E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic nephrotic syndrome in childhood |
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E.1.1.1 | Medical condition in easily understood language |
nephrotic Syndrome in childhood |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029164 |
E.1.2 | Term | Nephrotic syndrome |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main purpose of the study is to show that MMF in the initial treatment of SSNS in children is not inferior regarding maintenance of initial remission and subsequent relapse rate compared to the standard high-dose prednisone regimen |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints are divided into five items:
1.Course of the disease as described by the following criteria
a.Time from remission to first relapse
b.Number of relapses during follow-up
c.Mean relapse rate per patient and year
d.Number of frequent relapsers
e.Time from remission to intensification of immunosuppressive treatment with other drugs due to glucocorticoid-induced toxicity
f.Rate of patients who require more intense immunosuppressive treatment
2.Glucocorticoid-associated toxicity
3.Mycophenolate mofetil-associated toxicity
4.Health-related quality of life,
5.Days missing school attendance and days of hospitalization |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Measurement of Inosine-5'-monophosphate dehydrogenase (IMPDH) activity in pediatric patients with steroid-sensitive nephrotic syndrome under therapy with mycophenolate mofetil
Version and date: Version 1.0, 21.07.2016
Objective: measurement of IMPDH activity |
Titel: Messung der Inosin 5´-Monophosphat-Dehydrogenase (IMPDH) Aktivität bei pädiatrischen Patienten mit einem steroidsensiblen nephrotischen Syndrom unter Mycophenolatmofetil-Therapie
Version und Datum: Version 1.0, 21.07.2016
Ziele: Messung der IMPDH Aktivität. Im einzelnen: Ist das Ansprechen
auf die Therapie mit MPA abhängig von der basalen IMPDH-Aktivität vor Therapie? Ist das Ansprechen auf die Therapie mit MPA abhängig von der maximalen IMPDH-Aktivitäts-Hemmung? Ist die Hemmung der IMPDH-Aktivität abhängig von der Konzentration der freien MPA und/ oder der Gesamt-MPA? |
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E.3 | Principal inclusion criteria |
Subjects meeting all of the following criteria will be considered for admission to the study:
-First episode of steroid-sensitive nephrotic syndrome (SSNS)
-in remission induced by daily glucocorticoids
-male and female children aged ≥ 1 year and ≤ 10 years at beginning of study (typical age range of patients with SSNS
-Ability of the persons having care and custody of the child to understand character and individual consequences of clinical study
-Written informed consent of the persons having care and custody of the child (must be available before enrolment in the study)
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following criteria will not be included in the study:
-Secondary nephrotic syndrome
-estimated glomerular filtration rate (eGFR) <90 ml/min x 1.73 m2 BSA
-Ongoing treatment with systematically administered glucocorticoids or other immunosuppressive drugs at time of first episode of nephrotic syndrome.
• Hemoglobin concentration of ≤9 g/dL
• Leucocyte count of ≤2.500/µl
Refusal of subject (please see also chapter 10.5)•
Severe chronic gastrointestinal disease
-History of hypersensitivity to mycophenolate mofetil or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of suspension of mycophenolate mofetil (CellCept suspensionīĸ)
-Participation in other clinical studies or observation period of competing studies, respectively.
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E.5 End points |
E.5.1 | Primary end point(s) |
Occurence of treated relapse within 24 months after end of Initial treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 8, 27 month after day 1. |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint(s):
• Course of the disease: Time from remission to first relapse; number of relapses; mean relapse rate per patient and year; incidence of frequent relapsers
• Prednisone-associated toxicity: Cumulative prednisone dose (mg/m² BSA); body mass index (standard deviation score); striae; hypertrichosis; acne; arterial hypertension; disturbances of carbohydrate and lipid metabolism; growth failure; cataract; glaucoma; psychological disturbances
• MMF-associated toxicity: diarrhea; blood cell count disturbances, infections
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 34 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 10 |