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.

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.

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