NCT02718131: NF107-BMP2

A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)

Terminated NA Results posted Last updated 27 October 2021

What this trial tests

NA trial testing INFUSE Bone Graft (BMP-2) in NF1 in 5 participants. Terminated before completion.

Timeline

1 March 2016

Primary endpoint
1 June 2020

1 June 2020

Quick facts

Lead sponsor	University of Alabama at Birmingham
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	5
Start date	1 March 2016
Primary completion	1 June 2020
Estimated completion	1 June 2020
Sites	16 locations across United States, Australia

Drugs / interventions tested

• INFUSE Bone Graft (BMP-2)
• Control Group — full drug profile →

Conditions studied

• NF1 — all drugs for NF1 →
• Congenital Pseudarthrosis of Tibia — all drugs for Congenital Pseudarthrosis of Tibia →

Sponsor

University of Alabama at Birmingham

Who can join

Adults 2 to 18, any sex, with NF1 or Congenital Pseudarthrosis of Tibia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

RUST Score Primary · 12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing and is the score reported.

The RUST scale (Radiographic Union Score for Tibial fractures; RUST) was developed in 2010 as a measure of tibial fracture healing and has been validated in the NF1 population. This was used as the primary outcome measure in this trial. The score is based on radiographic evaluation of the bone cortex based on AP (anterior-posterior) and lateral xrays. Four cortices of tibial bone seen in these views are each given a score of 1 to 3, with 1 representing no healing, 2 representing some callus present, and 3 representing healing of the bone cortex. The 4 scores are totaled, to give a total score

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	12	12 – 12

Average Time to Healing in Months Secondary · Baseline through 12 months post-surgery.

Time to healing is determined by RUST scores calculated at 3 month intervals after surgery. The first time point at which a score of 9 to 12 is achieved on the RUST Scale will be considered the time to complete healing. One time point is reported which is the time point of first healing.

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	4.5	3 – 6

Refracture Rate Secondary · 12 months post-surgery

Numbers of patients with refracture within 1 year after surgery.

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	0
Control Group	0

Long-term Refracture Secondary · annually, up to 10 years post-surgery

Numbers of patients with refracture over long-term follow up of up to 10 years.

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	0
Control Group	0

Ten Meter Timed Walk Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Time (seconds) to perform the Ten Meter Timed Walk. Assessed at 6 and 12 months after surgery. Both 6 month and 12 month reported.

6 month measure

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	20.2	7 – 33.3

12 month measure

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	11.3	11.3 – 11.3

Quality of Life Score - The Upper Extremity and Physical Function Core Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	76	40 – 100

Quality of Life Score - The Transfer and Basic Mobility Core Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	61	43 – 85

Quality of Life Score - The Sports and Physical Functioning Core Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	65	11 – 81

Quality of Life Score - The Pain/Comfort Core Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	75	22 – 100

Quality of Life Score - The Happiness Core Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	90	80 – 100

Quality of Life Score - The Global Functioning Scale Secondary · Assessed at 6 and 12 months after surgery. Month 12 reported.

Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower

Group	Value	95% CI
INFUSE Bone Graft (BMP-2)	65	44 – 91

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year after surgery. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

INFUSE Bone Graft (BMP-2)

Serious: 1/5 (20%)

Deaths: 0/5

Control Group

Serious: 0

Deaths: 0

Serious adverse events (1 terms)

Reaction	System	INFUSE Bone Graft (BMP-2)	Control Group
Surgical and Medical procedure - revision of Rush rod	Surgical and medical procedures	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	INFUSE Bone Graft (BMP-2)	Control Group
New fracture tibia	Musculoskeletal and connective tissue disorders	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—

Most-reported serious reactions: Surgical and Medical procedure - revision of Rush rod.

Data from ClinicalTrials.gov NCT02718131 adverse events section.

Sponsor's own description

The current study proposes adding BMP-2 (INFUSE), an anabolic agent, at the surgical site of TPA (tibial pseudarthrosis) repair in children with NF1, compared to a control group of patients treated surgically without BMP-2. The following Specific Aims will be addressed: 1) to determine if use of an osteogenic agent (BMP-2) at the time of surgical repair of TPA in NF1 patients will result in improved bone healing; 2) to document safety of BMP-2 in a pediatric NF1 population; and 3) to collect, process, and preserve biologic specimens at the time of surgery for future studies.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Supramolecular Hydrogels for Protein Delivery in Tissue Engineering.
   Lyu Y, Azevedo HS. · · 2021 · cited 37× · PMID 33562215 · DOI 10.3390/molecules26040873
2. 2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis.
   Fisher MJ, Belzberg AJ, de Blank P, De Raedt T, et al · · 2018 · cited 11× · PMID 29681099 · DOI 10.1002/ajmg.a.38675