An Open-label, Phase 2 Pilot Study on the Efficacy and Safety of Piclidenoson in Patients With Lowe Syndrome

Objectives

• Primary Objective:

• The primary objective of the study is to test the efficacy of piclidenoson to increase renal uptake of 99mTc-labeled DMSA after 6 months (26 weeks) of treatment as a measure the reabsorption capacity of LMWPs by renal proximal tubules.
• Secondary Objectives of the study are:

• to evaluate changes in urinary excretion of LMWPs and other clinical parameters of renal Fanconi syndrome,
• to evaluate the safety of piclidenoson in patients with Lowe syndrome.

Primary Endpoint

• Improvement in the renal uptake, as compared to Baseline, of 99mTc-DMSA after 6 months (26 weeks) of treatment with piclidenoson (a p-value of ≤ 0.05 will be used to determine statistical significance), as a measure of the reabsorption capacity of LMWPs by renal proximal tubules.

Secondary Endpoints

• Improvement of LMW proteinuria as assessed by changes urinary excretion of retinol-binding protein and beta-2 microglobulin, as compared to baseline, after 3 and 6 months of treatment (a p-value of ≤ 0.05 will be used to determine statistical significance).
• Improvement of Fanconi syndrome as assessed by 24-hour urine volume; urinary excretion of sodium, glucose, phosphate, and amino acids; and changes in serum bicarbonate, after 3 and 6 months of treatment, as compared to baseline (a p-value of ≤ 0.05 will be used to determine statistical significance).
• Safety of piclidenoson in Lowe syndrome including treatment-emergent adverse events (TEAEs) and changes in vital signs, physical examination, neurological examination, clinical laboratory tests (liver, kidney, hematology, chemistry and urinalysis), and ECG.

Inclusion criteria

• Males 18 years and above;
• Documentation of genetically-proven Lowe Syndrome;
• Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73m2, as calculated by the CKD-EPI equation;
• Male subjects must refrain from sperm donation during treatment and until at least 1 month after the last dose of study medication. Male subjects must agree to use condoms throughout the course of the trial and for 1 month after the last dose of study medication;
• Ability to complete the study in compliance with the protocol; and
• Ability to understand and provide written informed consent (subject or legal guardian).

Exclusion criteria

• Subjects receiving chronic therapies not related to Lowe syndrome; Estimated glomerular filtration rate (eGFR) <40 mL/min/1.73m2 by the CKD-EPI equation;
• Liver aminotransferase levels greater than 1.5 times the laboratory's upper limit of normal;
• QTcF interval > 450 milliseconds (msec) on ECG (average of triplicate ECGs) (except when QT prolongation is associated with right or left bundle branch block or cardiac pacemaker, in which case enrollment is allowed);
• A condition which increases proarrhythmic risk, including hypokalemia, hypomagnesemia, or congenital Long QT Syndrome;
• Ongoing or planned use of a concomitant medication that is on the CredibleMedsTM list of drugs known to cause Torsades des Pointes; https://crediblemeds.org/;
• Active gastrointestinal disease which could interfere with the absorption of oral medication;
• Active drug or alcohol dependence;
• Concomitant use of strong cytochrome P450 inducers, e.g., rifampin, phenobarbital, phenytoin, carbamazepine;
• Significant acute or chronic medical or psychiatric illness, including chronic systemic infection or malignancy, that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study; and
• Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to the Screening visit.