An Open Label, Single Arm, Phase I/II Clinical Study of Autologous CD4+ T-Cells Edited Ex-Vivo at the CD40LG Locus by CRISPR/Cas9 and IDLV-based vector in Patients with X-linked Hyper IgM Syndrome Type 1 (HIGM1)

2025-524635-39-00 Phase I and Phase II (Integrated) - First administration to humans Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - First administration to humans
Status Authorised, recruitment pending
Participants planned 4
Countries 1
Sites 1

X-linked immunodeficiency with hyper-IgM type 1 (HIGM1)

To evaluate safety of the treatment with FT018 in patients with HIGM1

Key facts

Sponsor
Fondazione Telethon Ets, San Raffaele Hospital
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years, 65+ years
Gender
Male
Therapeutic area
Phenomena and Processes [G] - Genetic Phenomena [G05], Diseases [C] - Immune System Diseases [C20]
Decision date (initial)
2026-05-20
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate safety of the treatment with FT018 in patients with HIGM1

Conditions and MedDRA coding

X-linked immunodeficiency with hyper-IgM type 1 (HIGM1)

VersionLevelCodeTermSystem organ class
28.0 PT 10066130 Hyper IgM syndrome 100000004850

Regulatory references

Scientific advice from competent authorities
Italian National Institute Of Health
Plan to share IPD
No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Signature of informed consent
  2. Male subject
  3. ≥ 1year of age
  4. Lansky/Karnofsky ≥ 80%
  5. Genetic diagnosis of HIGM1
  6. Absent/reduced expression or functionality of CD40L on CD4+ T-cells upon in vitro stimulation with PMA/ionomycin
  7. Requirement of chronic IgRT
  8. Good adherence to IgRT

Exclusion criteria 9

  1. CD40LG mutation upstream of the vector insertion site in CD40LG intron 1 or any other mutation not amenable to correction with gene editing
  2. Contraindication to vaccination included in the protocol or other medications/procedures foreseen in the protocol
  3. Exposure to any prior cell or gene therapies
  4. Documented HIV RNA, HCV RNA or HBV DNA positivity, presence of total syphilis antibodies and compliance to Tissue Directive (manufacturing issue)
  5. End-organ dysfunction or other severe disease or clinical condition which, in the judgment of the Investigator, would make the subject inappropriate for entry into this study
  6. Has previously undergone allogeneic hematopoietic stem cell transplantation and has evidence of residual cells of donor origin.
  7. Patient enrolled in other clinical trials
  8. Patient unable to donate a sufficient number of lymphocytes for drug product manufacturing
  9. Systemic corticosteroid therapy or other immunosuppressive drugs that may interfere With apheresis or the DP

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Proportion of patients experiencing dose-limiting toxicities (DLTs) after each drug product (DP) dose

Secondary endpoints 4

  1. Occurrence of: - Adverse events (AEs) - Serious adverse events (SAEs)Adverse events of special interest (AESIs) - DP-related AEs - Immune reconstitution inflammatory Syndrome (IRIS) (number, grading and proportion of patients experiencing IRIS) evaluated at 28 days after each dose, 6 months, 1 year and 2 years after treatment
  2. Proportion of patients receiving the boost DP dose
  3. Overall survival at 6 months, 1 year and 2 years after treatment
  4. Incidence rate, duration and proportion of days with moderate-severe infection in the 2 years preceding and in the 2 years after treatment, evaluated in consecutive 6- month time windows (6 months, 1 year, 1.5 years and 2 years)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Autologous Peripheral Blood-Derived CD4 T-Cells Crispr-Edited at the CD40LG Locus

PRD13416480 · Product

Active substance
Autologous Peripheral Blood-Derived CD4 T-Cells Crispr-Edited at the CD40LG Locus
Substance synonyms
Telethon_028
Pharmaceutical form
DISPERSION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Not Authorised
MA holder
FONDAZIONE TELETHON
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/22/2617

Auxiliary 4

Rabipur Polvere e solvente per soluzione iniettabile in siringa preriempita. Vaccino rabico (inattivato).

PRD13307204 · Product

Active substance
Rabies Virus (Inactivated) Strain Flury Lep
Substance synonyms
Rabies virus (Inactivated, strain Flury LEP)
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Authorisation status
Authorised
ATC code
J07BG01 — RABIES, INACTIVATED, WHOLE VIRUS
Marketing authorisation
035947035
MA holder
BAVARIAN NORDIC A/S
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Infanrix hexa, Powder and suspension for suspension for injection. Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed).

PRD344809 · Product

Active substance
Pertussis Filamentous Haemagglutinin Adsorbed on Aluminium Hydroxide, Hydrated
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Authorisation status
Authorised
ATC code
J07CA09 — DIPHTHERIA-HEMOPHILUS INFLUENZAE B-PERTUSSIS-POLIOMYELITIS-TETANUS-HEPATITIS B
Marketing authorisation
EU/1/00/152/001
MA holder
GLAXOSMITHKLINE BIOLOGICALS S.A.
MA country
EU
Paediatric formulation
Yes
Orphan designation
No
Modified vs. Marketing Authorisation
No

TICOVAC 0,5 ml Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l’encefalite da zecca

PRD2617152 · Product

Active substance
Tick-Borne Encephalitis Virus (Inactivated), Neudoerfl Strain
Substance synonyms
TICK-BORNE ENCEPHALITIS VIRUS INACTIVATED (STRAIN NEUDÖRFL)
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Authorisation status
Authorised
ATC code
J07BA01 — ENCEPHALITIS, TICK BORNE, INACTIVATED, WHOLE VIRUS
Marketing authorisation
036515132
MA holder
PFIZER S.R.L.
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

TICOVAC 0,25 ml per uso pediatrico Sospensione iniettabile in una siringa preriempita Vaccino (virus intero, inattivato) contro l'encefalite da zecca

PRD2617126 · Product

Active substance
Tick-Borne Encephalitis Virus (Inactivated), Neudoerfl Strain
Substance synonyms
TICK-BORNE ENCEPHALITIS VIRUS INACTIVATED (STRAIN NEUDÖRFL)
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
INTRAMUSCULAR INJECTION
Authorisation status
Authorised
ATC code
J07BA01 — ENCEPHALITIS, TICK BORNE, INACTIVATED, WHOLE VIRUS
Marketing authorisation
036515094
MA holder
PFIZER S.R.L.
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Telethon Ets

5 Total trials 2 Recruiting
Commercial
Sponsor organisation
Fondazione Telethon Ets
Address
Via Varese 16 B
City
Rome
Postcode
00185
Country
Italy

Scientific contact point

Organisation
Fondazione Telethon Ets
Contact name
Regulatory Affairs

Public contact point

Organisation
Fondazione Telethon Ets
Contact name
Clinical Development and Operations

San Raffaele Hospital

3 Total trials
Commercial
Sponsor organisation
San Raffaele Hospital
Address
Via Olgettina 58
City
Milan
Postcode
20132
Country
Italy

Sponsor responsibilities

Contact point sponsor
Fondazione Telethon Ets
Article 77 implementation
Fondazione Telethon Ets

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 4 1
Rest of world — 0 —

Investigational sites

Italy

1 site · Authorised, recruitment pending
San Raffaele Hospital
Paediatric hematology & Oncology, Via Olgettina 58, 20132, Milan

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_ Protocol 2025-524635-39-00_redacted 2
Protocol (for publication) D1_ Protocol 2025-524635-39-00_v2_23APR2026_tc 2
Protocol (for publication) D4_questionnaire_PedsQL_Family Impact Module_Std_ENG 1
Protocol (for publication) D4_questionnaire_PedsQL_Family Impact Module_Std_IT 1
Protocol (for publication) D4_questionnaire_PedsQL_Generic Core Scale_Std_all_ENG 1
Protocol (for publication) D4_questionnaire_PedsQL_Generic Core Scale_Std_all_IT 1
Protocol (for publication) D4_questionnaire_PedsQL_Infant Scale_Std_all_ENG 1
Protocol (for publication) D4_questionnaire_PedsQL_Infant Scale_Std_all_IT 1
Recruitment arrangements (for publication) K1_ Recruitment arrangements 2
Subject information and informed consent form (for publication) L1_Assent 12-17Y_OSR_redacted 2
Subject information and informed consent form (for publication) L1_Assent 12-17Y_V 2_30MAR2026_TC 2
Subject information and informed consent form (for publication) L1_assent 6-11y_OSR 1
Subject information and informed consent form (for publication) L1_ICF Adult patients_V 2_30MAR2026_TC 2
Subject information and informed consent form (for publication) L1_ICF parent legal guardian_V 2_30MAR2026_TC 2
Subject information and informed consent form (for publication) L1_ICF_adult patients_OSR_Redacted 2
Subject information and informed consent form (for publication) L1_ICF_parents_legal representatives_OSR_Redacted 2
Subject information and informed consent form (for publication) L1_ICF_patient s pregnant partner_OSR_Redacted 1
Subject information and informed consent form (for publication) L1_letter for family doctor 1
Subject information and informed consent form (for publication) L1_letter to paediatrician 1
Subject information and informed consent form (for publication) L1_Patient Alert Card 1
Subject information and informed consent form (for publication) L1_SIS and ICF_adult patients_OSR_Redacted 2
Subject information and informed consent form (for publication) L1_SIS and ICF_parents_legal representatives_OSR_Redacted 2
Subject information and informed consent form (for publication) L1_SIS_ICF_Adult patients_V 2_30MAR2026_TC 2
Subject information and informed consent form (for publication) L1_SIS_ICF_Parent legal guardian_V 2_30MAR2026_TC 2
Synopsis of the protocol (for publication) D1_ Protocol synopsis_ 2025-524635-39-00_EN 3
Synopsis of the protocol (for publication) D1_ Protocol synopsis_2025-524635-39-00_IT 3

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2026-02-05 Italy Acceptable
2026-05-18
 2026-05-20