Base Editing Hematopoietic Stem Cell Gene Therapy for CD40L-HyperIgM Syndrome: Single Patient Study

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · May 6, 2025

Keywords

ClinConnect Summary

Study Description:

This is a single participant gene therapy study to provide a participant with CD40L c.658C\>T; p.Q220X-Hyper IgM syndrome with autologous base-edited hematopoietic stem/progenitor cells (HSPC). The study hypothesis is that base edited HSPCs will be repaired efficiently and safely to restore CD40L expression and improve immune function.

The study cell product is base edited autologous HSPCs which will be administered as a one-time infusion following myeloid conditioning using busulfan administered once daily for 2 days with a daily target AUC of 4500 micromol\*min/L or a...

Gender

MALE

Eligibility criteria

• • INCLUSION CRITERIA
• This study is a single participant research study and to receive the study product, he needs to meet the following criteria:
• • 1. Provision of signed and dated informed consent form
• • 2. Stated willingness to comply with all study procedures and availability for the duration of the study
• • 3. Has CD40L Q220X mutation
• • 4. Defective class switching
• • 5. Liver abnormalities (transaminases\>UL)
• • 6. Portal hypertension
• • 7. Consensus from Hepatology Consult to receive myeloid conditioning
• • 8. Ability to take oral medication and be willing to adhere to the intervention regimen
• • 9. Use of condoms or other methods to ensure effective contraception with partner
• • 10. Ability of subject to understand and the willingness to sign a written informed consent document
• • EXCLUSION CRITERIA
• An individual who meets any of the following criteria will be excluded from participation in this study:
• • 1. Known allergic reactions to components of the BE HSPC study product
• • 2. Febrile illness within two weeks of hospital admission for treatment
• • 3. Unwilling to submit their information as part of the alemtuzumab \[Campath(R)\] Distribution Program application or the Distribution Program committee has determined the participant is not qualified to receive alemtuzumab.
• • NOTE: Alemtuzumab (campath) (IV formulation) is no longer distributed commercially. To receive product, the physician must contact the program for the participant. If the participant is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol. http://www.campath.com/
• • Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies and NIH protocols 94-I-0073 and 05-I-0213. Consideration for coenrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator in consultation with the medical monitor. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator (in consultation with the medical monitor).