Gene Therapy for Wiskott-Aldrich Syndrome

Not currently recruiting at 1 trial location

Overseen By Orchard Clinical Trials

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Fondazione Telethon

Disqualifiers: Cancer, HIV, Hepatitis B, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called OTL-103 for individuals with Wiskott-Aldrich Syndrome, a rare genetic disorder affecting the immune system and blood clotting. The goal is to determine if this treatment can safely and effectively correct the genetic issue causing the disease. Ideal participants are those diagnosed with Wiskott-Aldrich Syndrome who lack a compatible family member for a stem cell transplant. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that OTL-103 gene therapy could help treat Wiskott-Aldrich Syndrome. This treatment uses a special virus to insert a healthy gene into stem cells. Studies have found that this approach can improve the symptoms of the syndrome. Importantly, these studies also indicate that the treatment is generally safe, with most people tolerating it well and serious side effects being rare. Although still under testing, earlier research suggests it could be a safe option for individuals with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Wiskott-Aldrich Syndrome, which often involve bone marrow transplants or enzyme replacement therapies, OTL-103 offers a groundbreaking approach. This gene therapy uses autologous CD34+ hematopoietic stem cells that are modified outside the body with a lentiviral vector to include the human WAS gene. This means the patient's own stem cells are engineered to correct the genetic defect at its source, potentially providing a long-term solution. Researchers are excited because this treatment could significantly reduce the complications and risks associated with traditional therapies, offering a more direct and potentially curative option.

What evidence suggests that this gene therapy might be an effective treatment for Wiskott-Aldrich Syndrome?

Research has shown that OTL-103 gene therapy, which participants in this trial will receive, could be a promising treatment for Wiskott-Aldrich Syndrome (WAS). In earlier studies, patients who received this therapy experienced improvements in their WAS symptoms. This treatment uses a modified virus to insert the correct gene into the patient’s own stem cells, potentially boosting their immune system. Long-term data suggest that the benefits endure. This therapy offers hope for those with WAS, who currently have few treatment options. ^{1 3 5 6 7}

Who Is on the Research Team?

Orchard Clinical Trials

Principal Investigator

Orchard Therapeutics (Europe) Limited

Are You a Good Fit for This Trial?

This trial is for individuals up to 65 years old with Wiskott-Aldrich Syndrome (WAS), confirmed by genetic mutation and severe symptoms or lack of WAS protein expression. Candidates must not have an identical donor for stem cell transplant, nor any end-organ dysfunction, active infections unresponsive to treatment, serious blood disorders, HIV, prior transplants with remaining donor cells, tuberculosis, hepatitis B or C infection, inability to mobilize stem cells for collection, cancer history except local skin cancer without hereditary syndrome or previous gene therapy.

Inclusion Criteria

I have been diagnosed with WAS through genetic testing.

I don't have a matching family donor for a stem cell transplant.

I am 65 years old or younger.

Exclusion Criteria

I have stable Hepatitis B.

Documented human immunodeficiency virus (HIV) infection

I have shingles that didn't improve with treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gene Therapy Treatment

Participants receive OTL-103 gene therapy, involving autologous CD34+ hematopoietic stem cells transduced with a lentiviral vector encoding the WAS gene

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including successful engraftment and hematological reconstitution

6 months

What Are the Treatments Tested in This Trial?

Interventions

• OTL-103

Trial Overview

The study tests a cryopreserved version of OTL-103 Gene Therapy in patients with WAS. OTL-103 uses the patient's own blood-forming stem cells modified by a lentiviral vector to correct the faulty gene responsible for WAS. It's an open-label study where all participants receive this single intervention without comparison groups.

How Is the Trial Designed?

Group I: Gene Therapy Experimental Treatment 1 Intervention

OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene

Who Is Running the Clinical Trial?

Fondazione Telethon

Lead Sponsor

Trials

20

Recruited

1,500+

Orchard Therapeutics

Lead Sponsor

Trials

23

Recruited

106,000+

Ospedale San Raffaele

Collaborator

Trials

86

Recruited

388,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03837483

NCT03837483 | A Clinical Study to Evaluate the Use of a ...

This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103 Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10731922/

Outcomes of hematopoietic stem cell gene therapy for ...

Labrosse et al report on a phase 1/2 trial of stem cell gene therapy for 5 patients with Wiskott-Aldrich syndrome (WAS) using a self-inactivating lentiviral ...

3.

io.nihr.ac.uk

io.nihr.ac.uk/wp-content/uploads/2022/01/7993-OTL-103-for-Wiskott-Aldrich-Syndrome-V1.0-AUG2020-NON-CONF-2020.pdf

OTL-103 for Wiskott-Aldrich syndrome

Stem cell transplantation is the only treatment currently available to stabilize WAS. OTL-103 is administered intravenously. It is made up of immature bone ...

4.

nature.com

nature.com/articles/s41591-021-01641-x

Long-term safety and efficacy of lentiviral hematopoietic ...

The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

5.

scge.mcw.edu

scge.mcw.edu/platform/data/clinicalTrials/report/NCT03837483

Gene Therapy Trial Report

OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37478401/

Outcomes of hematopoietic stem cell gene therapy for Wiskott ...

These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile.

7.

ashpublications.org

ashpublications.org/blood/article/142/15/1281/497008/Outcomes-of-hematopoietic-stem-cell-gene-therapy

Outcomes of hematopoietic stem cell gene therapy for Wiskott ...

We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral ...