Autologous haematopoietic stem and progenitor cell population containing CD34+ cells transduced with a lentiviral vector encoding the TCIRG1 cDNA ex vivo expanded for Autosomal recessive osteopetrosis (TCIRG1 mutation)

Inclusion criteria

• {"criterion_text":"- 1. Diagnosis of autosomal recessive osteopetrosis caused by mutations in the TCIRG1 gene, defined by one of the following: Clinical Trial Protocol Document FORM SOP-SC-008.02 Revision 2 Page 16 of 39 EU CT number: 2024-518972-30-00 Protocol number: ARO-FT024-01 Protocol date: 12/02/2025 Protocol version: 1.0 TEMP SOP-GEN-000.05 Rev.4 a. Clinical features of osteopetrosis and documented pathogenic/likely pathogenic biallelic variants (homozygosity or compound heterozygosity, whereby at least 1 allele must contain a known pathogenic mutation) in the TCIRG1 gene causing malignant infantile osteopetrosis. b. If a patient presents with clinical features suggestive of severe osteopetrosis (e.g., generalized osteosclerosis, club-shaped long bones, skull base sclerosis, recurrent fractures and osteomyelitis, cranial nerve entrapment leading to visual and/or hearing loss, bone marrow insufficiency) and at least one pathogenic/likely pathogenic mutation of the TCIRG1 gene.\n- 2. Age: ≥ 28 days and ≤ 2 years old\n- 3. Body weight: ≥ 4 kg"}

Exclusion criteria

• {"criterion_text":"- 1. Availability of a medically appropriate, logistically feasible, fully HLA-matched (10/10) sibling or unrelated donor. The chances of finding a suitable, fully matched unrelated donor should be estimated through a preliminary donor bank search by an experienced transplant team. If the patient is judged unlikely to be treated with a fully matched allogeneic HSCT within 6 weeks from activating search procedures, he/she can be considered eligible for this gene therapy study. This criterion will not be applied to patients whose country of origin does not offer an allogeneic HSCT as a treatment option."}

Primary endpoints

• {"endpoint_text":"- a. Overall survival following the first ATMP infusion.\n- b. Percentage of patients who experience absence of neutropenia or thrombocytopenia > grade 3 and no regular need of red blood cell (RBC) transfusions as compared to baseline in the patients with long-term engraftment of TCIRG1 LVV-transduced cells, as defined by vector copy number (VCN) > 0.2 in total blood or myeloid cells at 12 months post first ATMP infusion, in the absence of rescue treatments (allogeneic transplantation +/- autologous back-up infusion).","definition_or_measurement_approach":"- a. Measured as overall survival status following the first ATMP infusion (time period not further specified in primary endpoint text).\n- b. Defined/measured by absence of neutropenia or thrombocytopenia > grade 3 and no regular need of RBC transfusions compared to baseline in patients with long-term engraftment, where long-term engraftment is defined by vector copy number (VCN) > 0.2 in total blood or myeloid cells at 12 months post first ATMP infusion, assessed in the absence of rescue treatments."}

Secondary endpoints

• {"endpoint_text":"- Secondary Endpoints of Safety a. Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) attributed to procedures related to the harvesting of HSPCs, to conditioning or to ATMP (0-24 months from the first ATMP administration). b. Absence of malignancy or abnormal clonal proliferation evaluated at 6, 12 and 24 months post first ATMP infusion. c. Absence of Replication Competent Lentivirus at 1, 6, 12 and 24 months post first ATMP infusion.\n- Secondary Endpoints of Feasibility a. Percentage of patients for whom at least the minimum number of autologous HSPCs (≥10x106 CD34+ cells/kg, as specified in the protocol) can be collected for manufacturing. b. Percentage of patients for whom a FT024 product conforming to specifications was manufactured and released.\n- Secondary Endpoints of Efficacy: a. Disability-free survival at baseline and at 24 months post first ATMP infusion, defined as absence of ≥ grade 3 neutropenia/thrombocytopenia, no requirement for chronic transfusion of blood products, no osteomyelitis, no requirement for major neurosurgery, and no pathologic bone fractures during the previous 12 months. b. Time to achieve hematologic recovery§ from the first ATMP infusion.\n- Secondary Endpoints of Efficacy: c. Percentage of patients who do not require a rescue treatment (autologous back-up infusion and/or allogeneic transplant). d. Change in neutrophil counts and platelets levels at 1, 2, 3, 6, 9, 12, 18 and 24 months post first ATMP infusion from baseline. e. Change in monthly RBC and platelets transfusion requirement at 1, 2, 3, 6, 12, 18 and 24 months post first ATMP infusion from baseline.\n- Secondary Endpoints of Efficacy: f. Impact of boost infusion on hematological recovery (neutrophils and platelets levels, RBC and platelets transfusions). g. Engraftment of TCIRG1 LVV-transduced cells, as assessed by longitudinal analysis of vector copy number (VCN) in leukocyte populations from blood and/or bone marrow at 1, 2, 3, 6, 9, 12, 18 and 24 months post first ATMP infusion.\n- Secondary Endpoints of Efficacy: h. Percentage of patients who experience long-term engraftment of TCIRG1 LVV-transduced cells, as defined by vector copy number (VCN) >0.2 in total blood or myeloid cells at 12 months post first ATMP infusion, in the absence of neutropenia or thrombocytopenia > grade 3 and no regular need of RBC transfusions as compared to baseline, in the absence of rescue treatments (allogeneic transplantation +/- autologous back-up infusion), stratified by number of boost.\n- Secondary Endpoints of Efficacy: i. Quality of life (PedsQL 4.0 generic core - Parent-proxy report for Toddler (2-4 years), PedsQL Infant Scales, Stem-cell transplant module), parents reported outcome measures at baseline and at 12 and 24 months after the first ATMP infusion.","definition_or_measurement_approach":"- Safety endpoints measured as frequency/severity of AEs/SAEs related to HSPC harvesting, conditioning or ATMP over 0-24 months; malignancy/clonal proliferation assessed at 6, 12, 24 months; RCL testing at 1,6,12,24 months.\n- Feasibility endpoints measured as % of patients with ≥10x10^6 CD34+ cells/kg collected and % with FT024 product manufactured and released according to specifications.\n- Efficacy endpoints include disability-free survival at 24 months (as defined in text), time to hematologic recovery, % avoiding rescue treatment, longitudinal changes in neutrophil/platelet counts and transfusion requirements at specified timepoints, impact of boost infusion on hematological recovery, engraftment assessed by longitudinal VCN in blood/bone marrow at specified timepoints, long-term engraftment defined by VCN >0.2 at 12 months, and QoL measured by listed PedsQL instruments at baseline, 12 and 24 months."}

Italy

Earliest CTIS Part Ii Submission Date

03-06-2025

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

275

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Fondazione Telethon Ets

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Contract research organisations

Name

Iqvia Rds Italy S.r.l.

Responsibilities

1,10,6,7,8

Name

Marken Italy S.r.l.

Responsibilities

14

Name

Phse S.r.l.

Responsibilities

14

Third parties

• {"country":"Italy","full_name":"Fondazione IRCCS Policlinico San Matteo","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Iqvia Rds Italy S.r.l.","duties_or_roles":"1,10,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Marken Italy S.r.l.","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico","duties_or_roles":"13","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Phse S.r.l.","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Genosafe S.A.S.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Fondazione IRCCS San Gerardo Dei Tintori","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}

Co-sponsors

• San Raffaele Hospital