Gene Therapy for Bubble Boy Disease

Recruiting at 1 trial location

Overseen By Suk S De Ravin, M.D.

Age: < 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Disqualifiers: Hematologic malignancy, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for individuals with X-linked severe combined immunodeficiency (XSCID), also known as "Bubble Boy Disease." The goal is to determine if Lentiviral Gene Transfer can safely enhance the immune system in patients who continue to experience significant immune issues after a previous stem cell transplant. Participants should have XSCID, a serious immune disorder, with ongoing problems such as frequent infections, poor growth, or other immune-related issues despite a prior transplant. The study aims to improve immune function using a safer version of gene therapy, designed to avoid past risks like leukemia. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves gene therapy and conditioning with busulfan, it's important to discuss your current medications with the trial team to ensure there are no interactions.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that lentiviral gene therapy for treating X-linked severe combined immunodeficiency (XSCID), also known as "bubble boy disease," has been safe in previous studies. These studies used lentiviral vectors with low doses of busulfan, a chemotherapy drug that prepares the body for therapy. The results generally showed only mild and manageable side effects.

This therapy is gaining attention because it is safer than older methods. Previous gene therapy for XSCID had serious side effects like leukemia, but the new lentiviral method aims to reduce these risks.

In summary, past patients generally handled the lentiviral gene therapy well, with only mild side effects reported, making it a potentially safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for XSCID?

Researchers are excited about the lentiviral gene transfer treatment for Bubble Boy Disease, or Severe Combined Immunodeficiency (SCID), because it offers a groundbreaking approach compared to the standard bone marrow transplants or enzyme replacement therapies. This gene therapy uses a lentivirus to deliver a corrected version of the faulty gene directly into the patient's own stem cells, potentially providing a long-term solution by addressing the root cause of the disease. Unlike traditional treatments that may require lifelong management and have limited effectiveness, this approach aims to restore the immune system's function more effectively and could eliminate the need for ongoing treatments. By targeting the genetic basis of the disease, this innovative therapy promises a more comprehensive and lasting impact.

What evidence suggests that this gene therapy could be an effective treatment for XSCID?

Research has shown that using a lentiviral vector for gene therapy holds promise for treating severe combined immunodeficiency, a condition that greatly weakens the immune system. Studies have found this method to be safer and more effective for patients with this condition. Previous trials in Europe successfully treated infants using this approach, demonstrating its efficacy. In this trial, participants will receive a safer version of the lentiviral vector, developed to prevent issues like leukemia, which occurred previously. Early results from other studies indicate that combining this gene therapy with low-dose busulfan, a drug that prepares the bone marrow, can lead to successful treatment outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

Suk S De Ravin, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for children and adults aged 2 to 40 with X-linked severe combined immunodeficiency (XSCID) who lack a matched sibling bone marrow donor, may have had an unsuccessful half-matched transplant, and show significant immune impairment. Participants must weigh at least 10 kg, be HIV negative, have documented B cell dysfunction or need for IVIG therapy, and be able to comply with the study's long-term follow-up.

Inclusion Criteria

Your doctor needs to believe that you have a supportive family and social situation that will help you follow the study's plan and long-term check-ups.

My DNA test shows a mutation in the common gamma chain gene.

I am between 2 and 40 years old and weigh at least 10 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive a total busulfan dose to condition their bone marrow, followed by an infusion of autologous transduced CD34+HSC

1 week

Daily visits for busulfan administration and monitoring

Gene Transfer Treatment

Patients receive a single infusion of the transduced cells and are monitored for safety and efficacy

1 week

Inpatient stay for infusion and initial monitoring

Follow-up

Participants are monitored for engraftment, expansion, and function of gene-corrected lymphocytes, as well as safety and clinical benefit

2 years

Frequent visits for laboratory and clinical evaluations

Long-term Follow-up

Long-term safety and efficacy evaluation as recommended by FDA Guidance for gene transfer treatment studies

At least 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Lentiviral Gene Transfer

Trial Overview The trial tests gene transfer using lentiviral vectors in patients' own blood stem cells to treat XSCID. The process involves collecting these cells from the patient, treating them with a corrective gene vector in culture, then returning them via vein after pre-treatment with low-dose busulfan chemotherapy and palifermin to reduce mucositis side effects.

How Is the Trial Designed?

Group I: cohort b Experimental Treatment 3 Interventions

Patients 9 and Beyond

Group II: cohort a Experimental Treatment 3 Interventions

First 8 Patients Treated

Lentiviral Gene Transfer is already approved in United States for the following indications:

Approved in United States as Lentiviral Gene Transfer for:

• X-linked severe combined immunodeficiency (XSCID)

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Therapeutic gene transfer is increasingly showing promise as a lasting treatment for previously untreatable diseases, with successful outcomes reported in various genetic disorders and cancers, including restoration of vision and eradication of blood cancers.

Approximately 2,000 clinical trials have been conducted or are ongoing, demonstrating significant advancements in gene therapy vector design and successful treatments, particularly in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of gene therapy: results and lessons from recent successes. Kumar, SR., Markusic, DM., Biswas, M., et al.[2022]

Gene therapy has been under investigation for over 5 years, showing promise in safety, toxicity, and efficacy, particularly for treating malignant brain tumors through retroviral-mediated gene insertion.

Current trials are exploring 'suicide' gene therapy for children with recurrent brain tumors and adults with gliomas, indicating a significant potential for gene therapy to transform the management of neurological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for neurologic disease: benchtop discoveries to bedside applications. 2. The bedside. Maria, BL., Medina, CD., Hoang, KB., et al.[2017]

Lentiviral vectors are promising for gene therapy because they can effectively infect both dividing and non-dividing cells, which is crucial for sustained therapeutic gene expression without adverse effects.

Foamy viruses are emerging as another potential vector for gene therapy, also capable of targeting non-dividing cells, indicating a growing interest in diverse viral vectors for effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lentivirus and foamy virus vectors: novel gene therapy tools. Pandya, S., Klimatcheva, E., Planelles, V.[2019]

Lentiviral gene therapy has shown promise as an effective treatment for primary immunodeficiencies (PIDs), with significant advancements in clinical trials for conditions like Wiskott-Aldrich syndrome and ADA-SCID, indicating potential long-term benefits for patients.

Current gene therapy approaches primarily use ex-vivo methods with patients' own stem cells, but emerging techniques like in-vivo gene therapy may enhance treatment options for certain rare genetic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in gene therapy for primary immunodeficiencies using lentiviral vectors. Sauer, AV., Di Lorenzo, B., Carriglio, N., et al.[2022]

Gene therapy has the potential to treat both inherited and acquired diseases, particularly primary immunodeficiency diseases, by correcting genetic defects in a patient's own cells.

The first gene therapy protocol for ADA deficiency severe combined immunodeficiency (SCID) shows promise, indicating that gene therapy could be a viable option for treating various genetic disorders, especially those that can be addressed through bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for primary immunodeficiency disease. Blaese, RM., Culver, KW.[2012]

Lentiviral vectors are a promising tool in gene therapy because they can effectively deliver genes to both dividing and non-dividing cells, making them suitable for a wider range of diseases compared to traditional retroviral vectors.

This chapter provides a comprehensive overview of lentiviral vector design, their applications in treating various diseases, and important safety considerations, highlighting their potential for permanent genetic modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lentiviral vectors and gene therapy. Klimatcheva, E., Rosenblatt, JD., Planelles, V.[2019]

Gene therapy has shown promising results in treating severe combined immunodeficiency (SCID) by correcting T-cell immunodeficiency, with sustained effects observed in clinical trials over the past decade.

Advancements in vector technology, such as the use of lentiviral vectors and the removal of oncogenic elements from retroviral vectors, aim to enhance the safety and efficacy of gene therapy, reducing the risk of leukemia associated with earlier treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for primary adaptive immune deficiencies. Fischer, A., Hacein-Bey-Abina, S., Cavazzana-Calvo, M.[2013]

Lentiviruses are promising tools for gene therapy because they can effectively integrate therapeutic genes into both dividing and non-dividing cells, which is crucial for long-term treatment benefits.

Successful gene therapy requires vectors that are safe, nonpathogenic, and elicit minimal immune responses, making lentiviruses ideal candidates due to their ability to stably deliver genes without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vectors derived from the human immunodeficiency virus, HIV-1. Barker, E., Planelles, V.[2019]

Retroviral vectors, including gretroviral and lentiviral types, have been used in over 350 gene therapy studies, demonstrating their effectiveness in providing long-term and stable expression of therapeutic genes, particularly for treating monogenic inherited diseases like immunodeficiencies.

The analysis of insertional mutagenesis incidents has led to the development of safer lentiviral vectors, enhancing the safety profile of gene therapy and paving the way for treating a broader range of diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retroviral vectors for gene therapy. Maier, P., von Kalle, C., Laufs, S.[2012]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/search/research-news/1634/

Gene Therapy Advances To Better Treat... (NPR News) - NCBI Lentiviral vector gene therapy combined with low-exposure, targeted busulfan conditioning in infants with newly diagnosed SCID-X1 had low-grade acute toxic ...

2. nature.com nature.com/articles/d41587-019-00015-6

'Bubble boy' gene therapy reignites commercial interest Industry interest reignited by increased safety and efficacy of lentiviral gene therapies in several severe combined immune deficiencies.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1815408

Lentiviral Gene Therapy Combined with Low-Dose ... This study showed the successful use of a lentiviral vector combined with low-exposure, targeted busulfan conditioning as the primary treatment ...

4. sciencemediacentre.es sciencemediacentre.es/en/gene-therapy-effective-long-term-children-serious-rare-disease

Gene therapy is effective in children with a serious rare ... My conclusion is that this is a highly relevant study in a disease as rare as severe combined immunodeficiencies (the so-called "bubble boy" ...

5. ir.mustangbio.com ir.mustangbio.com/news-events/press-releases/detail/143/mustang-bio-announces-updated-interim-data-on-x-linked

Mustang Bio Announces Updated Interim Data on X-Linked ... Mustang Bio Announces Updated Interim Data on X-Linked Severe Combined Immunodeficiency Treatment with Lentiviral Vector Gene Therapy Support ...

6. ir.mustangbio.com ir.mustangbio.com/news-events/press-releases/detail/140/mustang-bio-announces-data-on-treatment-with-lentiviral

Press Releases Data represent largest cohort of infants with XSCID, also known as bubble boy disease, who received lentiviral gene therapy with the longest follow-up to date.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03601286

NCT03601286 | Lentiviral Gene Therapy for X-linked ... This trial will determine whether gene therapy for SCID-X1 using a lentiviral vector is safe, feasible and effective. Official Title. Phase I/II Study of ...