Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing LossPhase 1/2NCT02132130
Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss
A Phase 1/2 study testing CGF166 in people with Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss, run by Novartis Pharmaceuticals at 4 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss
- What is being tested?
- CGF166
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesUnited States
- Study dates
- 23 Jun 2014to 9 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- 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
- 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
- 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
Who cannot join
- Patients with hearing loss caused by genetic/developmental disorders, e.g., cochlea aplasia
- 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;
- Patients with a history of cochlear implant in the study ear
- 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
- Patients who will require ototoxic drugs as routine therapy over the course of the study, for example cystic fibrosis patients
- Any contraindication to the planned surgery or anesthesia as determined by the surgeon or anesthesiologist
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- Previous surgery in the study ear
- 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
- Pregnant women
- Abnormal vital signs and/or ECG that suggest potential contraindication for planned study anesthesia
- Past serious adverse reaction to anesthesia
- Meniere's Disease
- History of radiation therapy to the head and neck
- Participation in a clinical trial within the last 30 days
- Immunocompromised patients, as judged by the investigators based on patient history, physical exam and CBC
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Novartis Investigative Site
Baltimore, Maryland, 21287
Novartis Investigative Site
Kansas City, Kansas, 66160
Novartis Investigative Site
New York, New York, 10032
Novartis Investigative Site
Portland, Oregon, 97239
About this study
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
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).
Read the detailed 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.
- Being tested
- CGF166
- Keywords
- gene therapy, unilateral hearing loss, bilateral hearing loss, balance, vestibular, cochlear implant, hearing restoration
- Medical subject headings
- Hearing Loss, Unilateral, Hearing Loss, Bilateral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CGF166Drug
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
| Study group | Role | What they receive |
|---|---|---|
| CGF166 dose 20 uL | Experimental | single dose volume #1 Receives: Drug: CGF166 |
| CGF166 dose 30 and 40 uL | Experimental | single dose volume #2 Receives: Drug: CGF166 |
| CGF166 dose 40 uL | Experimental | single dose volume #3 Receives: Drug: CGF166 |
| CGF166 dose 60 uL | Experimental | single dose volume #4 Receives: Drug: CGF166 |
| CFG166 dose 30 uL | Experimental | Single dose volume #5 Receives: Drug: CGF166 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
AE tables are below in the Adverse Events section of this report.
Measured: week 52
Number of Adverse Events
AE tables are below in the Adverse Events section of this report.
Measured: week 52
Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values
Summary of pure tone audiometry air conduction thresholds at frequency 0.125 KHz
Measured: Days 29, 57, 85, 113, 141, 169, 358, 537, 600
Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency
Summary of pure tone audiometry bone conduction thresholds by time and frequency 0.250 KHz
Measured: Days 29, 57, 85, 113, 141, 169, 358,537, EoS
Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
Summary of change from baseline in pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.
Measured: Week 52
Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
Summary of change from baseline in Non-treated ear's pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.
Measured: Week 52
Secondary outcomes (3)
Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values
BAERs was assessed with standard techniques for clinically significant threshold improvements compared to baseline levels.
Measured: 24 months
Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values
Response in vestibular assessments (Head impulse test (HIT), Vestibular evoked myogenic potential (VEMP), Subjective visual vertical (SVV)) to CGF166.
Measured: 24 months
Number of Participants With Changes in Auditory Functions (Speech Recognition) and Vestibular Functions Before and After IL Infusion of CGF166 Between the Study Ear and the Contralateral Ear
Clinically signficant speech recognition improvement (word and/or sentence) following treatment. The individual auditory assessments were speech audiometry, AzBio sentence test, consonant nucleus consonant test, word recognition, Hearing-in-Noise Test (HINT), Brainstem auditory evoked response evaluations (BAER), Distortion product otoacoustic emission testing (DPOE) and shoebox audiometry.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2014 (estimated)
- Study start23 Jun 2014
- Primary completion9 Dec 2019
- Study completion9 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing LossStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02132130
- Sponsor's protocol ID
- CCGF166X2201
- Status last verified
- Oct 2021
- First submitted
- 5 May 2014
- Last updated
- 8 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Publications
Plontke SK. Otology Jubilee: 150 years of the Archiv fur 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. No abstract available.
PubMed 25690605
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02132130
- Acronym / sponsor ID
- CCGF166X2201
- Keywords
- gene therapy, unilateral hearing loss, bilateral hearing loss, balance, vestibular, cochlear implant, hearing restoration
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2014 (actual)
- Primary completion
- 9 Dec 2019 (actual)
- Study completion
- 9 Dec 2019 (actual)
- First posted
- 7 May 2014 (estimated)
- Results
- Posted 30 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| CGF166 dose 20 uL | Experimental | Drug: CGF166single dose volume #1 |
| CGF166 dose 30 and 40 uL | Experimental | Drug: CGF166single dose volume #2 |
| CGF166 dose 40 uL | Experimental | Drug: CGF166single dose volume #3 |
| CGF166 dose 60 uL | Experimental | Drug: CGF166single dose volume #4 |
| CFG166 dose 30 uL | Experimental | Drug: CGF166Single dose volume #5 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written informed consent must be obtained before any assessment is performed.
- 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:
- 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
- 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
Key exclusion criteria (15 listed)
- Patients with hearing loss caused by genetic/developmental disorders, e.g., cochlea aplasia
- 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;
- Patients with a history of cochlear implant in the study ear
- 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
- Patients who will require ototoxic drugs as routine therapy over the course of the study, for example cystic fibrosis patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CGF166CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion | Drug | CFG166 dose 30 uL, CGF166 dose 20 uL, CGF166 dose 30 and 40 uL, CGF166 dose 40 uL, CGF166 dose 60 uL |
Primary outcome
Number of Participants With Adverse Events
Time frame: week 52
AE tables are below in the Adverse Events section of this report.
Number of Adverse Events
Time frame: week 52
AE tables are below in the Adverse Events section of this report.
Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values
Time frame: Days 29, 57, 85, 113, 141, 169, 358, 537, 600
Summary of pure tone audiometry air conduction thresholds at frequency 0.125 KHz
Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency
Time frame: Days 29, 57, 85, 113, 141, 169, 358,537, EoS
Summary of pure tone audiometry bone conduction thresholds by time and frequency 0.250 KHz
Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
Time frame: Week 52
Summary of change from baseline in pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.
Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
Time frame: Week 52
Summary of change from baseline in Non-treated ear's pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.
3 secondary outcomes
Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values
Time frame: 24 months
Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values
Time frame: 24 months
Number of Participants With 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25690605Plontke SK. Otology Jubilee: 150 years of the Archiv fur 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. No abstract available.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CGF166 in people with Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss, run by Novartis Pharmaceuticals at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (time frame: week 52). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02132130, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.