Back to resultsControlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia
Primary Purpose
Dysphonia Resulting From Vocal Fold Scarring, Age-related Dysphonia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Azficel-T (autologous fibroblasts)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Dysphonia Resulting From Vocal Fold Scarring
Eligibility Criteria
Inclusion Criteria:
- Subject has read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) before treatment
- Subject is at least 18 years of age
- Subject has presence of unilateral or bilateral vocal fold scarring or age-related dysphonia, as diagnosed by medical history and physical examination
- Subject must have Grade 1-2 mucosal waves as determined by videostroboscopy
- Subject has failed any one or more of the following treatments including, but not limited to, anti-reflux regimen, speech therapy, or vocal fold injection augmentation prior to screening
- Subject feels that their voice quality is a major handicap
- Subject must have a blood sample tested and found to be non-reactive for human immunodeficiency virus-1 (HIV-1) antibody, hepatitis B surface antigen and hepatitis C virus (HCV) antibody
- If the subject is female and of childbearing potential, she must agree to use a medically acceptable means of birth control, and test negative on a urine pregnancy test
- Subject must be willing and able to follow study procedures and instructions
Exclusion Criteria:
- Subject is pregnant or lactating
- Subject is a smoker
- Subject has an upper respiratory infection at baseline (subject can be rescheduled after four weeks)
- Subject is already participating, or has participated in another clinical trial involving therapeutic intervention within 30 days prior to enrollment
- Subject plans to begin or continue other vocal fold therapies during the course of this study
- Subject has other concurrent laryngeal pathology including lesions that would require removal
Sites / Locations
- Surgery/Head and Neck, David Geffen School of Medicine at UCLA
- Dept of Otolaryngology, Stanford Univ Medical Center
- NYU Langone Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Azficel-T (autologous fibroblasts)
Control
Arm Description
Azficel-T will be injected into the vocal fold(s) three times at two week intervals.
Sterile saline will be injected into the vocal fold(s) three times at two week intervals.
Outcomes
Primary Outcome Measures
Number of Participants With Any Improvement From Baseline in Mucosal Wave Grade
Any improvement from baseline in mucosal wave grade using videostrobscopy to assess the pliability of vocal folds which is visualized as mucosal waves on the vocal fold surface while a participant is phonating a sustained vowel sound.
Number of Participants With an Absolute Change in Voice Handicap Index Score (Decrease of 18 or More Points) From Baseline
Absolute change (decrease by 18 or more points) from baseline in the Voice Handicap Index (VHI) score 4 months after the final treatment.
The VHI is a 30-item test with 10 items in 3 subscales: emotional, physical, and functional. Each item is scored on a 5-point scale: "0" indicating the subject never felt this about the voice problem and "4" indicating the subject always felt this to be the case. An 8-point difference on any subscale (sub-scale range 0-40, higher values represent worse outcomes) has been found to be significant, as was an 18-point difference in the total VHI score (Total scale range 0-120, higher values represent worse outcomes).
Mean Percentage Change From Baseline in Voice Handicap Index Score
Mean percentage change from baseline in the Voice Handicap Index (VHI) score 4 months after the final treatment. The VHI is a 30-item test with 10 items in 3 subscales: emotional, physical, and functional. Each item is scored on a 5-point scale: "0" indicating the subject never felt this about the voice problem and "4" indicating the subject always felt this to be the case. An 8-point difference on any subscale (sub-scale range 0-40, higher values represent worse outcomes) has been found to be significant, as was an 18-point difference in the total VHI score (Total scale range 0-120, higher values represent worse outcomes).
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Dysphonia Using GRBAS Scale.
Perceptual analysis of dysphonia using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Roughness Using GRBAS Scale.
Perceptual analysis of roughness using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Breathiness Using GRBAS Scale.
Perceptual analysis of breathiness using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Asthenia Using GRBAS Scale.
Perceptual analysis of asthenia using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Strain Using GRBAS Scale.
Perceptual analysis of strain using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Secondary Outcome Measures
Full Information
NCT ID
NCT02120781
First Posted
March 21, 2014
Last Updated
May 10, 2021
Sponsor
Castle Creek Biosciences, LLC.
1. Study Identification
Unique Protocol Identification Number
NCT02120781
Brief Title
Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia
Official Title
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for the Treatment of Vocal Fold Scarring and Age-Related Dysphonia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
December 21, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Castle Creek Biosciences, LLC.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objectives of this study are to assess the safety of azficel-T treatment for dysphonia related to vocal fold function and to evaluate the efficacy of azficel-T for the treatment of dysphonia related to vocal fold function.
Detailed Description
Twenty subjects with dysphonia caused by vocal fold scarring or age-related dysphonia will be randomized for treatment with autologous cultured fibroblasts (azficel-T, n=14) or placebo (saline, n=6). Subjects will receive treatment to the vocal fold(s) in the lamina propria compartment.
Subjects with both unilateral and bilateral vocal fold scarring will be treated in this study. Only one vocal fold will be treated at each treatment session alternating to the opposite vocal fold (if applicable) at the next treatment. Subjects are to receive a total of three treatments with study drug (azficel-T or placebo) if one vocal fold is to be treated and up to a total of six treatments with study drug (azficel-T or placebo) if two vocal folds are to be treated at approximately 2-week intervals. Follow-up examinations will be performed at 1, 4, 8, and 12 months after the final treatment. If there are any evident safety issues, follow-up treatments will be delayed or withheld.
In the Blinded Phase of the study, subjects will be followed for safety and efficacy for 4 months after the final treatment. After all subjects have completed the 4-month follow-up visit, the study will be unblinded and subjects will continue to be followed for safety for 12 months after the final treatment. Efficacy assessments will be made through the 12-month follow-up visit in order to document any duration of effect. All AEs that have an onset date from biopsy through the 4-month follow-up visit will be recorded.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dysphonia Resulting From Vocal Fold Scarring, Age-related Dysphonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Azficel-T (autologous fibroblasts)
Arm Type
Experimental
Arm Description
Azficel-T will be injected into the vocal fold(s) three times at two week intervals.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Sterile saline will be injected into the vocal fold(s) three times at two week intervals.
Intervention Type
Biological
Intervention Name(s)
Azficel-T (autologous fibroblasts)
Other Intervention Name(s)
LAVIV™
Intervention Description
Autologous fibroblasts will be cultured from three 3-mm post auricular punch biopsies. Biopsies will be shipped from the clinical sites to the Fibrocell manufacturing site where the cells will be harvested, tested for sterility, endotoxin level, cell identity, viability and concentration. When the desired cell number is reached, cells will be transported to the investigative site as a suspension in shipping media.
Depending upon the clinical circumstances for each subject, the vocal fold(s) will be injected transorally or percutaneously in order to deposit 1.0 mL of study drug into the lamina propria layer of each vocal fold. The injection process will be visualized via a flexible fiberoptic laryngoscope inserted through the nostril.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sterile saline for injection
Intervention Description
Subjects randomized to placebo will receive injections of sterile saline into the vocal fold(s).
Primary Outcome Measure Information:
Title
Number of Participants With Any Improvement From Baseline in Mucosal Wave Grade
Description
Any improvement from baseline in mucosal wave grade using videostrobscopy to assess the pliability of vocal folds which is visualized as mucosal waves on the vocal fold surface while a participant is phonating a sustained vowel sound.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With an Absolute Change in Voice Handicap Index Score (Decrease of 18 or More Points) From Baseline
Description
Absolute change (decrease by 18 or more points) from baseline in the Voice Handicap Index (VHI) score 4 months after the final treatment.
The VHI is a 30-item test with 10 items in 3 subscales: emotional, physical, and functional. Each item is scored on a 5-point scale: "0" indicating the subject never felt this about the voice problem and "4" indicating the subject always felt this to be the case. An 8-point difference on any subscale (sub-scale range 0-40, higher values represent worse outcomes) has been found to be significant, as was an 18-point difference in the total VHI score (Total scale range 0-120, higher values represent worse outcomes).
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Mean Percentage Change From Baseline in Voice Handicap Index Score
Description
Mean percentage change from baseline in the Voice Handicap Index (VHI) score 4 months after the final treatment. The VHI is a 30-item test with 10 items in 3 subscales: emotional, physical, and functional. Each item is scored on a 5-point scale: "0" indicating the subject never felt this about the voice problem and "4" indicating the subject always felt this to be the case. An 8-point difference on any subscale (sub-scale range 0-40, higher values represent worse outcomes) has been found to be significant, as was an 18-point difference in the total VHI score (Total scale range 0-120, higher values represent worse outcomes).
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Dysphonia Using GRBAS Scale.
Description
Perceptual analysis of dysphonia using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Roughness Using GRBAS Scale.
Description
Perceptual analysis of roughness using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Breathiness Using GRBAS Scale.
Description
Perceptual analysis of breathiness using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Asthenia Using GRBAS Scale.
Description
Perceptual analysis of asthenia using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
Title
Number of Participants With at Least One Level of Improvement in Perceptual Analysis of Strain Using GRBAS Scale.
Description
Perceptual analysis of strain using the Grade of Dysphonia, Roughness, Breathiness, Asthenia, Strain (GRBAS) scale is assessed by a blinded voice clinician 4 months after the final treatment. The voice clinician considers pre- and post-treatment voice recordings, and categorizes the individual parameters on the GRBAS scale (absent, mild, moderate, and severe). Scores of mild, moderate, or severe represent increasingly worse outcomes than a score of absent.
Time Frame
Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject has read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) before treatment
Subject is at least 18 years of age
Subject has presence of unilateral or bilateral vocal fold scarring or age-related dysphonia, as diagnosed by medical history and physical examination
Subject must have Grade 1-2 mucosal waves as determined by videostroboscopy
Subject has failed any one or more of the following treatments including, but not limited to, anti-reflux regimen, speech therapy, or vocal fold injection augmentation prior to screening
Subject feels that their voice quality is a major handicap
Subject must have a blood sample tested and found to be non-reactive for human immunodeficiency virus-1 (HIV-1) antibody, hepatitis B surface antigen and hepatitis C virus (HCV) antibody
If the subject is female and of childbearing potential, she must agree to use a medically acceptable means of birth control, and test negative on a urine pregnancy test
Subject must be willing and able to follow study procedures and instructions
Exclusion Criteria:
Subject is pregnant or lactating
Subject is a smoker
Subject has an upper respiratory infection at baseline (subject can be rescheduled after four weeks)
Subject is already participating, or has participated in another clinical trial involving therapeutic intervention within 30 days prior to enrollment
Subject plans to begin or continue other vocal fold therapies during the course of this study
Subject has other concurrent laryngeal pathology including lesions that would require removal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dinesh Chhetri, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
Surgery/Head and Neck, David Geffen School of Medicine at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Dept of Otolaryngology, Stanford Univ Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5328
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
21287562
Citation
Chhetri DK, Berke GS. Injection of cultured autologous fibroblasts for human vocal fold scars. Laryngoscope. 2011 Apr;121(4):785-92. doi: 10.1002/lary.21417. Epub 2011 Feb 1.
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Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia
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