TOLVAPTAN for Autosomal Recessive Polycystic Kidney Disease

Inclusion criteria

• {"criterion_text":"- Male or female subjects between 28 days and less than 18 years of age, with clinical features that are consistent with a diagnosis of ARPKD.\n- Ability for parent/legal 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. Ability to provide written informed assent from all subjects old enough per local laws to provide assent."}

Exclusion criteria

• {"criterion_text":"- Premature birth (≤ 32 weeks gestational age) for infants 28 days to < 12 weeks of age.\n- Has or at risk of having significant hypovolemia (eg, subjects that lack free access to water [inability to respond to thirst, depending on age], without adequate fluid monitoring and management) as determined by investigator.\n- Clinically significant anemia, as determined by investigator.\n- Platelets < 50000 µL.\n- Severe systolic dysfunction defined as ejection fraction < 14%.\n- Taking any other experimental medications.\n- Require ventilator support.\n- Taking medications known to induce CYP3A4.\n- Having an active infection including viral that would require therapy disruptive to IMP dosing.\n- Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.\n- Subjects with a history of substance abuse within the last 6 months (depending on age).\n- Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation.\n- Subjects who have bladder dysfunction and/or difficulty voiding.\n- Subjects taking a vasopressin agonist (eg, desmopressin).\n- Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.\n- Subjects 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).\n- Subjects who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose of IMP, during the trial (including during IMP dose interruptions), and for at least 30 days after the last dose of IMP.\n- Received or are scheduled to receive a liver transplant.\n- History of cholangitis within the last 6 months.\n- Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).\n- Evidence of syndromic conditions associated with renal cysts (other than ARPKD).\n- Abnormal liver function tests including ALT and AST, > 1.2 × ULN.\n- Has splenomegaly or portal hypertension.\n- Parents with renal cystic disease.\n- Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.\n- Cannot be monitored for fluid balance.\n- Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator."}

Primary endpoints

• {"endpoint_text":"- Safety assessments which will be summarized by descriptive statistics, and the endpoints will be • Adverse events • Vital signs • Clinical laboratory assessments","definition_or_measurement_approach":"Safety assessments summarised by descriptive statistics; endpoints listed are adverse events, vital signs and clinical laboratory assessments (as stated)."}
• {"endpoint_text":"- Serum transaminase elevations for frequency (2 ×, 3 ×, 5 × and 10 × ULN), time to onset, time to peak levels, time of offset (< 3 ×, 2 ×, or 1 × ULN), response to de challenge and re-challenge and frequency of progression to Hy’s laboratory criteria (ALT or AST > 3 × ULN and BT, > 2 × ULN without alkaline phosphatase ≥2 × ULN) • Change from baseline in sNa+","definition_or_measurement_approach":"Frequency and timing of serum transaminase elevations at specified multiples of ULN; assessment of time to onset/peak/offset, response to de-challenge and re-challenge, and progression to Hy’s criteria. Also change from baseline in serum sodium (sNa+)."}

Secondary endpoints

• {"endpoint_text":"- Annual rate of change of eGFR (eGFR Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) from baseline to post‑treatment after 18 months of treatment.","definition_or_measurement_approach":"Annual rate of change of eGFR calculated using Schwartz formula (0.413 × height [cm] / serum creatinine mg/dL) from baseline to after 18 months of treatment."}
• {"endpoint_text":"- Change from baseline of eGFR (eGFR Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) while on treatment at Months 1, 6, 12, and 18.","definition_or_measurement_approach":"Change from baseline in eGFR assessed at Months 1, 6, 12 and 18 using Schwartz formula (0.413 × height [cm] / serum creatinine mg/dL)."}
• {"endpoint_text":"- Time to RRT","definition_or_measurement_approach":"Time from baseline to initiation of renal replacement therapy (RRT)."}
• {"endpoint_text":"- Percentage of subjects who receive RRT","definition_or_measurement_approach":"Proportion of subjects who receive renal replacement therapy during the follow-up period."}
• {"endpoint_text":"- Percentage of change in kidney size of height adjusted TKV at every time point from baseline to 18 months on treatment via ultrasound using ellipsoid methodology.","definition_or_measurement_approach":"Percent change in kidney size expressed as height-adjusted total kidney volume (TKV) measured by ultrasound using ellipsoid methodology at each timepoint to 18 months."}
• {"endpoint_text":"- Change from baseline (last assessment prior to dosing) in growth percentile trajectories for height (stature), weight, and head circumference (for subjects ≤ 2 years or age) at 3 months, 6 months, 12 months, and 18 months.","definition_or_measurement_approach":"Change from last pre-dose assessment in growth percentiles for height, weight and head circumference (for subjects ≤2 years) assessed at 3, 6, 12 and 18 months."}
• {"endpoint_text":"- Age-appropriate assessment of palatability and acceptability of suspension formulation for applicable subjects.","definition_or_measurement_approach":"Age-appropriate palatability and acceptability assessments for the suspension formulation (questionnaires/assessments as applicable)."}
• {"endpoint_text":"- Proportions of each Tanner Staging by gender and age at baseline and every 6 months until Month 18/EoTx.","definition_or_measurement_approach":"Proportions by Tanner stage stratified by gender and age, assessed at baseline and every 6 months to Month 18 or end of treatment."}

Belgium

Earliest CTIS Part Ii Submission Date

29-01-2024

Latest Decision Or Authorization Date

08-05-2024

Processing Time Days

100

Number Of Sites

3

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

12

Number Of Sites

2

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

29-01-2024

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

98

Number Of Sites

2

Number Of Participants

7

Poland

Earliest CTIS Part Ii Submission Date

29-01-2024

Latest Decision Or Authorization Date

07-05-2024

Processing Time Days

99

Number Of Sites

2

Number Of Participants

1

Primary sponsor

Full Name

Otsuka Pharmaceutical Development & Commercialization Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties codes: ["1","12","5","8"]

Name

Syneos Health Inc.

Responsibilities

Site budgets and Clinical Trial Agreements

Name

IQVIA Limited

Responsibilities

Electronic Trial Master File

Third parties

• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties codes: [\"3\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"sponsorDuties codes: [\"7\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: [\"1\",\"12\",\"5\",\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Emergency Call Center\"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Aixial UK Limited","duties_or_roles":"sponsorDuties codes: [\"6\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Site budgets and Clinical Trial Agreements\"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Translation of study documents\"","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"FGK Representative Service B.V.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"EU Legal Representative\"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties codes: [\"15\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"World Courier (U.K.) Limited","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Direct to Patient IP Shipping\"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Professional Case Management Clinical Trials LLC","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Home Health Nursing support\"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Clinical Supplies Distribution\"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pro-Ficiency LLC","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Provides GCP/safety training, psiXchange training\"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Exco Intouch Limited","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"ECG storage\"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Emsere B.V.","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Ancillary Supplies- cooler bags, gels packs, urine hat\"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [\"15\",\"7\"] value: \"Patient sensor to capture vital metrics\"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Virtual visits via Telemedicine\"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc. (duplicate entry if present above)","duties_or_roles":"contact email: mpoole@endpointclinical.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [\"15\"] value: \"Electronic Trial Master File\"","organisation_type":"Pharmaceutical company"}