concentration with disease relapse
c. Assessment of C4d, sC5b-9 (TCC) concentration and serum CDC activity
5. Correlation of anti-RTX antibodies with therapy failure
Correlation of the presence of anti-RTX antibodies with allergic symptoms
6. Correlation of serum immunoglobulin levels with the presence of proteinuria
Correlation of serum immunoglobulin levels with the presence of infection
7.a. Patient genotype determination (genome wide association study, GWAS)
b. Determination of the immunophenotype of patients (subpopulations of B and T lymphocytes)
c. Cytokine determination
1. Całkowita dawka podawanych steroidów
2. Czas od ustąpienia deplecji do nawrotu
3. Czas wolny od nawrotu choroby w trakcie trwania fazy odślepionej (od dnia podania leku badanego do 365 dnia obserwacji)
4. a. Farmakokinetyka RTX
b. Korelacja stężenia RTX z nawrotem choroby
c. Ocena stężenia C4d, sC5b-9 (TCC) oraz aktywności CDC surowicy
5. Korelacja obecności przeciwciał anty-RTX z niepowodzeniem terapii
Korelacja obecności przeciwciał anty-RTX z objawami alergicznymi
6. Korelacja stężenia immunoglobulin w surowicy z obecnością białkomoczu
Korelacja stężenia immunoglobulin w surowicy z obecnością zakażenia
7. a. Oznaczenie genotypu chorych (badanie asocjacyjne całego genomu, GWAS)
b. Oznaczenie immunofenotypu chorych (subpopulacji limfocytów B i T)
c. Oznaczenie cytokin
E.5.2.1Timepoint(s) of evaluation of this end point
1.12 months
2. Day 1 (before administration), 2, 8 (before administration), 9, 29, 85, 169, 365, relapse
3. From the time of study drug administration after relapse until the next relapse (1-365 days)
4.a, b. Day 1 (before and after administration), 2, 8 (before and after administration), 9, 29, 85, 169, 365, relapse
c. Day 1 (before and after administration), 2, 8 (before and after administration), 9, relapse
5. Day 1 (before and after administration), 2, 8 (before and after administration), 9, 29, 85, 169, 365, relapse
6. Day -1, 7, 29, 85, 113, 141, 169, 197, 253, 309, 365, relapse
7.a. Day 29
b. Day 1 (before administration), 2, 8 (before administration), 9, 29, 85, 169, 365, relapse
c. Day 1 (before administration), 2, 8 (before administration), 9, 29, 85, 169, 365, relapse
1. 12 miesięcy
2. Dzień 1 (przed podaniem), 2, 8 (przed podaniem), 9, 29, 85, 169, 365, nawrót
3. Od momentu podania leku badanego po nawrocie do czasu kolejnego nawrotu (1-365 dni)
4. a, b. Dzień 1 (przed i po podaniu), 2, 8 (przed i po podaniu), 9, 29, 85, 169, 365, nawrót
c. Dzień 1 (przed i po podaniu), 2, 8 (przed i po podaniu), 9, nawrót
5. Dzień 1 (przed i po podaniu), 2, 8 (przed i po podaniu), 9, 29, 85, 169, 365, nawrót
6. Dzień -1, 7, 29, 85, 113, 141, 169, 197, 253, 309, 365, nawrót
7. a. Dzień 29
b. Dzień 1 (przed podaniem), 2, 8 (przed podaniem), 9, 29, 85, 169, 365, nawrót
c. Dzień 1 (przed podaniem), 2, 8 (przed podaniem), 9, 29, 85, 169, 365, nawrót
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety No
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic Yes
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned9
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
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
LVLS
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years5
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years5
E.8.9.2In all countries concerned by the trial months0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 Yes
F.1.1Number of subjects for this age range: 60
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 60
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 60
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-12-30. Yes
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally Yes
F.3.3.6.1Details of subjects incapable of giving consent
minority
małoletność
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state60
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Further RTX treatment of patients who took part in the study will be at the discretion of the treatment center. Study drug treatment is not planned to be continued after the completion of the study.
Dalsze leczenie RTX pacjentów, którzy brali w badaniu, będzie uzależnione od decyzji ośrodka leczącego. Nie planuje się kontynuacji leczenia lekiem badanym po ukończeniu badania.
G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2021-05-19
N.Ethics Committee Opinion of the trial application
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion
P. End of Trial
P.End of Trial Status

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe