#1 Clinical Trials Search in Europe

Adeno‐Associated Viral Vector Serotype 8 Containing The 3′ Human Otoferlin Coding Sequence

A groundbreaking clinical trial is underway to evaluate the efficacy and safety of a new gene therapy called SENS-501 for children with severe to profound hearing loss caused by mutations in the Otoferlin gene. This Phase I/II trial aims to restore hearing by using an innovative approach involving the injection of a specially designed viral vector into the cochlea. The study focuses on children aged 6 to 31 months and could potentially offer hope for those affected by this rare genetic condition.

Table of Contents

What is SENS-501?

SENS-501 is an innovative gene therapy product designed to treat severe to profound hearing loss caused by mutations in the otoferlin gene[1]. It is currently being studied in a Phase I/II clinical trial to evaluate its safety and effectiveness in children with this specific type of hearing impairment[1].

The therapy consists of two main components:

  • SENS-501-Nter: An adeno-associated viral vector serotype 8 containing the 5′ human otoferlin coding sequence
  • SENS-501-Cter: An adeno-associated viral vector serotype 8 containing the 3′ human otoferlin coding sequence

These components work together to deliver the complete otoferlin gene to the inner ear cells[1].

How Does SENS-501 Work?

SENS-501 is a gene therapy that aims to restore hearing by addressing the underlying genetic cause of otoferlin deficiency[1]. Here’s how it works:

  1. The therapy contains the cDNA sequence of the human otoferlin gene (specifically, isoform 5).
  2. It is delivered directly into the cochlea, the part of the inner ear responsible for hearing.
  3. Once inside, it aims to restore the expression of the full-length, active human otoferlin protein in the cochlear inner hair cells (IHCs).
  4. By repairing the otoferlin deficiency, the therapy seeks to restore the patient’s hearing[1].

Target Condition: Severe to Profound Hearing Loss

SENS-501 is specifically designed for children with bilateral severe to profound hearing loss due to otoferlin deficiency[1]. This condition is characterized by:

  • Severe to profound hearing loss in both ears
  • Caused by mutations in both copies of the otoferlin gene
  • Presence of outer hair cell function (indicated by otoacoustic emissions or OAEs)
  • Normal cochlear and internal auditory canal structure[1]

Clinical Trial Details

The ongoing clinical trial for SENS-501 is a Phase I/II study with the following characteristics:

  • Trial design: Open-label, dose escalation and expansion study
  • Participants: Children aged 6 to 31 months
  • Main objectives:
    • Part 1: Assess safety and tolerability of SENS-501
    • Part 2: Evaluate the efficacy of SENS-501
  • Secondary objectives: Evaluate the clinical performance, safety, and usability of the SPHYNX Pump and Catheter used for administration[1]

Eligibility Criteria

To participate in the SENS-501 clinical trial, children must meet specific criteria, including:

  • Age between 6 and 31 months at the time of inclusion
  • Severe to profound hearing loss confirmed by ABR (Auditory Brainstem Response)
  • Biallelic mutation in the otoferlin gene
  • Presence of OAEs (Otoacoustic Emissions)
  • Normal cochlear and internal auditory canal structure
  • Intact vestibular function[1]

Children with certain conditions, such as prior cochlear implants or participation in other gene therapy trials, are not eligible for this study[1].

Administration and Dosage

SENS-501 is administered through a unilateral intracochlear injection, meaning it’s injected into one ear. The study is testing two dose levels:

  • Low dose: 1.5 E+11 VG SENS-501-Nter + 1.5 E+11 VG SENS-501-Cter
  • High dose: 4.5 E+11 VG SENS-501-Nter + 4.5 E+11 VG SENS-501-Cter

The therapy is administered as a single dose using a special delivery system consisting of an infusion pump and an intracochlear catheter[1].

Potential Benefits and Risks

While SENS-501 shows promise, it’s important to understand that it’s still in the experimental stage. Potential benefits and risks include:

Potential benefits:

  • Improvement in hearing thresholds
  • Restoration of otoferlin protein function
  • Long-term hearing improvement[1]

Potential risks:

  • Adverse reactions to the therapy
  • Complications from the intracochlear injection procedure
  • Unknown long-term effects of gene therapy[1]

Future Prospects

If successful, SENS-501 could represent a significant breakthrough in treating genetic causes of hearing loss. The therapy has received orphan drug designation (EU/3/22/2698), indicating its potential to address an unmet medical need[1].

As research progresses, SENS-501 may offer hope to children with severe hearing loss due to otoferlin gene mutations, potentially improving their quality of life and communication abilities.

Aspect Details
Trial Name Phase I/II clinical trial with SENS-501
Target Condition Severe to profound hearing loss due to Otoferlin gene mutations
Age Group Children aged 6 to 31 months
Treatment SENS-501 (Adeno-associated viral vector serotype 8 containing human Otoferlin coding sequence)
Administration Single unilateral intracochlear injection
Primary Objectives Assess safety, tolerability, and efficacy of SENS-501
Secondary Objectives Evaluate clinical performance of SPHYNX Pump and Catheter
Key Inclusion Criteria Severe hearing loss, biallelic Otoferlin mutation, presence of OAEs
Key Exclusion Criteria Prior gene therapy, cochlear implant, contraindications to surgery
Primary Endpoints Number of adverse events, improvement in hearing threshold (ABR)

FAQ

  • What is SENS-501 and how does it work? SENS-501 is a gene therapy product containing the cDNA sequence of the human Otoferlin transgene. It aims to restore the expression of the full-length active human Otoferlin protein in the cochlear inner hair cells. This therapy is designed to repair Otoferlin deficiency and potentially restore hearing in patients with severe to profound hearing loss due to Otoferlin gene mutations.
  • Who is eligible for this clinical trial? The trial is open to children aged 6 to 31 months with severe to profound hearing loss due to biallelic mutations in the Otoferlin gene. Participants must have intact vestibular function and documented normal cochlea and internal auditory canals. They should not have received previous gene therapy or have a cochlear implant.
  • How is the treatment administered? The treatment involves a single administration of SENS-501 through unilateral intracochlear injection. This means the therapy is injected directly into one ear using a special injection system that includes an infusion pump and an intracochlear catheter.
  • What are the main objectives of the trial? The main objectives are to assess the safety and tolerability of SENS-501 in Part 1 of the trial, and to evaluate its efficacy in improving hearing thresholds in Part 2. The study will also assess the clinical performance, safety, and usability of the SPHYNX Pump and Catheter used for administration.
  • What are the potential benefits and risks of participating in this trial? The potential benefit is the possibility of improved hearing for children with severe hearing loss due to Otoferlin deficiency. However, as with any clinical trial, there are risks involved, including potential adverse events related to the treatment or the administration procedure. The trial is designed to carefully monitor and assess these risks throughout the study period.

Ongoing Clinical Trials on Adeno‐Associated Viral Vector Serotype 8 Containing The 3′ Human Otoferlin Coding Sequence

Unfortunately, we did not find any clinical trials matching the selected criteria. Try changing the filter settings or broadening the search criteria to see more available research participation opportunities.

Glossary

  • Otoferlin: A protein essential for hearing that plays a crucial role in the function of inner hair cells in the cochlea. Mutations in the Otoferlin gene can lead to severe to profound hearing loss.
  • Gene therapy: A technique that uses genes to treat or prevent disease. In this case, it involves introducing genetic material to correct the function of the mutated Otoferlin gene.
  • Adeno-associated viral vector: A tool used in gene therapy to deliver genetic material into cells. It's derived from a virus but modified to be safe and non-pathogenic.
  • Intracochlear injection: A procedure where a substance is injected directly into the cochlea, the snail-shaped part of the inner ear responsible for hearing.
  • ABR (Auditory Brainstem Response): A test used to measure hearing sensitivity and neural function in the auditory pathway.
  • OAEs (Otoacoustic Emissions): Sounds generated by the inner ear, often used to assess cochlear function and hearing sensitivity.
  • Biallelic mutation: A genetic condition where mutations are present in both copies of a gene, one inherited from each parent.
  • Vestibular function: The body's balance system, located in the inner ear, which helps maintain equilibrium and spatial orientation.
  • Cochlea: The spiral-shaped part of the inner ear that converts sound vibrations into nerve impulses sent to the brain.
  • PTA (Pure Tone Audiometry): A hearing test that measures the softest sounds a person can hear at different frequencies.

References

  1. http://clinicaltrials.eu/trial/study-on-sens-501-for-children-with-severe-hearing-loss-due-to-otoferlin-gene-mutations/