Bilateral Nasolabial Fold Wrinkles
Conditions
Keywords
Treatment of moderate to severe bilateral nasolabial fold wrinkles
Brief summary
The purpose of this study is to evaluate the safety profile and the treatment effect of Isolagen TherapyTM compared with placebo when administered to bilateral nasolabial fold wrinkles.
Interventions
BIOLOGICALAutologous Human Fibroblast (azficel-T)
1. Collection of 3 mm post auricular skin punch biopsies. 2. Three injection treatments administered 5 ± 1 weeks apart on each side of the face.
BIOLOGICALPlacebo
1. Collection of 3 mm post auricular skin punch biopsies. 2. Three injection visits administered 5 ± 1 weeks apart on each side of the face.
Sponsors
Castle Creek Biosciences, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is at least 18 years of age * Level of severity of bilateral nasolabial fold wrinkles meeting severity criteria as per protocol * Level of subject dissatisfaction with both nasolabial fold wrinkles as per protocol * Ability to comply with the study requirements * Negative pregnancy test (Females) * Healthy post-auricular skin for biopsy
Exclusion criteria
* Excessive dermatochalasis of the treatment area * Inability to lessen the nasolabial fold wrinkles by physically spreading the area apart * Total area to be treated exceeds 20 cm in length * Physical attributes which may prevent assessment or treatment as judged by the evaluator * Use of an investigational product/procedure within 30 days prior to enrollment or plans for use during the study * Previous treatment with the sponsor's product * History of active autoimmune disease or organ transplantation * Diagnosis of cancer, unless successfully treated or in remission (basal cell carcinoma is excluded) * Active or chronic skin disease * Known genetic disorders affecting fibroblasts or collagen * Active systemic infection * Requires chronic antibiotic or steroidal therapy * Use of certain commercial products/procedures to the treatment area prior to study enrollment or plans for use during the study * Use of systemic agents that increase bleeding or clotting, or disorders equated with these effects * Known allergic reactions to agents used in preparation of treatment * Excessive exposure to sun without adequate sun protection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject Wrinkle Assessment Responders | Baseline (prior to first treatment) and 6 months post final treatment | A two point improvement on the Subject's live assessment of the wrinkles of the lower part of the face as compared to baseline on the Subject Wrinkle Assessment was considered a responder. The Subject Wrinkle Assessment scale was a five point scale with a score of -2 (Very Dissatisfied) being the worst and a score of +2 (Very Satisfied) being the best. |
| Evaluator Wrinkle Severity Assessment Responders | Baseline (prior to first treatment) and 6 months after last treatment | A responder was defined as a two point improvement on the blinded Evaluator's live assessment of each of the bilateral nasolabial fold wrinkles at rest using the 6-point ordinal Lemperle Wrinkle Severity Scale. On the Lemperle scale, a score of 5 (Very Deep Wrinkle) is worst and a score of 0 (No Visible Wrinkle) is best. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Wrinkle Assessment Responders | Baseline (prior to first treatment) compared to 3rd treatment visit, 2 and 4 months post final treatment | A two point improvement on the Subject's live assessment of the wrinkles of the lower part of the face as compared to baseline on the Subject Wrinkle Assessment was considered a responder. The Subject Wrinkle Assessment scale was a five point scale with a score of -2 (Very Dissatisfied) being the worst and a score of +2 (Very Satisfied) being the best. |
| Evaluator Wrinkle Severity Assessment Responders | Baseline (prior to first treatment) compared to 3rd treatment visit, 2 and 4 months post final treatment | A responder was defined as a two point improvement on the blinded Evaluator's live assessment of each of the bilateral nasolabial fold wrinkles at rest using the 6-point ordinal Lemperle Wrinkle Severity Scale. On the Lemperle scale, a score of 5 (Very Deep Wrinkle) is worst and a score of 0 (No Visible Wrinkle) is best. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited between October 23, 2006 and February 9, 2007.
Pre-assignment details
Patients were enrolled and biopsied for manufacture of study product. All randomized patients were included in the Intent to Treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Autologous Fibroblasts Patients treated with autologous dermal fibroblasts | 100 |
| Placebo Patients treated with placebo solution | 103 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Insufficient manufacturing yield | 5 | 1 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 6 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Autologous Fibroblasts | Total | Placebo |
|---|---|---|---|
| Age Continuous | 57.5 years STANDARD_DEVIATION 8.32 | 56.7 years STANDARD_DEVIATION 8.12 | 55.9 years STANDARD_DEVIATION 7.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 17 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 186 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 94 Participants | 193 Participants | 99 Participants |
| Region of Enrollment United States | 100 participants | 203 participants | 103 participants |
| Sex: Female, Male Female | 88 Participants | 182 Participants | 94 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 100 | 34 / 103 |
| serious Total, serious adverse events | 2 / 100 | 4 / 103 |
Outcome results
Primary
Evaluator Wrinkle Severity Assessment Responders
A responder was defined as a two point improvement on the blinded Evaluator's live assessment of each of the bilateral nasolabial fold wrinkles at rest using the 6-point ordinal Lemperle Wrinkle Severity Scale. On the Lemperle scale, a score of 5 (Very Deep Wrinkle) is worst and a score of 0 (No Visible Wrinkle) is best.
Time frame: Baseline (prior to first treatment) and 6 months after last treatment
Population: Analysis population was the ITT population, defined as all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous Fibroblast | Evaluator Wrinkle Severity Assessment Responders | 33 participants |
| Placebo | Evaluator Wrinkle Severity Assessment Responders | 7 participants |
Comparison: A 5% level of significance was used as the threshold for determination of statistical significance, and all tests were two-tailed. the effect size and associated 95% confidence interval (CI) are provided for all comparative efficacy outcomes. Primary analysis of the two co-primary efficacy endpoints and the secondary efficacy endpoints were performed on the ITT population.p-value: <0.00001Cochran-Mantel-Haenszel
Primary
Subject Wrinkle Assessment Responders
A two point improvement on the Subject's live assessment of the wrinkles of the lower part of the face as compared to baseline on the Subject Wrinkle Assessment was considered a responder. The Subject Wrinkle Assessment scale was a five point scale with a score of -2 (Very Dissatisfied) being the worst and a score of +2 (Very Satisfied) being the best.
Time frame: Baseline (prior to first treatment) and 6 months post final treatment
Population: Analysis population was the ITT population, defined as all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous Fibroblast | Subject Wrinkle Assessment Responders | 57 participants |
| Placebo | Subject Wrinkle Assessment Responders | 31 participants |
Comparison: A 5% level of significance was used as the threshold for determination of statistical significance, and all tests were two-tailed. the effect size and associated 95% confidence interval (CI) are provided for all comparative efficacy outcomes. Primary analysis of the two co-primary efficacy endpoints and the secondary efficacy endpoints were performed on the ITT population.p-value: 0.00001Cochran-Mantel-Haenszel
Secondary
Evaluator Wrinkle Severity Assessment Responders
A responder was defined as a two point improvement on the blinded Evaluator's live assessment of each of the bilateral nasolabial fold wrinkles at rest using the 6-point ordinal Lemperle Wrinkle Severity Scale. On the Lemperle scale, a score of 5 (Very Deep Wrinkle) is worst and a score of 0 (No Visible Wrinkle) is best.
Time frame: Baseline (prior to first treatment) compared to 3rd treatment visit, 2 and 4 months post final treatment
Population: Analysis population was the ITT population, defined as all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Autologous Fibroblast | Evaluator Wrinkle Severity Assessment Responders | Responders at 3rd Treatment | 14 participants |
| Autologous Fibroblast | Evaluator Wrinkle Severity Assessment Responders | Responders - 2 months Post Final Treatment | 28 participants |
| Autologous Fibroblast | Evaluator Wrinkle Severity Assessment Responders | Responders - 4 months Post Final Treatment | 27 participants |
| Placebo | Evaluator Wrinkle Severity Assessment Responders | Responders at 3rd Treatment | 5 participants |
| Placebo | Evaluator Wrinkle Severity Assessment Responders | Responders - 2 months Post Final Treatment | 10 participants |
| Placebo | Evaluator Wrinkle Severity Assessment Responders | Responders - 4 months Post Final Treatment | 9 participants |
Secondary
Subject Wrinkle Assessment Responders
A two point improvement on the Subject's live assessment of the wrinkles of the lower part of the face as compared to baseline on the Subject Wrinkle Assessment was considered a responder. The Subject Wrinkle Assessment scale was a five point scale with a score of -2 (Very Dissatisfied) being the worst and a score of +2 (Very Satisfied) being the best.
Time frame: Baseline (prior to first treatment) compared to 3rd treatment visit, 2 and 4 months post final treatment
Population: Analysis population was the ITT population, defined as all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Autologous Fibroblast | Subject Wrinkle Assessment Responders | Responders at 3rd Treatment | 38 participants |
| Autologous Fibroblast | Subject Wrinkle Assessment Responders | Responders - 2 months Post Final Treatment | 49 participants |
| Autologous Fibroblast | Subject Wrinkle Assessment Responders | Responders - 4 months Post Final Treatment | 48 participants |
| Placebo | Subject Wrinkle Assessment Responders | Responders at 3rd Treatment | 23 participants |
| Placebo | Subject Wrinkle Assessment Responders | Responders - 2 months Post Final Treatment | 25 participants |
| Placebo | Subject Wrinkle Assessment Responders | Responders - 4 months Post Final Treatment | 26 participants |