E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
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E.1.1.1 | Medical condition in easily understood language |
Genetic disorder that causes numerous cysts to grow in the kidneys. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036047 |
E.1.2 | Term | Polycystic kidney, autosomal recessive |
E.1.2 | System Organ Class | 100000004850 |
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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 evaluate the effect of tolvaptan on the need for RRT in pediatric subjects with ARPKD
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E.2.2 | Secondary objectives of the trial |
Evaluate changes in eGFR and palatability and acceptability of formulation
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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 |
Further research will be conducted on the remainder of the samples that are collected during the trial to understand the genetics of ARPKD |
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E.3 | Principal inclusion criteria |
1. Male or female subjects between 28 days and < 12 weeks of age, inclusive. 2. Must have clinical and imaging features that are consistent with a diagnosis of ARPKD with all the following characteristics: - Nephromegaly (> 2 standard deviations from age appropriate standard via ultrasound) - Multiple renal cysts - History of oligohydramnios or anhydramnios 3. Ability for parent or guardian to provide written, informed consent prior to initiation of any trial related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial.
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E.4 | Principal exclusion criteria |
1. Premature birth (≤ 32 weeks gestational age) 2. Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration, or history of kidney transplantation 3. Evidence of syndromic conditions associated with renal cysts (other than ARPKD) 4. Abnormal liver function tests including ALT and AST, > 1.2 × ULN 5. Parents with renal cystic disease 6. Receiving chronic diuretic that could not be adjusted after tolvaptan initiation 7. Cannot be monitored for fluid balance 8. Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator 9. Has or at risk of having significant hypovolemia (eg, subjects that lack free access to water, without adequate fluid monitoring and management) as determined by investigator 10. Clinically significant anemia, as determined by investigator 11. Severe systolic dysfunction defined as ejection fraction < 14% 12. Serum sodium levels < 130 mmol/L or >145 mmol/L (or the ULN of the local laboratory, whichever is lower). 13. Taking any other experimental medications 14. Require ventilator support 15. Taking medications known to induce CYP3A4 16. Having an infection including viral that would require therapy disruptive to IMP dosing 17. Platelet count <50,000 µL 18. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia). 19. Bladder dysfunction and/or difficulty voiding 20. Taking a vasopressin agonist (eg, desmopressin) 21. Having concomitant illnesses or taking medications likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin) 22. History of cholangitis 23. Received or are scheduled to receive a liver transplant
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of subjects having RRT by 1 year of age
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Rate of change of eGFR (eGFR Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) from pretreatment to post-treatment after 2 years of treatment - Age-appropriate assessment of acceptability and palatability of formulation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
pre-treatment to post treatment after 2 years of treatment |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Canada |
United States |
France |
Poland |
Spain |
Czechia |
Germany |
Italy |
Belgium |
United Kingdom |
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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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Expected trial participation duration for each subject to be approximately 2 years with the option to continue to receive tolvaptan treatment for 12 additional months |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |