Phase 3 Study Evaluating Efficacy and Safety of DSC127 Compared With Vehicle and With Standard-of-care in Diabetic Foot Ulcers (STRIDE 2)

A Randomized, Double-Blind, Parallel-group, Vehicle and Standard of Care-controlled Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of DSC127 in Treating Non-healing Foot Ulcers in Subjects With Diabetes Mellitus

To determine if aclerastide (DSC127) is effective in increasing incidence of complete wound closure up to 10 weeks confirmed 2 weeks later, compared with vehicle (gel without active ingredient) and compared with a standard-of-care gel, in subjects with diabetes mellitus (DM) who have chronic Wagner Grade 1 or 2 diabetic foot ulcers, 0.75 - 6cm2 in size.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot Ulcers
• Intervention / Treatment: Drug: placebo vehicle gel; Drug: DSC127; Drug: Standard of Care gel, Aquasite

Detailed Description

Subjects will undergo a two week screening period to assess plantar ulcer healing, and those healing less than 30% will be eligible for randomization providing all other criteria are met. Four weeks of "blinded" randomized treatment follows the screening period, and an observation period of six weeks follows the treatment period. If the ulcer closes during the treatment or observation period, the closure will be confirmed at a visit two weeks later, and at this time the subjects enters a durability assessment period of up to 12 weeks.

All aspects of Standard of Care are followed throughout the study period.

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8R 2R3
      • The Mayer Institute
    • London, Ontario, Canada, N6C 5J1
      • Lawson Health Research Institute
    • Whitby, Ontario, Canada, L1N 2L1
      • Xceed Clinical
  • Quebec
    • Boucherville, Quebec, Canada, J4B 5E4
      • Centre Podiatrique et Soins des Plaies
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre de Recherche du CHUS
• Puerto Rico
  • Aguadilla, Puerto Rico, 00603
    • Centro de Curacion de Heridas del Caribe, Inc.
  • Juana Diaz, Puerto Rico, 00795
    • Office of Renier D. Gonzalez-Cruz, MD
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Wound and Ulcer Care Clinic
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6020
      • GCT - Mercantile Clinical Trial Centre - Primecure Clinic
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Josha Research
    • Bloemfontein, Free State, South Africa, 9301
      • Iatros International
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
      • Worthwhile Clinical Trials
    • Johannesburg, Gauteng, South Africa, 1829
      • Dr Lakha's Consulting Rooms
    • Newtown, Gauteng, South Africa, 2113
      • Newtown Clincal Research Centre
    • Sunninghill, Gauteng, South Africa, 2157
      • Sunninghill Hospital
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4001
      • Synapta Clinical Research Centre
    • Durban, KwaZulu Natal, South Africa, 4092
      • Flamco Clinical Trials
    • Phoenix, KwaZulu Natal, South Africa, 4068
      • Brookedale Clinical Research Centre
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • Tiervlei Trial Centre, Karl Bremer Hospital
    • Parow, Western Cape, South Africa, 7505
      • TREAD Research
    • Worcester, Western Cape, South Africa, 6850
      • Boland Ethical Research Group
  • ZwaZulu Natal
    • Durban, ZwaZulu Natal, South Africa, 4091
      • Randles Road Medical Centre
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • East Valley Foot and Ankle Specialist
    • Phoenix, Arizona, United States, 85032
      • Precision Trials
    • Phoenix, Arizona, United States, 85015
      • Associated Foot & Ankle Specialists, PC
    • Phoenix, Arizona, United States, 85032
      • Ledesma Foot and Ankle
    • Phoenix, Arizona, United States, 85008
      • Arizona Burn Center Maricopa Medical Center
  • California
    • Castro Valley, California, United States, 94546
      • Center for Clinical Research, Inc.
    • Chino, California, United States, 91710
      • Reliance Institute of Clinical Research
    • Encino, California, United States, 91316
      • Vladimir Zeetser, DPM
    • Los Angeles, California, United States, 90063
      • Innovative Medical Technologies, LLC
    • Oakland, California, United States, 94609
      • Samuel Merritt University, California School of Podiatric Medicine
    • San Francisco, California, United States, 94115
      • Center for Clinical Research, Inc.
  • Colorado
    • Denver, Colorado, United States, 80220
      • The Diabetic Foot and Wound Center
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Orthopedic Research Associates
    • Fort Lauderdale, Florida, United States, 33308
      • InvesClinic, LLC
    • Hialeah, Florida, United States, 33013
      • Research In Miami, Inc.
    • Jacksonville, Florida, United States, 32207
      • River City Clinical Research
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33165
      • Phoenix Medical Research
    • Miami, Florida, United States, 33136
      • Advanced Pharma CR, LLC
    • Miami Beach, Florida, United States, 33140
      • New Phase Clincal Trials, Inc.
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Bluegrass Foot Center c/o Research Concierge, LLC
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Grace Research
  • Michigan
    • Southfield, Michigan, United States, 48034
      • American Center for Clinical Trials
  • New Jersey
    • Emerson, New Jersey, United States, 07630
      • Dr. Vincent Giacalone
  • North Carolina
    • Goldsboro, North Carolina, United States, 27533
      • Wayne Memorial Hospital
    • Wilmington, North Carolina, United States, 24801
      • O'Malley Foot and Ankle
  • Ohio
    • Lima, Ohio, United States, 45801
      • Regional Infectious Disease & Infusion Center Inc.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Clinic
    • York, Pennsylvania, United States, 17403
      • Martin Foot & Ankle
  • Texas
    • Dallas, Texas, United States, 75231
      • North Texas Podiatric Medicine & Surgery
    • Fort Worth, Texas, United States, 76104
      • Bone and Joint Institute
    • Houston, Texas, United States, 77074
      • Houston Foot & Ankle Specialists
  • Utah
    • Salt Lake City, Utah, United States, 84119
      • Redwood Health Center

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:

• Male or female ambulatory subject age ≥18 years at the time of informed consent
• Has type 1 or type 2 DM under metabolic control as confirmed by a glycosylated hemoglobin (HbA1c) of ≤12% and a serum creatinine level of ≤3mg/dL

• At Screening and Baseline (prior to randomization), subject has at least one ulcer that fulfills all of the following criteria:

  • present for ≥1 month and ≤1 year
  • Partial- or full- thickness and not involving bone, tendon, or capsule (probing to tendon or capsule), i.e. Wagner Grade 1 or 2.
  • Has no sign of infection or osteomyelitis
  • Plantar neuropathic ulcer - predominately be on the plantar surface (i.e. weight bearing) of the foot to ensure adequate off-loading and may include the toes
  • Size of the target ulcer must be 0.75-6 cm2.

  • Target ulcer must be non-healing as defined as <30% reduction in area in response to standard of care during the Screening Period

    • If more than one ulcer is present that meets the inclusion criteria, the largest one will be considered the target ulcer
    • If there are two ulcers of the same size that meet all criteria, the one with the higher Wagner Grade will be considered the target ulcer
    • If there are two ulcers of the same size and the same Wagner Grade, the one present for the longest qualifying time will be the target ulcer.
    • Non-target ulcers will also be treated according to standard of care (Acute Charcot Neuroarthropathy of the foot with the target ulcer must be excluded)
• Has an ankle brachial index (ABI) ≥0.7 on the foot with the target ulcer.
• Has an assessment of the baseline level of neuropathy of the foot using Semmes-Weinstein filaments.
• A female subject of childbearing potential must have a negative serum pregnancy test at the time of Screening.
• A female subject of childbearing potential must be willing to use a medically acceptable method of birth control, such as Essure®, hormonal contraception (oral pills, implantable device, or skin patch), intrauterine device, tubal ligation, or double barrier throughout the study. A female subject of childbearing potential who practices abstinence is not required to employ birth control.
• Has the ability and willingness to understand and comply with study procedures and to give written informed consent prior to enrollment in the study or initiation of study procedures

Exclusion Criteria:

• Has a known hypersensitivity to any of the investigational drug or vehicle or standard of care gel components
• Has been exposed to any investigational agent within 30 days of entry into the study
• A female who is pregnant or nursing
• Has active malignant disease of any kind except for basal cell carcinoma (of the skin). A subject, who has had a malignant disease in the past, was treated and is currently disease-free, may be considered for study entry.
• Has a hemoglobin of less than 8.5 gm/dL.
• Transaminase levels greater than 3 × normal
• Is receiving hemodialysis or chronic ambulatory peritoneal dialysis (CAPD) therapy
• Has had prior radiation therapy to any part of the foot with the target ulcer under study
• Use of systemic corticosteroids and immunosuppressants (within the 8 weeks prior to screening)
• Has an ulcer primarily ischemic in etiology
• Has sickle-cell anemia, Reynaud's, or peripheral vascular disease
• Has received a biologic agent, growth factor, or skin equivalents (Regranex®, Apligraft, or Dermagraft), in the past 30 days
• Has a target ulcer which is determined to be clinically infected and requires antimicrobials. Any antibiotic therapy must be completed or discontinued at Screening.
• Has a Wagner Grade 3 or higher DFU, deep abscess, or gangrene
• Has uncontrolled hypertension, in the opinion of the Investigator.
• Any other finding, which in the opinion of the Investigator, may interfere with the assessment of the product or participation of the patient in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DSC127; DSC127 0.03% in a vehicle gel (hydroxyethyl cellulose (HEC) with parabens)	Drug: DSC127; DSC127 0.03%, daily topical application to diabetic foot ulcer for a period of up to 28 days or until ulcer closure, whichever occurs sooner.
Placebo Comparator: Vehicle gel; Vehicle gel comprising HEC with parabens	Drug: placebo vehicle gel
Placebo Comparator: Standard of Care gel; Aquasite gel, as standard of care gel	Drug: Standard of Care gel, Aquasite

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with a target ulcer which achieves complete wound closure by 10 weeks (confirmed 2 weeks later) after initiation of treatment.	Primary endpoint of complete closure is assessed by the Principal Investigator at the site; ulcer measurements are calculated via tracings submitted to the Canfield system, and photographs are collected as confirmation of closure via the Canfield system. Assessment of aclerastide (DSC127) vs vehicle control.	Target ulcer must achieve complete wound closure by 10 weeks post first treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with a target ulcer which achieves complete wound closure by 10 weeks (confirmed two weeks later) after initiation of treatment.	Primary endpoint of complete closure is assessed by the Principle Investigator at the site; ulcer measurements are calculated via tracings submitted to the Canfield system, and photographs are collected as confirmation of closure via the Canfield system. Assessment of aclerastide (DSC127) vs Standard of Care control.	Target ulcer must achieve complete wound closure by 10 weeks post first treatment

Other Outcome Measures

Outcome Measure	Time Frame
Time to the visit where the target ulcer achieves confirmed complete wound closure	Measurements to ten weeks post first dose
Percent reduction in target ulcer area per week.	Up to ten weeks post first dose
Incidence of and time to target ulcer recurrence after confirmed complete wound closure has been established.	To a maximum of 24 weeks post first dose

Collaborators and Investigators

• Sponsor: Integra LifeSciences Corporation
• Collaborators: Integrium
• Investigators: Study Director: Alan Dunton, MD, Integra LifeSciences Corporation

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 8, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 8, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: diabetic foot ulcers; Wagner Grade 1 or 2 ulcers
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: DSC127-2012-02