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Recruiting NCT03645486

Lentiviral Gene Therapy for CGD

No phase Interventional Chronic Granulomatous Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Infusion of lentiviral TYF-CGD-modified autologous stem cells.
Who it may be relevant to
Registry conditions: Chronic Granulomatous Disease. Basic parameters: No limits · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Lentiviral Gene Therapy for Chronic Granulomatous Disease (CGD)

Overview

This is a Phase I/II clinical trial of gene therapy for treating Chronic Granulomatous Disease using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the TYF-CGD gene transfer clinical protocol.

Detailed description

Chronic granulomatous disease (CGD) is a rare disorder caused by inherited defects in the NADPH oxidase multienzyme complex. It is associated with severe and life-threatening bacterial and fungal infections. Approximately two-thirds of all CGD cases result from mutations within the X-linked gp91phox gene (CYBB), followed by the autosomal recessive forms of CGD, with defects in the gene coding for p47phox (NCF1) accounting for 10-30% of all CGD cases.

The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-CYBB and TYF-NCF1, the ex-vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment, assessment of vector integration sites, and finally the long-term correction of immune dysfunctions.

Interventions

  • Genetic Infusion of lentiviral TYF-CGD-modified autologous stem cells
    Infusion of lentiviral TYF-modified autologous stem cells at 1\~10x10\^6 gene-modified cells per kg body weight

Primary outcome measures

  • Overall survival [Time frame: 15 year follow up]
  • Gene marking in bone marrow cells [Time frame: 15 year follow up]
Secondary outcome measures (2)
  • Change in infection frequency [Time frame: 1 year after treatment by clinical history, complete physical examination, haematological and microbiological tests]
  • Recovery of immune function [Time frame: 1 year follow up]

Eligibility criteria

Inclusion criteria

  • CGD patients >= 0 years of age
  • Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
  • Karnofsky-Index > =70%
  • At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite drug intervention
  • Written informed consent for adult patient, and assent for pediatric subjects seven years or older

Exclusion criteria

  • Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
  • Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

China · 1 center
  • Shenzhen Geno-immune Medical Institute — Shenzhen

Identifiers

NCT: NCT03645486 · GIMI-IRB-18004

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗