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

NCT02120781 | Completed Phase 2 Results

• 1 other identifier: FI-V-002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

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.

Conditions

Dysphonia Resulting From Vocal Fold Scarring; Age-related Dysphonia

Outcome Measures

Primary Outcomes (8)

• 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

Study Arms (2)

Azficel-T (autologous fibroblasts)

EXPERIMENTAL

Azficel-T will be injected into the vocal fold(s) three times at two week intervals.

Biological: Azficel-T (autologous fibroblasts)

Control

PLACEBO COMPARATOR

Sterile saline will be injected into the vocal fold(s) three times at two week intervals.

Drug: Placebo

Interventions

Azficel-T (autologous fibroblasts) BIOLOGICAL

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.

Also known as: LAVIV™

Azficel-T (autologous fibroblasts)

Placebo DRUG

Subjects randomized to placebo will receive injections of sterile saline into the vocal fold(s).

Also known as: Sterile saline for injection

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Castle Creek Biosciences, LLC.: lead

Study Sites (3)

Surgery/Head and Neck, David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Dept of Otolaryngology, Stanford Univ Medical Center

Stanford, California, 94305-5328, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Related Publications (1)

• 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.

  PMID: 21287562 BACKGROUND

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Head, Research and Development
• Organization: Castle Creek Biosciences

medinfo@castlecreekbio.com

13128471291

Study Officials

• Dinesh Chhetri, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: April 23, 2014
• Study Start: March 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: December 21, 2016
• Last Updated: June 3, 2021
• Results First Posted: June 3, 2021

Record last verified: 2021-05

Locations

US (3)