Alpelisib for Dent 2 disease|Dent's disease

Inclusion criteria

• {"criterion_text":"- Subjects who meet all of the following criteria are eligible for this clinical trial:\n- a. Age ≥18 years\n- b. Genetically proven Dent 2 disease\n- c. eGFR ≥ 50 ml/min/1.73 m2, as calculated by the CKD-EPI equation\n- d. Expected compliance to the study protocol\n- e. Signed Informed Consent Form (ICF)/Assent by the subject\n- f. Since Dent 2 is an X–linked disease, only male patients will be enrolled"}

Exclusion criteria

• {"criterion_text":"- Subjects meeting one or more of the following criteria cannot be included in the study:\n- a. Patients suffering from co-morbidities, including malignancies\n- b. Patients with any chronic infectious condition\n- c. Patients receiving therapies not related to the OCRL mutation\n- d. Patients with mental disabilities\n- e. Patients with diabetes mellitus or baseline fasting glucose levels > 105 mg/dl\n- f. Participants who do not consent to abstinence or to use a highly effective method of contraception for the duration of the study and for one week following discontinuation of alpelisib.\n- g.\tPatients with hypersensitivity to the active substance or to any of the excipients of alpelisib or the 99-mTc labelled-DMSA"}

Primary endpoints

• {"endpoint_text":"- Improvement in the renal uptake of 99mTc-DMSA after 4 weeks of treatment (a p-value of ≤ 0.05 will be used to determine statistical significance).","definition_or_measurement_approach":"Renal uptake of 99mTc-DMSA measured after 4 weeks of treatment as a measure of reabsorption capacity of low-molecular-weight proteins (LMWPs) by renal proximal tubules; statistical significance determined with a p-value ≤ 0.05."}

Secondary endpoints

• {"endpoint_text":"- Improvement of low-molecular weight proteinuria as assessed by changes urinary excretion of retinol-binding protein and beta-2 microglobulin after 4 weeks of treatment (a p-value of ≤ 0.05 will be used to determine statistical significance).","definition_or_measurement_approach":"Assessment of urinary excretion of retinol-binding protein and beta-2 microglobulin after 4 weeks; statistical significance with p ≤ 0.05."}
• {"endpoint_text":"- Improvement of the Fanconi syndrome as assessed by including 24-hour urine volume, urinary excretion of sodium, glucose, phosphate, amino acids, and changes in serum bicarbonate after 4 weeks of treatment (a p-value of ≤ 0.05 to determine statis sign)","definition_or_measurement_approach":"Assessment of Fanconi syndrome parameters including 24-hour urine volume, urinary excretion of sodium, glucose, phosphate, amino acids, and serum bicarbonate changes after 4 weeks; statistical threshold indicated as p ≤ 0.05 (text contains typographical note 'to determine statis sign')."}

Other endpoints

• {"endpoint_text":"- The secondary aims 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 alpelisib in patients with dent 2 disease. At all planned clinical visits, allergic reactions and all vital parameters will be monitored. During the 8 weeks of the study (4 weeks of treatment and 4 weeks of post-treatment evaluation) any adverse events will be recorded. After completion of the 8 week evaluation, patients will be followed-up clinically at 6 and 12 months.","definition_or_measurement_approach":"Safety monitoring: record allergic reactions, vital parameters, and any adverse events during 8-week study period; clinical follow-up visits at 6 and 12 months."}
• {"endpoint_text":"- In addition, we will analyze circulating bone precursors at time 0, 4 weeks, and 8 weeks, to assess potential effects of alpelisib on bone metabolism.","definition_or_measurement_approach":"Analysis of circulating bone precursor cells at baseline, 4 weeks and 8 weeks to evaluate effects on bone metabolism."}

Italy

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

17-01-2025

Processing Time Days

52

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

Ospedale Pediatrico Bambino Gesu

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"The Lowe Syndrome Trust","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Dent Disease Foundation","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"The Lowe Syndrome Association","duties_or_roles":"Source of monetary support","organisation_type":""}