Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss

Treatments: Drug: CGF166

Study type: Interventional

Funder types: Industry

Identifiers

NCT02132130

CCGF166X2201

Details and patient eligibility

About

The goal of the study was to evaluate the safety, tolerability, and the potential ability of CGF166 delivered through IL-infusion to improve hearing. CGF166 is a recombinant adenovirus 5 (Ad5) vector containing a cDNA encoding the human Atonal transcription factor (Hath1).

Full description

This study evaluated the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients were required to have documented, non-fluctuating hearing loss.

Enrollment: 22 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For all Parts A, B and C of the study,

Inclusion criteria:

1. Written informed consent must be obtained before any assessment is performed.

2. For all Parts A, B and C of the study, male or female patients, 18 to 75 years old, inclusive, with severe-to-profound bilateral hearing loss or unilateral hearing loss with intact vestibular function in the nonoperative ear. Non-fluctuating severe-to-profound hearing loss is required for the study ear and is defined as:

   • PTA within 10 dB of the PTA obtained at least 11 months previously.
   • Word recognition within 20% of previous test at least 11 months previously

3. Candidate ear ("study ear"): Minimal residual hearing based on the pure tone average of 0.5, 1, 2, and 4 kHz thresholds of ≤110 dB HL

4. Candidate ear ("study ear"): Pure tone audiometric thresholds of ≥50 dB HL for each testable octave frequency of 0.125 and 0.250 kHz, ≥70 dB HL for each testable octave frequency from 0.5 through 8 kHz and sentence recognition scores ≤50% at screening.

5. Patients with intact vestibular function in at least one ear (non-study ear) as measured by vestibular evoked myogenic potential (VEMP) 7. Able to communicate well with the investigator, to understand and comply with the requirements of the study 8. MRI scan within 6 months or at screening to confirm suitability for inner ear surgery 9. Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) <45 kg/m2. BMI = Body weight (kg) / [Height (m)]2

Exclusion Criteria:

1. Patients with hearing loss caused by genetic/developmental disorders, e.g., cochlea aplasia
2. Patients with existing conductive hearing loss or mixed hearing loss as judged by the Principal Investigator following a thorough review of all of the trial hearing assessments;
3. Patients with a history of cochlear implant in the study ear
4. Hearing loss due to any other cause that would not be expected to respond to hair cell regeneration, for example mechanical trauma or central auditory lesions or lack of an auditory nerve
5. Patients who will require ototoxic drugs as routine therapy over the course of the study, for example cystic fibrosis patients
6. Any contraindication to the planned surgery or anesthesia as determined by the surgeon or anesthesiologist
7. Previous surgery in the study ear
8. Any otological history, such as chronic otitis, cholesteatoma, tympanic membrane perforation, that suggests poor candidacy for cochlear implant or inner ear surgery or suggests potential interference with study auditory or vestibular function tests
9. Pregnant women
10. Abnormal vital signs and/or ECG that suggest potential contraindication for planned study anesthesia
11. Past serious adverse reaction to anesthesia
12. Meniere's Disease
13. History of radiation therapy to the head and neck
14. Participation in a clinical trial within the last 30 days
15. Immunocompromised patients, as judged by the investigators based on patient history, physical exam and CBC

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 5 patient groups

CGF166 dose 20 uL

Experimental group

Description:

single dose volume #1

Treatment:

Drug: CGF166

CGF166 dose 30 and 40 uL

Experimental group

Description:

single dose volume #2

Treatment:

Drug: CGF166

CGF166 dose 40 uL

Experimental group

Description:

single dose volume #3

Treatment:

Drug: CGF166

CGF166 dose 60 uL

Experimental group

Description:

single dose volume #4

Treatment:

Drug: CGF166

CFG166 dose 30 uL

Experimental group

Description:

Single dose volume #5

Treatment:

Drug: CGF166