Safety and Efficacy Study of Isolagen Therapy in the Treatment of Nasolabial Fold Wrinkles
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active
|
Biological: Autologous Human Fibroblasts (azficel-T)
Collection of 3 mm post auricular skin punch biopsies.
Three treatment visits with injections administered 5 ± 1 weeks apart on each side of the face.
Other Names:
|
| Placebo Comparator: Placebo
|
Biological: Placebo
Collection of 3 mm post auricular skin punch biopsies.
Three treatment visits with injections administered 5 ± 1 weeks apart on each side of the face.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Brighton Medical Corporation | Beverly Hills | California | United States | 91210 |
| 2 | Therapeutics Clinical Research | San Diego | California | United States | 92123 |
| 3 | Gwinnett Clinical Research Center | Snellville | Georgia | United States | 30078 |
| 4 | Dermatology San Antonio | San Antonio | Texas | United States | 78229 |
| 5 | Charlottesville Medical Research | Charlottesville | Virginia | United States | 22911 |
| 6 | Institute of Anti Aging Research | Virginia Beach | Virginia | United States | 23454 |
Sponsors and Collaborators
- Castle Creek Biosciences, LLC.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IT-R-006
Study Results
Participant Flow
| Recruitment Details | Patients were recruited between 1 November 2006 to 27 January 2007 |
|---|---|
| Pre-assignment Detail | Patients were enrolled and biopsied for manufacture of study product. All randomized patients were included in the Intent to Treat (ITT) population. |
| Arm/Group Title | Autologous Fibroblasts | Placebo |
|---|---|---|
| Arm/Group Description | Patients treated with autologous dermal fibroblasts | Patients treated with placebo solution |
| Period Title: Overall Study | ||
| STARTED | 110 | 108 |
| COMPLETED | 93 | 98 |
| NOT COMPLETED | 17 | 10 |
Baseline Characteristics
| Arm/Group Title | Autologous Fibroblasts | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Patients treated with autologous dermal fibroblasts | Patients treated with placebo solution | Total of all reporting groups |
| Overall Participants | 110 | 108 | 218 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
53.9
(10.38)
|
55.4
(9.42)
|
54.6
(9.92)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
103
93.6%
|
95
88%
|
198
90.8%
|
| Male |
7
6.4%
|
13
12%
|
20
9.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
12
10.9%
|
12
11.1%
|
24
11%
|
| Not Hispanic or Latino |
98
89.1%
|
96
88.9%
|
194
89%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
0.9%
|
1
0.9%
|
2
0.9%
|
| White |
98
89.1%
|
95
88%
|
193
88.5%
|
| More than one race |
11
10%
|
12
11.1%
|
23
10.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
110
100%
|
108
100%
|
218
100%
|
Outcome Measures
| Title | Subject Wrinkle Assessment Responders |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was the ITT population, defined as all randomized subjects. |
| Arm/Group Title | Autologous Fibroblasts | Placebo |
|---|---|---|
| Arm/Group Description | Patients treated with autologous fibroblasts (azficel-T). | Patients treated with placebo solution. |
| Measure Participants | 110 | 108 |
| Number [participants] |
50
45.5%
|
19
17.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Autologous Fibroblasts, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.00001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by combined treatment site. | |
| Title | Evaluator Wrinkle Severity Assessment Responders |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was the ITT population, defined as all randomized subjects. |
| Arm/Group Title | Autologous Fibroblasts | Placebo |
|---|---|---|
| Arm/Group Description | Patients treated with autologous fibroblasts (azficel-T). | Patients treated with placebo solution. |
| Measure Participants | 110 | 108 |
| Number [participants] |
21
19.1%
|
8
7.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Autologous Fibroblasts, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | .0075 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by combined treatment site. | |
| Title | Subject Wrinkle Assessment Responders |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was the ITT population, defined as all randomized subjects. |
| Arm/Group Title | Autologous Fibroblasts | Placebo |
|---|---|---|
| Arm/Group Description | Patients treated with autologous fibroblasts (azficel-T). | Patients treated with placebo solution. |
| Measure Participants | 110 | 108 |
| Visit 3 |
34
30.9%
|
20
18.5%
|
| Visit 4 |
51
46.4%
|
25
23.1%
|
| Visit 5 |
47
42.7%
|
24
22.2%
|
| Title | Evaluator Wrinkle Severity Assessment Responders |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was the ITT population, defined as all randomized subjects. |
| Arm/Group Title | Autologous Fibroblasts | Placebo |
|---|---|---|
| Arm/Group Description | Patients treated with autologous fibroblasts (azficel-T). | Patients treated with placebo solution. |
| Measure Participants | 110 | 108 |
| Visit 3 |
17
15.5%
|
4
3.7%
|
| Visit 4 |
22
20%
|
8
7.4%
|
| Visit 5 |
26
23.6%
|
7
6.5%
|
Adverse Events
| Time Frame | Adverse events were collected from the baseline visit through the final study visit, 6 months after final study treatment. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Autologous Fibroblasts | Placebo | ||
| Arm/Group Description | Patients treated with autologous fibroblasts (azficel-T). | Patients treated with placebo solution. | ||
All Cause Mortality |
||||
| Autologous Fibroblasts | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Autologous Fibroblasts | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/98 (8.2%) | 7/99 (7.1%) | ||
| Cardiac disorders | ||||
| Angina Pectoris | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Coronary Artery Disease | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Cardiac Arrest | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Congenital, familial and genetic disorders | ||||
| Spondylolisthesis | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Eye disorders | ||||
| Retinal Detachment | 0/98 (0%) | 0 | 1/99 (1%) | 2 |
| Gastrointestinal disorders | ||||
| Impaired Gastric Emptying | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Infections and infestations | ||||
| Staphylococcal Infection | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Appendicitis | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Cervical Vertebral Fracture | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Rib Fracture | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Spinal Column Stenosis | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Muscular Weakness | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Uterine Leiomyoma | 0/98 (0%) | 0 | 1/99 (1%) | 1 |
| Reproductive system and breast disorders | ||||
| Menorrhagia | 0/98 (0%) | 0 | 2/99 (2%) | 2 |
| Dysmenorrhoea | 1/98 (1%) | 2 | 0/99 (0%) | 0 |
| Endometriosis | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Surgical and medical procedures | ||||
| Nephrectomy | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
| Vascular disorders | ||||
| Subarachnoid Hemorrhage | 1/98 (1%) | 1 | 0/99 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Autologous Fibroblasts | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 32/98 (32.7%) | 33/99 (33.3%) | ||
| General disorders | ||||
| Injection site bruising | 5/98 (5.1%) | 6 | 13/99 (13.1%) | 20 |
| Injection site erythema | 14/98 (14.3%) | 19 | 6/99 (6.1%) | 9 |
| Injection site haemorrhage | 10/98 (10.2%) | 30 | 15/99 (15.2%) | 45 |
| Infections and infestations | ||||
| Upper respiratory tract infection | 8/98 (8.2%) | 8 | 6/99 (6.1%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Publications or presentations by the Investigator or his associates, were required to be submitted to the sponsor for review and approval.
Results Point of Contact
| Name/Title | Kevin Hennegan |
|---|---|
| Organization | CBR International Corp. |
| Phone | 720-746-1190 |
| khennegan@cbrintl.com |
- IT-R-006