Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia

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

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.

Study Overview

• Status: Completed
• Conditions: Dysphonia Resulting From Vocal Fold Scarring; Age-related Dysphonia
• Intervention / Treatment: Biological: Azficel-T (autologous fibroblasts); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Surgery/Head and Neck, David Geffen School of Medicine at UCLA
    • Stanford, California, United States, 94305-5328
      • Dept of Otolaryngology, Stanford Univ Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) before treatment
2. Subject is at least 18 years of age
3. Subject has presence of unilateral or bilateral vocal fold scarring or age-related dysphonia, as diagnosed by medical history and physical examination
4. Subject must have Grade 1-2 mucosal waves as determined by videostroboscopy
5. 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
6. Subject feels that their voice quality is a major handicap
7. 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
8. 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
9. Subject must be willing and able to follow study procedures and instructions

Exclusion Criteria:

1. Subject is pregnant or lactating
2. Subject is a smoker
3. Subject has an upper respiratory infection at baseline (subject can be rescheduled after four weeks)
4. Subject is already participating, or has participated in another clinical trial involving therapeutic intervention within 30 days prior to enrollment
5. Subject plans to begin or continue other vocal fold therapies during the course of this study
6. Subject has other concurrent laryngeal pathology including lesions that would require removal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azficel-T (autologous fibroblasts); Azficel-T will be injected into the vocal fold(s) three times at two week intervals.	Biological: Azficel-T (autologous fibroblasts); 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.; Other Names: LAVIV™
Placebo Comparator: Control; Sterile saline will be injected into the vocal fold(s) three times at two week intervals.	Drug: Placebo; Subjects randomized to placebo will receive injections of sterile saline into the vocal fold(s).; Other Names: Sterile saline for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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).	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
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).	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
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.	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
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.	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
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.	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
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.	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
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.	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

Collaborators and Investigators

• Sponsor: Castle Creek Biosciences, LLC.
• Investigators: Principal Investigator: Dinesh Chhetri, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: March 21, 2014
• First Submitted That Met QC Criteria: April 21, 2014
• First Posted (Estimate): April 23, 2014

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Fibrosis; Laryngeal Diseases; Voice Disorders; Cicatrix; Dysphonia; Hoarseness
• Other Study ID Numbers: FI-V-002