E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic nephrotic syndrome
Focal segmental glomerulosclerosis
Minimal change disease
|
|
E.1.1.1 | Medical condition in easily understood language |
Nephrotic syndrome of unkown cause
Focal segmental glomerulosclerosis
Minimal change disease |
|
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 |
To evalute the efficacy of rituximab in comparison to continued corticosteroid treatment in ipatients with diopathic nephrotic syndrome unresponsive to 8 weeks of high dose prednisone. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the proportion of patients with partial and late remissions
2. To evaluate time to remission
3. To evaluate the proportion of patients with a relapse and difference in time to relapse
4. To evalauta the Quality of life measured by RAND-36 and TNO-AZL Questionnaire for Adult's Health-Related Quality of Life for people of 16 years
and older (TAAQOL).
5. To evaluate the number and proportion of patients with side effects
6, To determine the cost-effectiveness and cost-utility
7. To evaluate differences in kidney function
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 18 years
Persistent proteinuria ≥ 2 g/ 24 hours or a protein-to-creatinine ratio ≥ 2 g/10mmol (2 g/g) after 8 weeks of treatment with high dose prednisone 1 mg/kg/day (max 80 mg/day)
Idiopathic nephrotic syndrome caused by biopsy proven minimal change disease or focal segmental glomerulosclerosis |
|
E.4 | Principal exclusion criteria |
• Severe nephrotic syndrome with hypotension
• Previous treatment with immunosuppressive medication other than prednisone
• Treatment with prednisone > 10 weeks in last six months
• Secondary form of FSGS or minimal change disease
• Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(anti-HBc).
• Patients infected with HIV or suffering from other active infections
• Patients inoculated with a live vaccine within 4 weeks prior to inclusion
• Pregnancy, breast feeding, women with inadequate contraception
• Malignancy
• Kidney transplantation
• Previous treatment with monoclonal antibodies |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients reaching complete remission |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Proportion of patients with a partial remission
2. Proportion of patients with a late remission (partial and complete)
3. Time to first remission (partial and complete) and time to relapse
4. Proportion of patients with a relapse
5. Need for immunosuppressive therapy other than assigned treatment with rituximab or prednisolone
6. Difference in quality of life measured by RAND-36 and TNO-AZL Questionnaire for Adult's Health-Related Quality of Life for people of 16 years and
older (TAAQOL)
7. Proportion of patients with adverse events graded according to NCI-CTCAE v4.03
8. Cost-effectiveness analysis and cost -utility analysis
9. Difference in creatinine clearance and estimated glomerular filtration rate
10. Proportion of patients with an increase of serum creatinine > 50% |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
ad1. 2 months
ad2. 2-12 months
ad 3. 12 months
ad 4. 12 months
ad 5. 2 and12 months
ad 6. 2 and 12 months
ad 7. 2 and 12 months
ad 8. 2 and 12 months
ad9. 2 and 12 months
ad 10. 2 and 12 months |
|
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 | No |
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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
Last visit of the last subject included in the trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |