Lowe Syndrome
Conditions
Keywords
Lowe Syndrome, Piclidenoson, CF101, Can-Fite
Brief summary
The primary objective of this trial is to: 1\. Evaluate the efficacy of piclidenoson to increase renal uptake of 99mTc-labeled DMSA, in comparison to baseline, after 6 months (26 weeks) of treatment as a measure the reabsorption capacity of LMWPs by renal proximal tubules. The secondary objectives of this trial are to: 1. Evaluate changes in urinary excretion of LMWPs and other clinical parameters of renal Fanconi syndrome 2. Evaluate safety of piclidenoson in patients with Lowe syndrome
Detailed description
Objectives 1. 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. 2. 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.
Interventions
DRUGPiclidenoson
Piclidenoson will be administered orally at a dose of 3 mg twice per day for 6 months
Sponsors
Can-Fite BioPharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 99mTc-DMSA | 6 months | The primary end-point is to assess whether treatment for 6 months with piclidenoson improves the functioning of renal proximal tubular cells (PTCs), as assessed by the increase in 99mTc-DMSA uptake as compared to Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| beta-2 microglobulin | 3 and 6 months of treatment | Change in low-molecular weight 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 |
| urinary excretion of sodium | 3 and 6 months | Change in the Fanconi syndrome as assessed by 24-hour urine volume, as compared to baseline; urinary excretion of sodium, glucose, phosphate, and amino acids; and changes in serum bicarbonate, after 3 and 6 months of treatment |
| urinary excretion glucose | 3 and 6 months | Change in 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 |
| urinary excretion of phosphate | 3 and 6 months | Change in 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 |
| urinary excretion of amino acids | 3 and 6 months | Change in 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 |
| serum bicarbonate | 3 and 6 months | Change in 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 |
Countries
Italy
Contacts
CONTACTZivit Harpaz
PRINCIPAL_INVESTIGATORFrancesco, MD
Emma
Outcome results
None listed