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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02718131




Registration number
NCT02718131
Ethics application status
Date submitted
7/03/2016
Date registered
24/03/2016

Titles & IDs
Public title
A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)
Scientific title
A Study of INFUSE Bone Graft (Recombinant Human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis 1 (NF1)
Secondary ID [1] 0 0
W81XWH-12-1-0155
Secondary ID [2] 0 0
NF107
Universal Trial Number (UTN)
Trial acronym
NF107-BMP2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
NF1 0 0
Congenital Pseudarthrosis of Tibia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Skin 0 0 0 0
Dermatological conditions
Cancer 0 0 0 0
Other cancer types
Injuries and Accidents 0 0 0 0
Fractures
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - INFUSE Bone Graft (BMP-2)
Treatment: Surgery - Control Group

Active comparator: INFUSE Bone Graft (BMP-2) - Children with NF1 and tibial pseudarthrosis who require surgery will have the INFUSE bone graft added to their surgical protocol. After a standard surgical approach of resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest; in addition, the INFUSE bone graft in the form of a collagen sponge will be wrapped around the tibia during the surgical process.

Placebo comparator: Control Group - Children with NF1 and tibial pseudarthrosis who require surgery will receive the standard surgical protocol only. This includes resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest.


Treatment: Devices: INFUSE Bone Graft (BMP-2)
The INFUSE bone graft, containing BMP-2 on a collagen sponge, will be wrapped around the tibia during the surgical process.

Treatment: Surgery: Control Group
The control group will receive the standard surgical protocol, without addition of the INFUSE device.
Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
RUST Score
Timepoint [1] 0 0
12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing and is the score reported.
Secondary outcome [1] 0 0
Average Time to Healing in Months
Timepoint [1] 0 0
Baseline through 12 months post-surgery.
Secondary outcome [2] 0 0
Refracture Rate
Timepoint [2] 0 0
12 months post-surgery
Secondary outcome [3] 0 0
Long-term Refracture
Timepoint [3] 0 0
annually, up to 10 years post-surgery
Secondary outcome [4] 0 0
Ten Meter Timed Walk
Timepoint [4] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [5] 0 0
Pain Intensity
Timepoint [5] 0 0
measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery
Secondary outcome [6] 0 0
Quality of Life Score - The Upper Extremity and Physical Function Core Scale
Timepoint [6] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [7] 0 0
Quality of Life Score - The Transfer and Basic Mobility Core Scale
Timepoint [7] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [8] 0 0
Quality of Life Score - The Sports and Physical Functioning Core Scale
Timepoint [8] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [9] 0 0
Quality of Life Score - The Pain/Comfort Core Scale
Timepoint [9] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [10] 0 0
Quality of Life Score - The Happiness Core Scale
Timepoint [10] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.
Secondary outcome [11] 0 0
Quality of Life Score - The Global Functioning Scale
Timepoint [11] 0 0
Assessed at 6 and 12 months after surgery. Month 12 reported.

Eligibility
Key inclusion criteria
* Diagnosis of NF1 using the NIH Consensus Conference criteria. In addition to tibial pseudarthrosis, one or more of the following diagnostic criteria for NF1 must be present:
* Six or more cafe'-au-lait spots (= 0.5cm prepubertal; = 1.5cm postpubertal)
* Freckling in the axilla or groin Optic pathway glioma
* Two or more iris Lisch nodules
* Two or more neurofibromas or one plexiform neurofibroma
* A first-degree relative with NF1
* Patients must have tibial pseudarthrosis that has the potential to cause significant morbidity. Radiographic findings (AP & lateral leg radiographs) must support the diagnosis of tibial pseudarthrosis with chronic non-union.
* Age between 2 years and 18 years of age at time of study entry.
* Performance Level: Karnofsky = 50 percent for patients > 10 years of age and Lansky = 50 percent for patients or = 10 years of age.

Prior Therapy:

* Patients who have undergone 1 previous surgery for tibial pseudarthrosis repair will be eligible to enter the study if they have refracture.
* Use of BMP-2 in the prior surgery is permitted, however patients with prior exposure must be screened for antibodies to BMP-2, bovine collagen, and rhBMP-2 neutralizing antibodies.
* Prior use of BMP-2 is allowed but will be recorded as a possible compounding factor.
* Patients who have had 2 or more prior surgeries for pseudarthrosis repair are ineligible

Absence of Tumors:

* Patients must undergo thorough physical examination of the leg undergoing surgery. If physical exam is equivocal for presence of tumors, then a normal MRI of the lower extremity will be required before eligibility is met.
* If there is evidence of plexiform neurofibroma or nodular neurofibroma of > 3 cm diameter on the ipsilateral leg, then they are ineligible for the study.
* Organ Function Requirements
* Adequate bone marrow function defined as:

* Absolute neutrophil count (ANC) > 1500/
* µl Platelet count > 100,000/
* µl Hemoglobin = 10.0 gm/dL

Adequate renal function defined as:

* maximum serum creatinine of 1.5 mg/dL OR
* a creatinine clearance=70ml/min/1.73m2.

Adequate renal function defined as:

* maximum serum creatinine of 1.5 mg/dL OR
* a creatinine clearance = 70ml/min/1.73m2.

Adequate liver function defined as:

* Total bilirubin < 1.5 X upper limit of normal for age, and SGPT (serum glutamic pyruvic transaminase, ALT) < 2 X upper limit of normal for age
* Serum Vitamin D level = 10 ng/ml
Minimum age
2 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Lack of documentation for a diagnosis of NF1
* Tibial fracture without evidence of pseudarthrosis or tibial dysplasia
* Tibial dysplasia/bowing without fracture or pseudarthrosis
* Plexiform neurofibroma of any size, or nodular neurofibroma of > 3 cm diameter involving the ipsilateral leg, including the hip
* If presence of plexiform is suspected but not certain on physical exam, MRI of the leg may be indicated to rule this out.
* History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma
* Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree
* Visual impairment from any cause
* Precocious puberty from any cause
* Hypertension other than mild essential hypertension controlled with medication
* Metastatic disease of any kind
* Inadequate neurovascular status in the involved limb that may jeopardize healing
* Active or known prior infection at the pseudarthrosis site
* Active systemic infection
* Other injury or condition that prevents ambulation or completion of study assessments
* Two or more prior surgeries for tibial pseudarthrosis
* Bilateral tibial dysplasia
* Selection of a surgical approach that does not include prescribed surgical intervention, which must include removal of pseudarthrosis tissue, placement of an intramedullary rod using the Williams approach, and autogenous bone graft from the iliac crest distributed at the osteotomy site
* Normal ipsilateral fibula without planned fibular osteotomy at time of surgery
* Allergy to bone morphogenetic protein
* Allergy to bovine collagen products
* Positive antibody titers to BMP-2, bovine collagen, or BMP-2 neutralizing antibodies prior to surgery
* History of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: Anabolic agents, Glucocorticoids (does not include inhaled glucocorticoids), Growth hormone, Parathyroid hormone (PTH)
* Need for postoperative medications that could interfere with bone healing of the implant, such as steroids, (but not including low-dose aspirin or routine perioperative anti-inflammatory drugs)
* Untreated endocrine abnormality, such as hypothyroidism, parathyroid hormone disorder
* Severe Vitamin D deficiency with serum 25-OH (hydroxy) Vitamin D < 10 ng/ml (25 nmol/l) Patients with Vitamin D levels < 10 ng/ml may be treated with Vitamin D and reconsidered for enrollment when levels are sufficient
* Females who are sexually active without use of effective contraception
* Females who are pregnant or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2020
Sample size
Target
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Other
Name
University of Alabama at Birmingham
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Children's Tumor Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Medtronic
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bruce R. Korf, MD, PhD
Address 0 0
Univ. of Alabama at Birmingham
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02718131