Clinical trial NCT01849965: Phase 3 Study Evaluating Efficacy and Safety of DSC127 Compared With Vehicle and With Standard-of-care in Diabetic Foot Ulcers
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Diabetic Foot Ulcers
Keywords: diabetic foot ulcers
Wagner Grade 1 or 2 ulcers
Lead sponsor: Integra LifeSciences Corporation
Sponsor class: INDUSTRY
Collaborators: name: Integrium
First posted: 2013-05-09
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of subjects with a target ulcer which achieves complete wound closure by 10 weeks (confirmed 2 weeks later) after initiation of treatment.
timeFrame: Target ulcer must achieve complete wound closure by 10 weeks post first treatment
Secondary outcomes:
measure: The proportion of subjects with a target ulcer which achieves complete wound closure by 10 weeks (confirmed two weeks later) after initiation of treatment.
timeFrame: Target ulcer must achieve complete wound closure by 10 weeks post first treatment
Other outcomes:
measure: Time to the visit where the target ulcer achieves confirmed complete wound closure
timeFrame: Measurements to ten weeks post first dose
measure: Percent reduction in target ulcer area per week.
timeFrame: Up to ten weeks post first dose
measure: Incidence of and time to target ulcer recurrence after confirmed complete wound closure has been established.
timeFrame: To a maximum of 24 weeks post first dose
Locations:
city: Mesa
country: United States
facility: East Valley Foot and Ankle Specialist
state: Arizona
city: Phoenix
country: United States
facility: Arizona Burn Center Maricopa Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Associated Foot & Ankle Specialists, PC
state: Arizona
city: Phoenix
country: United States
facility: Ledesma Foot and Ankle
state: Arizona
city: Phoenix
country: United States
facility: Precision Trials
state: Arizona
city: Castro Valley
country: United States
facility: Center for Clinical Research, Inc.
state: California
city: Chino
country: United States
facility: Reliance Institute of Clinical Research
state: California
city: Encino
country: United States
facility: Vladimir Zeetser, DPM
state: California
city: Los Angeles
country: United States
facility: Innovative Medical Technologies, LLC
state: California
city: Oakland
country: United States
facility: Samuel Merritt University, California School of Podiatric Medicine
state: California
city: San Francisco
country: United States
facility: Center for Clinical Research, Inc.
state: California
city: Denver
country: United States
facility: The Diabetic Foot and Wound Center
state: Colorado
city: Boynton Beach
country: United States
facility: Orthopedic Research Associates
state: Florida
city: Fort Lauderdale
country: United States
facility: Invesclinic, LLC
state: Florida
city: Hialeah
country: United States
facility: Research in Miami, Inc.
state: Florida
city: Jacksonville
country: United States
facility: River City Clinical Research
state: Florida
city: Miami Beach
country: United States
facility: New Phase Clincal Trials, Inc.
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Phoenix Medical Research
state: Florida
city: Owensboro
country: United States
facility: Bluegrass Foot Center c/o Research Concierge, LLC
state: Kentucky
city: Shreveport
country: United States
facility: Grace Research
state: Louisiana
city: Southfield
country: United States
facility: American Center for Clinical Trials
state: Michigan
city: Emerson
country: United States
facility: Dr. Vincent Giacalone
state: New Jersey
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Wilmington
country: United States
facility: O'Malley Foot and Ankle
state: North Carolina
city: Lima
country: United States
facility: Regional Infectious Disease & Infusion Center Inc.
state: Ohio
city: Philadelphia
country: United States
facility: Paddington Testing Clinic
state: Pennsylvania
city: York
country: United States
facility: Martin Foot & Ankle
state: Pennsylvania
city: Dallas
country: United States
facility: North Texas Podiatric Medicine & Surgery
state: Texas
city: Fort Worth
country: United States
facility: Bone and Joint Institute
state: Texas
city: Houston
country: United States
facility: Houston Foot & Ankle Specialists
state: Texas
city: Salt Lake City
country: United States
facility: Redwood Health Center
state: Utah
city: Hamilton
country: Canada
facility: The Mayer Institute
state: Ontario
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Whitby
country: Canada
facility: Xceed Clinical
state: Ontario
city: Boucherville
country: Canada
facility: Centre Podiatrique et Soins des Plaies
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de recherche du CHUS
state: Quebec
city: Aguadilla
country: Puerto Rico
facility: Centro de Curacion de Heridas del Caribe, Inc.
city: Juana Diaz
country: Puerto Rico
facility: Office of Renier D. Gonzalez-Cruz, MD
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: Wound and Ulcer Care Clinic
city: Port Elizabeth
country: South Africa
facility: GCT - Mercantile Clinical Trial Centre - Primecure Clinic
state: Eastern Cape
city: Bloemfontein
country: South Africa
facility: Iatros International
state: Free State
city: Bloemfontein
country: South Africa
facility: Josha Research
state: Free State
city: Benoni
country: South Africa
facility: Worthwhile Clinical Trials
state: Gauteng
city: Johannesburg
country: South Africa
facility: Dr Lakha's Consulting Rooms
state: Gauteng
city: Newtown
country: South Africa
facility: Newtown Clincal Research Centre
state: Gauteng
city: Sunninghill
country: South Africa
facility: Sunninghill Hospital
state: Gauteng
city: Durban
country: South Africa
facility: Synapta Clinical Research Centre
state: KwaZulu Natal
city: Durban
country: South Africa
facility: Flamco Clinical Trials
state: KwaZulu Natal
city: Phoenix
country: South Africa
facility: Brookedale Clinical Research Centre
state: KwaZulu Natal
city: Cape Town
country: South Africa
facility: Tiervlei Trial Centre, Karl Bremer Hospital
state: Western Cape
city: Parow
country: South Africa
facility: Tread Research
state: Western Cape
city: Worcester
country: South Africa
facility: Boland Ethical Research Group
state: Western Cape
city: Durban
country: South Africa
facility: Randles Road Medical Centre
state: ZwaZulu Natal
Study officials:
affiliation: Integra LifeSciences Corporation
name: Alan Dunton, MD
role: STUDY_DIRECTOR
References: