E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Idiopathic Nephrotic Syndrome |
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E.1.1.1 | Medical condition in easily understood language |
Adults with biopsy proven idiopathic Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS) currently in remission but requiring reduction or cessation of immunosuppressive therapy. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
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 |
1) VPA (Valproic acid) on top of or in substitution of standard of care agents is effective in remission induction in patients with FSGS or MCD with proteinuria resistant to first line therapy with corticosteroids.
2) VPA is effective in remission maintenance allowing reduction and cessation of chronic immunosuppression without relapse in patients with frequently relapsing FSGS or MCD.
This is an exploratory pilot study with two different sub-cohorts of patients which have different endpoints. |
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E.2.2 | Secondary objectives of the trial |
Determine the disease response by the proportion of subjects with partial remission
Determine the extent to which standard immunosuppression can be reduced
Evaluate the evolution of renal function estimated by MDRD-GFR
Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
18 years and older
Able to give informed consent
Biopsy proven idiopathic FSGS or MCD
For remission induction (currently induction therapy):
• Proteinuria >1g/g creatinine
• Subjects received high dose prednisone (1mg/kg-maximum 80mg prednisone-equivalent) according to guidelines or present relative contraindications or intoler-ance to high-dose corticosteroids during induction.
For remission maintenance (currently in remission):
• At least one relaps
• Requiring reduction or cessation of current maintenance immunosuppressive therapy required to maintain remission.
Organ function:
• Bilirubin/AST/ALT< 2 ULN
• PLT>100.000 10*6/L
• INR1.5 except if on anti-vitamin K treatment
• Lipase <1.5 ULN
• Creatinine clearance >30ml/min
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E.4 | Principal exclusion criteria |
Patients younger than 18 years
Unable to give informed consent
Contraindication for VPA*
Secondary etiologies for FSGS or MCD**
Multiple organ transplantation
Currently participating in another clinical trial
Pregnant or lactating women
Women unwilling to take efficient contraceptive measures for the duration of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in remission induction is the proportion of patients in complete remission. Complete remission is defined as a reduction of proteinuria to <300mg/g creatinine or < 0.3g/d and normal serum creatinine (or stable creatinine if baseline creatinine before disease onset is well documented) and serum albumin > 3.5g/dL.
The primary endpoint in remission maintenance is the proportion of patients able to reduce maintenance immunosuppression to a monotherapy of 4 mg methylprednisolone or less while remaining in complete remission as defined above.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For both groups, 6 months after inclusion |
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E.5.2 | Secondary end point(s) |
Remission induction:
1) The proportion of subjects with partial remission defined as a reduction in proteinuria to 0.3-3.5g/d or 300-3500mg/g creatinine and a decrease of at least 50% from baseline proteinuria and stable serum creatinine (change in creatinine < 25%).
2) The percent change in proteinuria.
3) The proportion of patients attaining full or partial remission with 4mg methylprednisolone or less.
4) Evolution of renal function estimated by CKD-EPI.
Remission maintenance:
1) The proportion of patients remaining in remission after reduction of maintenance immunosuppression to monotherapy with 4 mg of methylprednisolone or less.
2) The percent reduction in the dosage of immunosuppression in patients who remain in remission.
3) The proportion of patients with relapse (defined as proteinuria > 3.5g/d or >3500mg/g) after minimization or cessation of immunosuppression on VPA.
4) Evolution of renal function estimated by CKD-EPI.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Remission induction:
1) The proportion of subjects with partial remission at 6 months
2) The percent change in proteinuria at 6 months
3) The proportion of patients attaining full or partial remission with 4mg methylprednisolone or less at 6 months and 12 months
4) Evolution of renal function at 6 and 12 months
Remission maintenance:
1) the proportion of patients remaining in remission for at least 6 months after reduction of maintenance immunosuppression
2) The percent reduction in the dosage of immunosuppression in patients who remain in remission at 6 and 12 months
3) The proportion of patients with relapse after minimization or cessation of immunosuppression on VPA at 6 and 12 months
4) Evolution of renal function at 6 and 12 months
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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) | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
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 | 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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |