Dose Finding Study of HP802-247 in Venous Leg Ulcers

A Phase II Randomized, Double Blind, Placebo Controlled Dose Finding Study Investigating the Efficacy of HP802-247 in Venous Leg Ulcers

This is a 16-week study for subjects with a venous leg ulcer between the knee and ankle. This research is being done to determine the effectiveness of two dosing frequencies and two different concentrations of HP802-247, together with standard care, compared to placebo, plus standard care.

Study Overview

• Status: Completed
• Conditions: Venous Leg Ulcer; Venous Stasis Ulcers
• Intervention / Treatment: Biological: HP802-247; Biological: Placebo (Vehicle)

• Study Type: Interventional
• Enrollment (Actual): 228
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6C5J1
      • Aging Rehabilitation & Geriatric Care Research Center
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of AZ College of Medicine
  • California
    • Castro Valley, California, United States, 94546
      • Center for Clinical Research
    • Encinitas, California, United States, 92024
      • ILD Consulting, Inc.
    • Los Angeles, California, United States, 90048
      • Vascular Surgery Associates
    • San Diego, California, United States, 92013
      • UCSD Wound Treatment and Research Center
  • Florida
    • Miami, Florida, United States, 33186
      • University of Miami
    • South Miami, Florida, United States, 33143
      • Doctors Research Network
    • Tamarac, Florida, United States, 33321
      • Robert J. Snyder
  • Illinois
    • Chicago, Illinois, United States, 60154
      • Northwestern University Feinberg School of Medicine
    • Jacksonville, Illinois, United States, 62650
      • Passavant Area Hospital
    • North Chicago, Illinois, United States, 60064
      • Rosalind Franklin University
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Wound Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Stoughton, Massachusetts, United States, 02972
      • New England Sinai Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Advanced Foot and Ankle Center
  • New Jersey
    • Emerson, New Jersey, United States, 07630
      • Vincent Giacalone
    • New York, New Jersey, United States, 10025
      • St. Luke's Roosevelt Hospital Center
    • Summit, New Jersey, United States, 07901
      • Overlook Hospital Wound Healing Program
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17112
      • Harrisburg Foot and Ankle Center
    • Reading, Pennsylvania, United States, 19601
      • Center for Advanced Wound Care
  • Texas
    • Arlington, Texas, United States, 76011
      • Arlington Research Center
    • Dallas, Texas, United States, 75093
      • Wound Care Consultants
    • Lubbock, Texas, United States, 79410
      • Southwest Regional Wound Care Center
    • San Antonio, Texas, United States, 78205
      • Peripheral Vascular Associates
  • Utah
    • St. George, Utah, United States, 84770
      • Dixie Regional Medical Center's Wound Clinic
  • Washington
    • Bellevue, Washington, United States, 98004
      • Lake Washington Vascular, LLC
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center Wound Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide informed consent.
• Willing to comply with protocol instructions, including allowing all study assessments.
• Have a venous leg ulcer (venous etiology)between the knee and ankle, at or above the malleolus.
• Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
• Target ulcer duration greater than or equal to 6 weeks but less than or equal to 24 months.

Exclusion Criteria:

• Women who are pregnant or lactating
• Therapy with another investigational agent within thirty (30) days of Screening, or during the study.
• A target ulcer of non-venous etiologies.
• Refusal of or inability to tolerate compression therapy.
• Therapy of the target ulcer with tissue-engineered cell-based skin equivalents within 30 days preceding the Screening Visit.
• Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A - Low Q7D; Low dose HP802-247, applied at each visit	Biological: HP802-247; One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.
Experimental: B - Low Q14D; Low dose HP802-247 applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12	Biological: HP802-247; One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.
Experimental: C - High Q7D; High dose HP802-247, applied at each visit	Biological: HP802-247; One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.
Experimental: D - High Q14D; High dose HP802-247, applied at Visits 1, 3, 5, 7, 9, 11 and Placebo at Visits 2, 4, 6, 8, 10, and 12	Biological: HP802-247; One dose of HP802-247 consists of 260 microliters (uL) containing keratinocytes and fibroblasts totaling 0.5 x 10-6 power or 5.0 x 10-6 power cells per mL, plus fibrin.
Placebo Comparator: E - Vehicle; Placebo (Vehicle), applied at each visit	Biological: Placebo (Vehicle); Placebo (Vehicle) consisting of: Component 1 - acellular fibrinogen solution; Component 2 - acellular thrombin solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Average Percent (%) Change From Baseline in the Target Wound Area in Each Treatment Group Over the Twelve-week Double-blind Treatment Period.	For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, or until wound closure, whichever occurred first, using a laser-based wound imaging system in conjunction with software to measure area. An average of the 12 measurements were assessed.	Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Probability of Non-Closure	This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis.	14 weeks - the final visit for one subject was delayed by two weeks
Percent of Change From Baseline in Target Wound Area at Each of the Twelve Double-blind Treatment Weeks.	For each treatment group the area of each subject's target ulcer was measured on a weekly basis, for up to 12 weeks, using a laser-based wound imaging system in conjunction with software to measure area.	Weekly, over the 12 week treatment period, or until wound closure, which ever occurred first
Proportion of Subjects Achieving ≥ 50% Decrease in Target Wound Area From Baseline Through Week 13	The area of each subject's target wound was measured at each visit and the proportion of subjects with a decrease in area from baseline ≥ 50% was calculated for each treatment group.	Over the 12 week treatment period or until the wound closed, which ever occurred first.
Percentage of Participants With Complete Wound Closure at Each Visit	Treatment groups were compared for the proportion of wounds closed at each weekly visit. For subjects who dropped from the study, their remaining visit values were imputed using LOCF.	Weekly, over the 12 week treatment period
Target Ulcer Pain Was Measured Using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects Marked Their Pain Level on a 100 mm Horizontal Line, With a Short Vertical Line Across the Scale, 0 Denoting no Pain and 100mm the Maximum Pain.	Target ulcer pain was measured using a Visual Analog Scale [Range: 0mm - 100mm]. Subjects marked their pain level on a 100 mm horizontal line, with a short vertical line across the scale, 0 denoting no pain and 100mm the maximum pain. Each weekly measurement is reported as the average of all subjects scores at each week per treatment group.	Weekly, over the 12 week treatment period
Median Time to Achieve Complete Wound Closure, Based on Based on a Kaplan-Meier Survival Analysis, Over the 12-Week Treatment Period From Baseline.	This key secondary outcome was the days to wound closure based on a Kaplan-Meier survival analysis.	14 weeks - the final visit for one subject was delayed by two weeks

Collaborators and Investigators

• Sponsor: Healthpoint
• Investigators: Principal Investigator: William Marston, MD, University of North Carolina; Principal Investigator: Robert Kirsner, MD, University of Miami; Principal Investigator: Robert J Snyder, MD, Robert J Snyder

Publications and helpful links

General Publications

• Kirsner RS, Marston WA, Snyder RJ, Lee TD, Cargill DI, Slade HB. Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2012 Sep 15;380(9846):977-85. doi: 10.1016/S0140-6736(12)60644-8. Epub 2012 Aug 3.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 26, 2009
• First Posted (Estimate): February 27, 2009

Study Record Updates

• Last Update Posted (Estimate): October 24, 2016
• Last Update Submitted That Met QC Criteria: September 13, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Leg Ulcer; VLU; Leg Wound; Venous Leg Ulcer (VLU); Venous Stasis Ulcer (VSU); VSU
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: 802-247-09-015