In short
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.
At a glance
- 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)
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. 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.
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.
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. Here's how it works:
- The therapy contains the cDNA sequence of the human otoferlin gene (specifically, isoform 5).
- It is delivered directly into the cochlea, the part of the inner ear responsible for hearing.
- Once inside, it aims to restore the expression of the full-length, active human otoferlin protein in the cochlear inner hair cells (IHCs).
- By repairing the otoferlin deficiency, the therapy seeks to restore the patient's hearing.
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. 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
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
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
Children with certain conditions, such as prior cochlear implants or participation in other gene therapy trials, are not eligible for this study.
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.
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
Potential risks:
- Adverse reactions to the therapy
- Complications from the intracochlear injection procedure
- Unknown long-term effects of gene therapy
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.
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.