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

• ClinicalTrials.gov Identifier: NCT02132130
• Recruitment Status: Recruiting
• First Posted: May 7, 2014
• Last Update Posted: August 30, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The goal of the study is 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).

Condition or disease	Intervention/treatment	Phase
Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss	Drug: CGF166	Phase 1; Phase 2

Detailed Description:

The study will evaluate 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 are required to have documented, non-fluctuating hearing loss. Part A and Part B enrollment is complete. Part C enrollment is open.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Three-part, Multicenter, Open Label, Single Dose Study to Assess the Safety, Tolerability, and Efficacy of Intra Labyrinthine (IL) CGF166 in Patients With Severe-to-profound Hearing Loss
• Actual Study Start Date: June 23, 2014
• Estimated Primary Completion Date: October 9, 2019
• Estimated Study Completion Date: October 9, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: CGF166 dose 20 uL; single dose volume #1	Drug: CGF166; CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 30 and 40 uL; single dose volume #2	Drug: CGF166; CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 40 uL; single dose volume #3	Drug: CGF166; CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 60 uL; single dose volume #4	Drug: CGF166; CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CFG166 dose 30 uL; Single dose volume #5	Drug: CGF166; CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion

Outcome Measures

Primary Outcome Measures :

1. Number of patients reported adverse events [ Time Frame: 24 months ]
   Number of patients reported with total adverse events, serious adverse events and death as an assessment of safety and tolerability
2. Change in pure tone audiometry compared to pretreatment values [ Time Frame: 24 months ]
   Sensory thresholds at pure tone frequencies from 0.125 KHz through 16 KHz will be measured using standard audiometric techniques.

Secondary Outcome Measures :

1. Change in brainstem auditory evoked responses (BAER) compared to pretreatment values [ Time Frame: 24 months ]
   BAERs will be assessed with standard techniques for clinically significant threshold improvements compared to baseline levels.
2. effects of CGF166 on various assessments of vestibular function compared to pretreatment values [ Time Frame: 24 months ]
   Assessments of the vestibular organs for clinically relevant functional improvement
3. Changes in auditory functions (speech recognition) and vestibular functions before and after IL infusion of CGF166 between the study ear and the contralateral ear [ Time Frame: 24 months ]
   Clinically signficant speech recognition improvement (word and/or sentence) following treatment

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

6. 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

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; trialandresults.registries@novartis.com

Contact: Novartis Pharmaceuticals

Locations

United States, Kansas

Novartis Investigative Site; Recruiting

Kansas City, Kansas, United States, 66160

Contact: Bryan Humphrey 913-588-3759 bhumphrey@kumc.edu

Contact: Kevin Sykes 9135887154 ksykes@kumc.edu

Principal Investigator: Hinrich Staecker, MD

United States, Maryland

Novartis Investigative Site; Completed

Baltimore, Maryland, United States, 21287

United States, New York

Novartis Investigative Site; Active, not recruiting

New York, New York, United States, 10032

United States, Oregon

Novartis Investigative Site; Recruiting

Portland, Oregon, United States, 97239

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Plontke SK. Otology Jubilee: 150 years of the Archiv für Ohrenheilkunde "Where do we come from?--Where are we?--Where are we going?". Eur Arch Otorhinolaryngol. 2015 Jun;272(6):1301-3. doi: 10.1007/s00405-015-3538-4. Epub 2015 Feb 18.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02132130 History of Changes
• Other Study ID Numbers: CCGF166X2201
• First Posted: May 7, 2014
• Last Update Posted: August 30, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

gene therapy; unilateral hearing loss; bilateral hearing loss; balance; vestibular; cochlear implant; hearing restoration

Additional relevant MeSH terms:

Hearing Loss; Deafness; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms