Open-label Gene Therapy Study in p47-CGD

Inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

• Properly completed and signed informed consent or assent (participant/legally authorised representative).
• Confirmed diagnosis of CGD due to p47phox deficiency (confirmed mutation in the NCF1 gene by molecular genetic testing).
• Absent or > 95% reduced biochemical activity of NADPH oxidase in a dihydrorhodamine (DHR) flow cytometric test.
• Male or female aged ≥ 18 months and have a body weight ≥ 10 kg at the time of signing the informed consent or assent.
• One or more ongoing or recurrent severe infectious and/or inflammatory complications, at the discretion of the Investigator.

Note: Participants must not have an uncontrolled active infection at the time of screening or apheresis. Infectious or inflammatory complications should be clinically stable (e.g., afebrile, hemodynamically stable, and on appropriate antimicrobial/anti-inflammatory therapy if indicated) before initiation of screening procedures and prior to leukapheresis.

• Lack of an available 10/10 HLA-matched (A, B, C, DR, DQ) sibling donor suitable for HSCT.
• Ability to return to the study site for follow-up during the 1-year on-study, and to the local HSCT site during the off-protocol monitoring period.
• Female participants of childbearing potential must have a negative serum pregnancy test result performed within 3 days prior to starting each cycle of mobilisation and within 5 days prior to infusion of busulfan and must not be pregnant, lactating, or planning a pregnancy from Screening to Month 12 after SGX-001 administration.

Note: Female participants of childbearing potential will be included if they are either sexually inactive (abstinent) for 90 days prior to starting the first cycle of mobilisation, or are using a highly effective birth control methods (i.e., results in < 1% failure rate when used consistently and correctly).

Note: Sexual abstinence or use of contraceptive measures must continue throughout the study and for 12 months after the administration of SGX-001.

• Male participants with female partners of childbearing potential must use highly effective methods of birth control during their participation in the study and for 12 months after the administration of SGX-001.
• Willingness and ability of the participant (or a legally authorised representative, as applicable) to comply with long-term follow-up requirements for a total duration of up to 15 years after administration of SGX-001 through participation in a dedicated LTFU study.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Participant or parent/legal guardian is unable or unwilling to comply with the protocol requirements.
• Availability of a willing 10/10 HLA-matched (A, B, C, DR, DQ) sibling donor unless there is an unacceptable risk associated with an allogeneic HSCT procedure.
• Previous allogeneic HSCT.
• Pregnancy or lactation.
• Contraindications to any of the following:

• CD34+ cell mobilisation procedure (haemoglobin < 8 g/dL, cardiovascular instability, severe coagulopathy).
• Apheresis procedure.
• Conditioning regimen.
• Contraindication for administration of filgrastim, lenograstim, plerixafor, busulfan, or any component of the study intervention.
• Concomitant human immunodeficiency virus (HIV1 or HIV2), hepatitis B virus (HBV), hepatitis C virus (HCV), adenovirus, parvovirus B19, human T-lymphotropic virus (HTLV1 2), or toxoplasmosis infection.
• Evidence of active metastatic or locoregionally advanced malignancy (including haematologic malignancy) for which survival is anticipated to be less than 3 years.
• Significant organ dysfunction/co-morbidity, including but not limited to: mechanical ventilation, shortening fraction on echocardiogram < 25%, renal failure (defined as dialysis dependence), uncontrolled seizure disorder, major congenital anomaly, expected survival < 6 months.
• Inability to stop using IFN gamma at least 30 days prior to administration of the study intervention.
• Participation in another interventional clinical study within 6 months prior to enrolment.
• Presence of any condition that, in the opinion of the Investigator, may compromise the safety or compliance of the participant or would preclude the participant from successful completion of the study or would interfere with interpretation of the study results.