Clinical trial NCT03028415: AMPLEX Ankle Fusion and Hindfoot
Official title: A Multi-Center, Randomized, Pivotal Study Evaluating AMPLEX Compared To Autogenous Bone Graft in Subjects Indicated for Arthrodesis Surgery Involving the Hindfoot or Ankle
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Arthrodesis Surgery Involving the Hindfoot or Ankle
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-01-23
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To demonstrate that AMPLEX is non-inferior to autogenous bone graft (ABG) for bone fusion in a population indicated for single, double, or triple hindfoot arthrodesis or ankle arthrodesis surgery with supplemental graft material.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Indicated for ankle or hindfoot arthrodesis and require one of the following arthrodesis procedures:

Tibiotalar (ankle); Talocalcaneal (subtalar); Talonavicular; Calcaneocuboid; Double hindfoot (e.g., talonavicular and talocalcaneal joints); Triple hindfoot (subtalar, talonavicular and calcaneocuboid joints)

* Presents with pain on weight-bearing of at least 40 mm on a 100 mm VAS at the area indicated for arthrodesis
* Presents with at least one comorbid risk factors that warrant the use of supplemental autogenous bone or allograft:

Radiographic evidence of bone defect, deficit, subsidence or subchondral cyst; More than one joint to be fused; Involvement of other adjacent or nonadjacent joints; Large surface area; Intra-articular or extra-articular deformity; Post-traumatic arthritis; Diagnosis of osteoporosis

* The Investigator determines if the joint space(s) can be adequately filled with graft material (AMPLEX or ABG) according to the following parameters:

Single hindfoot joint fusion: up to 5 cm\^3; Double or triple hindfoot fusion: each individual joint up to 5 cm\^3, but overall, not more than 10 cm3 for the full complement of joints; Ankle fusion: up to 10 cm\^3

* Each fused joint can be rigidly stabilized with with at least 1 and no more than 3 screws across the fusion plane. (Supplemental pins and staples may be used, as well as supplemental screws and plates external to the fusion site(s))
* Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations
* For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and within 24 hours prior to procedure. These trial participants must commit to adequate birth control (e.g., oral contraceptive, two methods of barrier birth control, or abstinence) through the 78 week follow-up

Exclusion Criteria:

* Bone deficit requiring a structural graft
* Charcot foot disease
* Radiographic evidence of open physes
* Prior arthroplasty, arthrodesis, major surgical repair or reconstruction of the index ankle or hindfoot joint(s)
* Requires osteotomy or fusion of the midfoot joints
* BMI greater than 45 kg/m\^2
* Documented medical history of, or radiographic evidence of, a bone disease (e.g. avascular necrosis) or other condition (e.g., osteolysis) that would preclude the subject from receiving screw fixation in the opinion of the surgeon
* Requires intramedullary nail fixation or an external fixator
* Comorbidity that would limit the ability to administer any functional measurements such as FAAM-ADL
* Has at the time of surgery, a systemic infection or local infection at the site of surgery
* Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease)
* HgbA1c level greater than or equal to 8%
* Known hypersensitivity to any of the components of the product \[e.g. B2A peptide, Hydroxyapatite (HA): beta-tricalcium phosphate (βTCP), ceramic granule\]
* Currently receiving treatment with a drug known to interfere with bone metabolism \[e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate\]
* Has previously received treatment with a drug known to interfere with bone metabolism \[e.g., systemic corticosteroid therapy (topical corticosteroid therapy is permissible), methotrexate\] and in the opinion of the investigator could continue to negatively interfere with bone metabolism or bone healing
* History of any severe allergy or anaphylaxis, or a history of hypersensitivity to protein pharmaceuticals \[e.g., monoclonal antibodies or gamma globulins, recombinant Bone Morphogenetic Proteins (BMPs)\]
* Medical condition requiring radiation, chemotherapy or immunosuppression
* Have a prior or active history of malignancy (except for basal cell carcinoma of the skin)
* Has a history of autoimmune disease known to affect bone metabolism. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, Grave's disease and Hashimoto's thyroiditis; Rheumatoid Arthritis is allowed
* Have pathological or genetic liver disease or who have clinically significant, elevated baseline liver function enzymes
* Has obvious and/or documented alcohol or illicit drug addictions
* Is a prisoner in a correctional institution/facility
* Actively involved in litigation or workman's compensation
* Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization
* Requires chronic therapeutic use of NSAID during the first 6 post-operative weeks (except aspirin up to 325 mg bid for cardiovascular protection and/or DVT prophylaxis)
* Has previously been treated with, or exposed to, therapeutic levels of synthetic or recombinant BMPs
* Requires chronic subcutaneous or intravenous heparin therapies

Primary outcomes:
measure: Proportion of Subjects Who Met All Five Criteria for Subject Performance Composite (SPC) Endpoint
timeFrame: At week 52
Secondary outcomes:
measure: Proportion of Subjects Achieving Computerized Tomography (CT) Radiographic Fusion Success
timeFrame: At week 52
measure: Proportion of Subjects Achieving CT Radiographic Fusion Success
timeFrame: At week 12
measure: Proportion of Subjects Achieving CT Radiographic Fusion Success
timeFrame: At week 24
measure: Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
timeFrame: Baseline, and at week 12
measure: Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
timeFrame: Baseline, and at week 24
measure: Proportion of Subjects With Change From Baseline in Pain on Weight-bearing at Fusion Site (>20 mm Reduction From Baseline on 100 mm VAS)
timeFrame: Baseline, and at week 52
measure: Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
timeFrame: At week 2
measure: Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
timeFrame: At week 6
measure: Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
timeFrame: At week 12
measure: Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
timeFrame: At week 24
measure: Proportion of Subjects With Absence of Graft Harvest Site Pain (<20 mm on 100 mm VAS)
timeFrame: At week 52
measure: Change From Baseline in FAAM-ADL
timeFrame: Baseline, and at week 12
measure: Change From Baseline in FAAM-ADL
timeFrame: Baseline, and at week 24
measure: Change From Baseline in FAAM-ADL
timeFrame: Baseline, and at week 52
measure: Subject Performance Composite (SPC) Endpoint
timeFrame: At week 12
measure: Subject Performance Composite (SPC) Endpoint
timeFrame: At week 24
measure: Change From Baseline in Short Form-12 (SF-12)
timeFrame: Baseline, and at week 24
measure: Change From Baseline in Short Form-12 (SF-12)
timeFrame: Baseline, and at week 52
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Physician Research Group
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: San Francisco
country: United States
facility: California Pacific Orthopaedics
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Gulf Breeze
country: United States
facility: Andrews Orthopaedic and Sports Medicine Center
state: Florida
city: Atlanta
country: United States
facility: Emory Orthopaedic and Spine Hospital
state: Georgia
city: Chicago
country: United States
facility: Midwest Orthopedics at Rush
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore, Inc / Rubin Institute for Advanced Orthopedics
state: Maryland
city: Baltimore
country: United States
facility: Medstar
state: Maryland
city: Grand Rapids
country: United States
facility: Orthopaedic Associates of Michigan, Research and Education Institute
state: Michigan
city: Lansing
country: United States
facility: Michigan Orthopedic Center
state: Michigan
city: Bloomington
country: United States
facility: TRIA Orthopaedic Center
state: Minnesota
city: Las Vegas
country: United States
facility: Desert Orthopaedic Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Newark
country: United States
facility: Rutgers
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: OrthoCarolina Research Institute, Inc.
state: North Carolina
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Reconstructive Orthopaedic Associates
state: Pennsylvania
city: State College
country: United States
facility: University Orthopedics Center
state: Pennsylvania
city: Germantown
country: United States
facility: Campbell Clinic Orthopaedics
state: Tennessee
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Baylor St. Luke's Medical Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Edmonton
country: Canada
facility: University of Alberta System
state: Alberta
city: Red Deer
country: Canada
facility: Central Alberta Orthopedics
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: University of Laval
state: Quebec
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: