Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
4
Countries
1
Sites
1
Dent 2 disease
The primary aim of the study is to test the efficacy of alpelisib to increase renal uptake of 99mTc-labeled DMSA as a measure the reabsorption capacity of LMWPs by renal proximal tubules. Patients will be treated for 4 weeks at a starting oral dose of 50 mg/day for 1 week, followed by 150 mg/day for 3 weeks.
Key facts
- Sponsor
- Ospedale Pediatrico Bambino Gesu
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Male Urogenital Diseases [C12]
- Trial duration
- 14 Mar 2025 → ongoing
- Decision date (initial)
- 2025-01-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- The Lowe Syndrome Trust · Dent Disease Foundation · The Lowe Syndrome Association
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The primary aim of the study is to test the efficacy of alpelisib to increase renal uptake of 99mTc-labeled
DMSA as a measure the reabsorption capacity of LMWPs by renal proximal tubules.
Patients will be treated for 4 weeks at a starting oral dose of 50 mg/day for 1 week, followed by 150
mg/day for 3 weeks.
Secondary objectives 1
- 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. 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.
Conditions and MedDRA coding
Dent 2 disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10069199 | Dent's disease | 100000004850 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | ALPEDENT study A no-profit, open-label, phase II pilot study on the efficacy and safety of
Alpelisib in patients with Dent 2 disease.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- No
- IPD plan description
- none
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Subjects who meet all of the following criteria are eligible for this clinical trial: a. Age ≥18 years b. Genetically proven Dent 2 disease c. eGFR ≥ 50 ml/min/1.73 m2, as calculated by the CKD-EPI equation d. Expected compliance to the study protocol e. Signed Informed Consent Form (ICF)/Assent by the subject f. Since Dent 2 is an X–linked disease, only male patients will be enrolled
Exclusion criteria 1
- Subjects meeting one or more of the following criteria cannot be included in the study: a. Patients suffering from co-morbidities, including malignancies b. Patients with any chronic infectious condition c. Patients receiving therapies not related to the OCRL mutation d. Patients with mental disabilities e. Patients with diabetes mellitus or baseline fasting glucose levels > 105 mg/dl 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. g. Patients with hypersensitivity to the active substance or to any of the excipients of alpelisib or the 99-mTc labelled-DMSA
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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).
Secondary endpoints 1
- 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). − 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)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Piqray 50 mg and 200 mg film-coated tablets
PRD8235738 · Product
- Active substance
- Alpelisib
- Substance synonyms
- (2S)-N1-(4-METHYL-5-(1-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YL)PYRIDIN-4-YL)-1,3-THIAZOL-2-YL)PYRROLIDINE-1,2-DICARBOXAMIDE, BYL719
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 350 mg milligram(s)
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EM03 — -
- Marketing authorisation
- EU/1/20/1455/004
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/21/2420
- Modified vs. Marketing Authorisation
- No
Piqray 150 mg film-coated tablets
PRD8234894 · Product
- Active substance
- Alpelisib
- Substance synonyms
- (2S)-N1-(4-METHYL-5-(1-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YL)PYRIDIN-4-YL)-1,3-THIAZOL-2-YL)PYRROLIDINE-1,2-DICARBOXAMIDE, BYL719
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 150 mg milligram(s)
- Max total dose
- 3150 mg milligram(s)
- Max treatment duration
- 3 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EM03 — -
- Marketing authorisation
- EU/1/20/1455/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/23/2841
- Modified vs. Marketing Authorisation
- No
Auxiliary 1
RENOCIS 1 mg kit for radiopharmaceutical preparation
PRD891519 · Product
- Active substance
- Dimercaptosuccinic Acid
- Pharmaceutical form
- KIT FOR RADIOPHARMACEUTICAL PREPARATION
- Route of administration
- IV INJECTION, IV INFUSION
- Max daily dose
- 160 MBq megabecquerel(s)
- Max total dose
- 320 MBq megabecquerel(s)
- Max treatment duration
- 6 Week(s)
- Authorisation status
- Authorised
- ATC code
- V09CA02 — TECHNETIUM (99MTC) SUCCIMER
- Marketing authorisation
- PL 11876/0008
- MA holder
- CIS BIO INTERNATIONAL
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ospedale Pediatrico Bambino Gesu
- Sponsor organisation
- Ospedale Pediatrico Bambino Gesu
- Address
- Piazza Di Sant'Onofrio 4
- City
- Rome
- Postcode
- 00165
- Country
- Italy
Scientific contact point
- Organisation
- Ospedale Pediatrico Bambino Gesu
- Contact name
- Francesco Emma
Public contact point
- Organisation
- Ospedale Pediatrico Bambino Gesu
- Contact name
- Francesco Emma
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 4 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2025-03-14 | 2025-06-10 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | ALPEDENT - CRF_forpublication | 1.1 |
| Protocol (for publication) | ALPEDENT - CRF_tc | 1.1 |
| Protocol (for publication) | D Protocol_ALPEDENT_updated_forpublication | 1.9 |
| Protocol (for publication) | D_ ALPEDENT Protocol_updated_tc | 1.9 |
| Recruitment arrangements (for publication) | K_Recruitment arrangements_forpublication | 1 |
| Subject information and informed consent form (for publication) | L_ALPEDENT_Carta ID del paziente_notforpublication | 1 |
| Subject information and informed consent form (for publication) | L_ALPEDENT_OPBG_Privacy Notice_art13-14 RGPD_notforpublication | 1 |
| Subject information and informed consent form (for publication) | L_Lettera_medico_curante_ALPEDENT_notforpublication | 1 |
| Subject information and informed consent form (for publication) | L_Modulo_consenso_adulti_ALPEDENT | 2 |
| Subject information and informed consent form (for publication) | L_Modulo_consenso_adulti_ALPEDENT_tc | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | annex 1 piqray-epar-product-information_en | 1 |
| Synopsis of the protocol (for publication) | D Protocol Synopsis_en_updated_forpublication | 2.1 |
| Synopsis of the protocol (for publication) | D Protocol Synopsis_ita_updated_forpublication | 2.1 |
| Synopsis of the protocol (for publication) | D Protocol Synopsis_laylanguage_updated_forpublication | 2.1 |
| Synopsis of the protocol (for publication) | D_Protocol Synopsis_en_tc | 2.1 |
| Synopsis of the protocol (for publication) | D_Protocol Synopsis_ita_tc | 2.1 |
| Synopsis of the protocol (for publication) | D_Protocol Synopsis_laylanguage_tc | 2.1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-11 | Italy | Acceptable 2025-01-15
|
2025-01-17 |