Safety and Feasibility of ADRCs Treatment To Patients With Thermal Wounds

Safety and Feasibility of Adipose Derived Regenerative Cells (ADRCs) in the Treatment of Deep Partial Thickness and Full Thickness Thermal Wounds (RELIEF)

The primary objective of the protocol is to evaluate preliminary safety and feasibility of ADRCs via intravenous delivery in the treatment of deep partial and full thickness thermal wounds.

Study Overview

• Status: Suspended
• Conditions: Thermal Burn
• Intervention / Treatment: Device: Device-ADRCs intravenously infusion

Detailed Description

The RELIEF Trial is a prospective, open-label, parallel group, usual care controlled, multi-center randomized (2:1, active: usual care alone) safety and feasibility study targeting thermal burns. Subjects will have at least one deep partial or full thickness burn wounds of > 250 cm2 that is to be autografted with a split thickness meshed skin graft (STSG). Subjects randomized to ADRCs will undergo small volume fat harvest (100 to 150 mL) performed at initiation of general anesthesia for scheduled burn surgery followed by intravenous delivery of ADRCs within 4 hours following surgery. The lipoaspirate will be processed in the Celution® System to isolate and concentrate ADRCs.

Following informed consent and initial screening assessments, eligible subjects will undergo pre-operative testing. On the procedure day, subjects will be randomized to ADRCs (with usual care) or usual care alone. Low volume lipoharvest will only be performed on subjects randomized to ADRCs in order to obtain 100-150 mL lipoaspirate, which will then be transferred to the Celution® System for processing to isolate and concentrate ADRCs for same-day administration. All treatment will be delivered in a total volume of 10 mL which will be delivered by slow intravenous administration into a peripheral vein.

Following surgery, subjects will be evaluated at first dressing change, day 10 (±2) (only if wound dressing change planned) and weeks 2 (±3 days), 3 (±3 days), 4 (±3 days), 8 (±7 days), 12 (±14 days), 26 (±14 days), and 52(±21 days).

The 1st 5 subjects enrolled in active treatment will be observed for adverse events over a 7 day period. If no SAEs occur during that period, for that individual subject, the next subject enrolled in active treatment may be entered with the same 7 day observation period. The safety results of the first 5 subjects will be reviewed by the DMC and their evaluation will be used in conjunction with the clinical data collected to date, and if appropriate, to potentially remove the staggering approach to the study. Enrollment after the first 5 subjects may continue only after the DMC has completed its safety review and recommends continuation.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Maricopa IHS
  • California
    • Los Angeles, California, United States, 90033
      • Univeristy of Southern California
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females age ≥ 18 to ≤ 65
• BMI > 20 kg/m2
• Burn TBSA 20% - 50%
• At least one deep partial thickness and/or full thickness thermal burn ≥ 250 cm2 on the arms, legs, back, abdomen or chest that is anticipated to be covered with autologous meshed STSG meshed and that has not been treated previously with a biologic dressing such as Alloderm® or Integra®
• Ability to safely undergo tissue harvest that is anticipated to yield >150mL of adipose tissue at a site that is free from infection
• Donor site availability for skin graft harvest
• Able to provide written informed consent signed by either the patient or their legally authorized representative
• Women and men of child-bearing potential agreeing to use contraception during the study. Acceptable methods include surgical sterility, IUDs, hormonal contraception or double barrier methods

Exclusion Criteria:

• Subjects with burns > 3rd degree (i.e. involvement of deeper tissues, such as muscle, tendons, or bone)
• Subjects with electrical or chemical burns
• Subjects with significant inhalation injuries necessitating intubation and mechanical ventilation or requiring > 50% FI02 on a continuous basis to maintain oxygenation (02 sat > 90%)
• In the opinion of treating physician, patient not expected to survive beyond 30 days
• Pre-existing condition requiring current use of immunosuppressive medication or systemic steroids
• Pregnant or lactating status. Pregnancy as determined by a positive pregnancy test at screening or baseline
• Known history of HIV infection, or active Hepatitis B or active Hepatitis C infection
• Cancer requiring chemotherapy or radiation within previous 6 months or resection within the last 5 years (other than basal cell carcinoma)
• Known chronic renal failure (serum creatinine > 2 mg/dL) or chronic liver disease
• Pre-existing medical conditions that would interfere with wound healing (i.e.diabetic patients with Hemoglobin A1c test result ≥8%, malignancy, autoimmune disease)
• Subjects with psychiatric conditions that are anticipated to result in protocol noncompliance
• Chronic illicit drug or alcohol abuse that is anticipated to interfere with patient compliance with the protocol
• Participation in another clinical trial within 60 days of the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Group; Device-ADRCs intravenously infusion 20 million ADRCs generated by Celution device will be intraveously infused through peripheral vein. Standard care of split thickness meshed skin graft (STSG) will be used.	Device: Device-ADRCs intravenously infusion; Medical Device: ADRCs Generated by Celution 800 IV Device and then Infused into Peripheral Vein.
NO_INTERVENTION: Usual Care; Standard care of split thickness meshed skin graft (STSG) will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of obtain lipo suction with > 100mL adipose tissue, Feasibility if obtain 20 million ADRC	Feasibility will be determined as 1) the ability to obtain > 100 mL adipose tissue during the liposuction surgical procedure (up to one hour for the tissue harvesting procedure), 2) obtain ≥ 20 x 106 ADRCs confirmed by cell counting (up to 4 hours after the liposuction procedure), and 3) deliver the prepared cell dose to the subject within four hours after Celution device completed the process.	Procedure day only
Incidence of Treatment-Emergent Adverse Events [Safety]	Safety will be evaluated based on the incidence, type and seriousness of adverse events related to the IV administration of test substance as well as the low volume lipoharvest procedure. Adverse events will be assessed according to the NIH Common Terminology Criteria for Adverse Events (CTCAE) v4.0 for scale grading adverse events.	Throughout the whole 52 weeks trial evaluation period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent epithelialization of the graft	Percent epithelialization of the graft post grafting (assessed by surgeon visual evaluation and blinded independent review of standardized photographs)	At first dressing change, day 10 and weeks 2, 3 and 4.
Percent take of the graft	Percent take of the graft post grafting (assessed by surgeon visual evaluation and blinded independent review of standardized photographs)	At first dressing change, day 10 and weeks 2, 3 and 4.
Percent of wound with complete closure	Percent of wound closure post grafting (assessed by surgeon visual evaluation and blinded independent review of standardized photographs)	At weeks 2, 3, 4, 8 and 12

Collaborators and Investigators

• Sponsor: Cytori Therapeutics
• Investigators: Principal Investigator: Marc H Hedrick, MD, Cytori therapeutics Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2018
• Primary Completion (ANTICIPATED): July 31, 2020
• Study Completion (ANTICIPATED): July 31, 2021

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (ACTUAL): February 15, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Skin Graft; Thermal Burn; Adipose Derived Regenerative Cells
• Other Study ID Numbers: RELIEF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes