Pilot Study of Azficel-T for the Treatment of Restrictive Burn Scars

• Sponsor: Castle Creek Biosciences, LLC. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01858753
• Collaborator: (none)
• Enrollment: 5
• Locations: 9
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This Phase II, double-blind, randomized, placebo-controlled pilot study is designed to determine whether injection of autologous fibroblasts can increase the mobility (decrease the restriction) of burn scars. The study will assess the effects of azficel-T (autologous fibroblasts) in subjects who have a unilateral burn scar that is no deeper than the fascia (i.e., underlying structures including ligament, tendon, muscle, and bone must not contribute to the restriction) and that is either:

1. An axillary scar causing 20-60% restriction of shoulder adduction

2. An anterior elbow scar causing 20-60% restriction of elbow extension

3. A dorsal or palmar lesion of a single finger causing 20-60% restriction of flexion or extension

Subjects will each receive 2 injections of azficel-T or placebo administered 14 days (± 7 days) apart (depending on cell availability) and will be followed for efficacy (including range of motion measurements, scar pain and ability to perform activities) to Visit 7 and for safety to Visit 9 at 1 year.

Condition or Disease	Intervention/Treatment	Phase
Restrictive Burn Scars	Biological: Autologous fibroblasts; Biological: placebo sterile saline	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-Blind, Randomized, Placebo-Controlled Pilot Study of Azficel-T for the Treatment of Restrictive Burn Scars
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Autologous fibroblasts Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated.	Biological: Autologous fibroblasts; Other Names: Azficel-T
Placebo Comparator: Sterile saline Sterile saline will be injected into the scar to be evaluated.	Biological: Autologous fibroblasts; Other Names: Azficel-T ; Biological: placebo sterile saline

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline (CFB) of Range of Motion (ROM) of the Affected Joint [Baseline and post-treatment (visit occurred between 194 - 208 days from baseline)]

   Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.

2. Percentage CFB of ROM of the Affected Joint [Baseline and post-treatment (visit occurred between 23 - 37 days from baseline)]

   Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.

3. Percentage CFB of ROM of the Affected Joint [Baseline and post-treatment (visit occurred between 53 - 67 days from baseline)]

   Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.

4. Percentage CFB of ROM of the Affected Joint [Baseline and post-treatment (visit occurred between 93 - 97 days from baseline)]

   Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.

5. Percentage CFB of ROM of the Affected Joint [Baseline and post-treatment (visit occurred between 113 - 127 days from baseline)]

   Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject is at least 18 years of age

2. Subject has a unilateral burn scar of a jointed area (i.e., finger, elbow, shoulder) that is no deeper than the fascia (i.e., underlying structures including ligament, tendon, muscle, and bone must not contribute to the restriction) and that is either:

3. An axillary scar causing 20-60% restriction of shoulder abduction

4. An anterior elbow scar causing 20-60% restriction of elbow extension

5. A dorsal or palmar lesion of a single finger causing 20-60% restriction of flexion or extension

6. Subject's burn scar to be treated is <100 sq cm in size

7. Injury occurred ≤ 36 months prior to screening

8. By the Investigator's assessment, physical therapy will not provide significant continuous improvement to the range of motion of the subject's joint

9. Subject agrees to maintain any current physical therapy regimen for the duration of the study

10. Subject must be able to provide written informed consent and comply with the study requirements

11. Females of childbearing potential must have a negative urine pregnancy test at the screening visit and prior to the first treatment, and must agree to use a reliable means of birth control for the duration of the study

12. Subject has healthy, non-scarred post auricular skin area suitable for biopsy

13. Subject must have a normal complete blood count (CBC) and chemistry panel within 90 days prior to enrollment

Exclusion Criteria:

1. Restrictive burn scars that are primarily classified as keloid scars

2. Subjects for whom a post auricular biopsy cannot be collected for azficel-T production

3. Sunburn or sun damage in the area that will be used for biopsy

4. Plans to initiate any other new scar therapy during the study period

5. Treatment with an investigational product or procedure within 30 days prior to study enrollment or plans to participate in another clinical trial during the course of this study

6. History of active autoimmune disease or organ transplantation

7. Diagnosis of cancer, including basal cell carcinoma, unless successfully treated or in remission for a minimum of 6 months

8. Known genetic disorders affecting fibroblasts or collagen, such as achondroplasia, osteogenesis imperfecta, epidermolysis bullosa, ataxia-telangiectasia, Ehlers Danlos syndrome, etc.

9. Active systemic infection

10. Requires chronic antibiotic or steroidal therapy

11. Any conditions that are considered by the Investigator to be contraindications to biopsy or injection

12. Pregnant or lactating women, or women trying to become pregnant during the study

13. Subject has any disorder that may prevent compliance, such as history of chronic alcohol or drug abuse, significant mental or nervous disorder or other illness that would, in the Investigator's opinion, interfere with the study

14. Presence of other disease or condition that would result in impairment of the range of motion of the extremity, e.g., rheumatoid arthritis or stroke

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of California David Medical Center	Sacramento	California	United States	95817
2	Univ of California San Diego	San Diego	California	United States	92103
3	Division of Burns and Trauma, Jackson Memorial Hospital	Miami	Florida	United States	33136
4	Loyola University Medical Center	Maywood	Illinois	United States	60153
5	Richard M. Fairbanks Burn Center	Indianapolis	Indiana	United States	46202
6	Long Island Plastic Surgical Group	Garden City	New York	United States	11530
7	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
8	Center for Innovation in Restorative Medicine	Pittsburgh	Pennsylvania	United States	15213
9	Univ of Washington, Harborview Medical Center	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Castle Creek Biosciences, LLC.

Investigators

• Principal Investigator: Daniel D Lozano, MD, Lehigh Valley Health Network

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Castle Creek Biosciences, LLC.
• ClinicalTrials.gov Identifier: NCT01858753
• Other Study ID Numbers: FI-B-003
• First Posted: May 21, 2013
• Last Update Posted: Oct 13, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Castle Creek Biosciences, LLC.: burn scars; restrictive; contractures; autologous fibroblasts
• Additional relevant MeSH terms: Cicatrix; Burns

Study Results

Participant Flow

Pre-assignment Detail	Subjects were screened to determine eligibility for the study prior to enrollment. Once the subjects were enrolled, the biopsy was performed within 14 days after screening. Subjects were then randomized sequentially as their cells were harvested and found to be acceptable.

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Period Title: Overall Study
STARTED	5	0
COMPLETED	0	0
NOT COMPLETED	5	0

Baseline Characteristics

Arm/Group Title	Autologous Fibroblasts	Sterile Saline	Total
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline	Total of all reporting groups
Overall Participants	3	0	3
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.0 (13.00)	56.0 (13.00)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN
Male	3 100%	3 Infinity
Region of Enrollment (participants) [Number]
United States	3 100%	3 Infinity
ROM of the Affected Joint (degrees) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees]	124.0 (39.34)	124.0 (39.34)

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline (CFB) of Range of Motion (ROM) of the Affected Joint
Description	Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.
Time Frame	Baseline and post-treatment (visit occurred between 194 - 208 days from baseline)

Outcome Measure Data

Analysis Population Description

Modified intent to treat population (mITT)

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Measure Participants	3	0
Mean (Standard Deviation) [percent change]	52.0 (23.40)

2. Primary Outcome

Title	Percentage CFB of ROM of the Affected Joint
Description	Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.
Time Frame	Baseline and post-treatment (visit occurred between 23 - 37 days from baseline)

Outcome Measure Data

Analysis Population Description

Modified intent to treat population

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Measure Participants	3	0
Mean (Standard Deviation) [percent change]	39.6 (10.88)

3. Primary Outcome

Title	Percentage CFB of ROM of the Affected Joint
Description	Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.
Time Frame	Baseline and post-treatment (visit occurred between 53 - 67 days from baseline)

Outcome Measure Data

Analysis Population Description

Modified intent to treat population

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Measure Participants	3	0
Mean (Standard Deviation) [percent change]	54.9 (25.86)

4. Primary Outcome

Title	Percentage CFB of ROM of the Affected Joint
Description	Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.
Time Frame	Baseline and post-treatment (visit occurred between 93 - 97 days from baseline)

Outcome Measure Data

Analysis Population Description

Modified intent to treat population

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Measure Participants	3	0
Mean (Standard Deviation) [percent change]	56.0 (29.33)

5. Primary Outcome

Title	Percentage CFB of ROM of the Affected Joint
Description	Percentage CFB was calculated by subtracting the baseline ROM measurement from the post-treatment ROM measurement, divided by the baseline ROM measurement, and multiplying by 100.
Time Frame	Baseline and post-treatment (visit occurred between 113 - 127 days from baseline)

Outcome Measure Data

Analysis Population Description

Modified intent to treat population

Arm/Group Title	Autologous Fibroblasts	Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts	Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
Measure Participants	3	0
Mean (Standard Deviation) [percent change]	52.0 (23.40)

Adverse Events

Time Frame	Adverse events were collected from the time of the subject's biopsy through visit 9 (i.e., 360 days from their second treatment).
Arm/Group Title	Autologous Fibroblasts		Sterile Saline
Arm/Group Description	Autologous fibroblasts grown in culture from skin biopsy taken from patient. The cells will be injected into the scars to be treated. Autologous fibroblasts		Sterile saline will be injected into the scar to be evaluated. Autologous fibroblasts placebo sterile saline
All Cause Mortality
	Autologous Fibroblasts		Sterile Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/0 (NaN)
Serious Adverse Events
	Autologous Fibroblasts		Sterile Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Autologous Fibroblasts		Sterile Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/0 (NaN)
General disorders
Injection site pain	1/5 (20%)		0/0 (NaN)
Nervous system disorders
Syncope	1/5 (20%)		0/0 (NaN)

Limitations/Caveats

Early termination leading to small numbers of subjects enrolled and completed; some data uninterpretable due to late data entry. With low enrollment (three subjects in mITT population and five subjects in safety population), a meaningful statistical analysis was not possible for this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.