SBT101 Gene Therapy for Adrenomyeloneuropathy

(PROPEL Trial)

No longer recruiting at 1 trial location

Overseen By Clinical Trial Recruitment

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: SwanBio Therapeutics, Inc.

Must not be taking: Steroids, Sirolimus, Tacrolimus, Anesthetics

Disqualifiers: Inflammatory cerebral disease, Diabetes, others

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

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 SBT101 for individuals with adrenomyeloneuropathy (AMN), a condition affecting the spinal cord that can impair walking and balance. The trial aims to determine if SBT101, administered directly into the spinal cord, is safe and effective. Participants will either receive the actual treatment or undergo a procedure that mimics it without delivering the therapy. Individuals with AMN confirmed by genetic testing who can still walk independently might be suitable candidates for this study. As a Phase 1/Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have contraindications (reasons not to use) for steroids, sirolimus, tacrolimus, or anesthetic medications, you may not be eligible to participate.

Is there any evidence suggesting that SBT101 is likely to be safe for humans?

Research has shown that SBT101, a gene therapy for adrenomyeloneuropathy (AMN), is generally safe for patients. Early results from the PROPEL trial indicated that SBT101 is safe for adults with spinal cord disease, with no severe side effects linked to the treatment. In animal studies, SBT101 caused no deaths or noticeable health problems. While these findings are promising, the treatment is still under study to confirm its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for adrenomyeloneuropathy?

SBT101 is unique because it is a gene therapy specifically targeting adrenomyeloneuropathy (AMN). Unlike current treatments, which primarily focus on managing symptoms with medications like corticosteroids or physical therapy, SBT101 aims to address the underlying genetic cause of AMN by delivering therapeutic genes directly into the spinal cord. This approach has the potential to not only slow the progression of the disease but also improve neurological function, offering hope for a more effective and long-lasting solution. Researchers are excited because this innovative method could revolutionize the way AMN is treated, moving from symptomatic relief to potentially altering the disease's course.

What evidence suggests that SBT101 might be an effective treatment for adrenomyeloneuropathy?

Research has shown that SBT101, which participants in this trial may receive, is a promising gene therapy for adrenomyeloneuropathy (AMN). In early lab studies, SBT101 successfully delivered a healthy version of the ABCD1 gene to the spinal cord, aiding in the production of an important protein needed to treat AMN. The treatment was well-tolerated, with no serious side effects reported. These early results suggest that SBT101 could help people with AMN by addressing the genetic cause of the disease. Although more research in humans is needed, the initial findings are encouraging. Participants in this trial may also receive an imitation procedure, which mimics treatment with SBT101 but does not infuse anything into the spinal cord. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18-65 with adrenomyeloneuropathy (AMN), able to walk, diagnosed with X-linked adrenoleukodystrophy (ALD) confirmed by genetic testing and high VLCFA levels. Not eligible if they have unstable adrenal function, prior gene therapy, MRI or anesthesia contraindications, diabetes/high blood sugar, inflammatory brain disease history, or over 15 years since myeloneuropathy onset.

Inclusion Criteria

I have been diagnosed with X-linked adrenoleukodystrophy (ALD) confirmed by genetic testing.

My spinal cord is affected, but I can still walk on my own.

Exclusion Criteria

I have had inflammation in my brain.

I have undergone gene therapy.

I have diabetes or my blood sugar/A1C levels are high.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Two doses of SBT101 will be evaluated to establish the maximum tolerated dose

24 months

Regular visits as per study protocol

Dose-Expansion

Additional patients will be enrolled to receive SBT101 at the maximum tolerated dose

24 months

Regular visits as per study protocol

Long-term Safety Follow-up

An unblinded 3-year follow-up period to evaluate the safety of SBT101 and disease progression

3 years

Annual follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Imitation Procedure
• SBT101

Trial Overview The trial is testing SBT101 gene therapy for AMN via a one-time spinal injection compared to an imitation procedure. It's a blind study where patients are monitored for safety and effectiveness over two years; those on SBT101 continue follow-up for three more years.

How Is the Trial Designed?

Group I: Active Treatment Experimental Treatment 1 Intervention

Patients treated with SBT101

Group II: Imitation Procedure Placebo Group 1 Intervention

Procedure that mimics treatment with SBT101, but does not infuse anything into the spinal cord

Who Is Running the Clinical Trial?

SwanBio Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

80+

Published Research Related to This Trial

The case study highlights adrenomyeloneuropathy, characterized by slowly progressive spastic paraparesis, mild peripheral neuropathy, and adrenal insufficiency.

Dietary therapy has the potential to prevent further progression of neurological symptoms in patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adrenomyeloneuropathy]. Bak, S.[2006]

In a study of 27 Dutch patients with adrenomyeloneuropathy (AMN), 63% developed cerebral demyelination approximately 10.2 years after the onset of symptoms, indicating a higher frequency than previously reported.

The mean survival for these patients was only 3.4 years, suggesting that cerebral demyelination in AMN is associated with a poor prognosis similar to that seen in childhood cerebral adrenoleukodystrophy, highlighting the urgent need for effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent occurrence of cerebral demyelination in adrenomyeloneuropathy. de Beer, M., Engelen, M., van Geel, BM.[2014]

Using an osmotic pump to deliver adeno-associated viral (AAV) vector into the cerebrospinal fluid of mice allows for efficient gene transfer across the spinal cord, which is crucial for treating adrenoleukodystrophy (ALD).

This method resulted in a 20% reduction in very long-chain fatty acids (VLCFAs) in the spinal cord, while minimizing systemic leakage into organs like the liver and heart, suggesting a safer and more effective approach for gene therapy in neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal Adeno-Associated Viral Vector-Mediated Gene Delivery for Adrenomyeloneuropathy. Gong, Y., Berenson, A., Laheji, F., et al.[2020]

AAV9 gene therapy targeting Schwann cells effectively delivered the GJB1 gene, leading to improved motor performance and nerve function in Gjb1-null mice, which model X-linked Charcot-Marie-Tooth disease (CMT1X).

The treatment resulted in enhanced myelination, reduced inflammation in peripheral nerves, and significant improvements in blood biomarkers, suggesting a promising therapeutic approach for CMT1X.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy. Kagiava, A., Karaiskos, C., Richter, J., et al.[2023]

A single lumbar intrathecal injection of a lentiviral vector successfully delivered the GJB1 gene to Schwann cells in a mouse model of X-linked Charcot-Marie-Tooth Disease, resulting in stable expression in up to 50% of these cells.

This gene therapy approach significantly improved motor performance and nerve function in treated mice, demonstrating potential for a new treatment strategy for inherited demyelinating peripheral neuropathies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy. Kagiava, A., Sargiannidou, I., Theophilidis, G., et al.[2022]

A herpes simplex virus (HSV)-based vector was developed to regulate erythropoietin (EPO) expression, which can be tightly controlled by doxycycline, showing potential for treating chronic neuropathy.

In a mouse model of diabetes, continuous administration of doxycycline led to significant protection against neuropathy over 3 months, indicating the vector's efficacy and suitability for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element. Wu, Z., Mata, M., Fink, DJ.[2021]

Hematopoietic stem cell transplant (HSCT) outcomes for X-linked adrenoleukodystrophy (ALD) have improved significantly due to early detection and better treatment protocols, leading to better management of the disease.

Gene therapy has shown promise in halting disease progression in boys with childhood cerebral ALD, and the implementation of Newborn Screening (NBS) allows for early MRI monitoring, changing the prognosis for this serious neurological condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Landscape of Hematopoietic Stem Cell Transplant and Gene Therapy for X-Linked Adrenoleukodystrophy. Mallack, EJ., Turk, B., Yan, H., et al.[2021]

Gene therapy using rAAV1.NT-3 delivered to muscle can effectively increase neurotrophin-3 (NT-3) levels in the blood, leading to significant improvements in motor function and nerve health in a mouse model of Charcot-Marie-Tooth disease (CMT1A).

This approach not only establishes a therapeutic dose and a muscle-specific promoter for sustained NT-3 delivery but also sets the stage for future clinical trials in CMT1A and potentially other nerve regeneration disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV1.NT-3 gene therapy for charcot-marie-tooth neuropathy. Sahenk, Z., Galloway, G., Clark, KR., et al.[2022]

In a study involving three generations of a family, three adults were diagnosed with adrenomyeloneuropathy and two children with adrenoleukodystrophy, highlighting the importance of recognizing these conditions as different presentations of the same genetic disorder.

The identification of a novel mutation (P543L) in the adrenoleukodystrophy gene, along with elevated levels of very long chain fatty acids, underscores the need for early diagnosis to facilitate genetic counseling and improve future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adrenomyeloneuropathy in patients with 'Addison's disease': genetic case analysis. Mukherjee, S., Newby, E., Harvey, JN.[2022]

An optimized adenoviral vector injection into the sciatic nerve of young rats resulted in peak expression of the lacZ gene between 10 and 14 days with minimal tissue injury, suggesting a safer method for gene therapy in peripheral neuropathy.

In adult mice, the immune response significantly limits the expression of the lacZ gene from adenoviral vectors, but this limitation can be overcome with immunosuppression, indicating potential for using these vectors in gene therapy for conditions like CMT1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of cell-mediated immunity prolongs adenovirus-mediated transgene expression in sciatic nerve. Jani, A., Menichella, D., Jiang, H., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05394064

A Study to Evaluate Administration of SBT101 Gene ... This is a Phase 1/2 randomized, blinded, dose-escalation study to evaluate the safety and efficacy of intrathecal (IT) administration of SBT101, a recombinant ...

2. cell.com cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(24)00170-0

An in vitro and in vivo efficacy evaluation of gene therapy ... SBT101 was well tolerated, with no observed SBT101-related mortality or clinical signs. These findings not only provide preclinical efficacy ...

3. synconaltd.com synconaltd.com/news-insights/news/spur-therapeutics-publishes-preclinical-proof-of-concept-data-for-sbt101-its-gene-therapy-candidate-in-adrenomyeloneuropathy-amn/

Spur Therapeutics Publishes Preclinical Proof-of-Concept ... Data show SBT101 effectively delivered a functional copy of the ABCD1 gene to spinal cord tissues with resultant protein expression, ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-sbt101-gene-therapy-for-adults-with-adrenomyeloneuropathy/

Study on the Safety and Effectiveness of SBT101 Gene ... This study investigates the safety and effectiveness of SBT101 gene therapy in treating adults diagnosed with the genetic disorder Adrenomyeloneuropathy.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12383759/

Gene Therapy of Adrenomyeloneuropathy - PubMed Central The results of this trial, based on a single IT bolus of the SBT101 vector and expected in 2028, will be important to analyze [172]. 8.3. Gene ...

6. cgtlive.com cgtlive.com/view/spur-therapeutics-gene-therapy-sbt101-generally-well-tolerated-phase-1-trial-adrenoleukodystrophy

Spur Therapeutics' Gene Therapy SBT101 Generally Well ... Initial safety results from the PROPEL trial evaluating SBT101 as a potential gene therapy for spinal cord disease in adult males with x ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11550353/

An in vitro and in vivo efficacy evaluation of gene therapy ... SBT101 was well tolerated, with no observed SBT101-related mortality or clinical signs. These findings not only provide preclinical efficacy data for SBT101 but ...

8. asgct.careboxhealth.com asgct.careboxhealth.com/en-US/trial/listing/495075

A Study to Evaluate Administration of SBT101 Gene Therapy ... This is a Phase 1/2 randomized, blinded, dose-escalation study to evaluate the safety and efficacy of intrathecal (IT) administration of ...