Trial Outcomes & Findings for A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1) (NCT NCT02718131)

Results Overview

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 range of 4 to 12. For the purpose of this study, a total RUST score of 9 to 12, with at least 2 evaluable cortices having a score of 3, is considered to be healed. Scores of 5 to 8 are considered to represent partial healing, and a score of 4 is considered to be no healing.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

5 participants

Primary outcome timeframe

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

Results posted on

2021-10-27

Participant Flow

Participant milestones

Participant milestones
Measure	INFUSE Bone Graft (BMP-2) Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Overall Study STARTED	5	0
Overall Study Completed 12 Months	2	0
Overall Study COMPLETED	2	0
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	INFUSE Bone Graft (BMP-2) Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	0
Overall Study Data was incomplete. Patient was inevaluable	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing and is the score reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 range of 4 to 12. For the purpose of this study, a total RUST score of 9 to 12, with at least 2 evaluable cortices having a score of 3, is considered to be healed. Scores of 5 to 8 are considered to represent partial healing, and a score of 4 is considered to be no healing.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
RUST Score	12 score on a scale Interval 12.0 to 12.0	—

SECONDARY outcome

Timeframe: Baseline through 12 months post-surgery.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Average Time to Healing in Months	4.5 months Interval 3.0 to 6.0	—

SECONDARY outcome

Timeframe: 12 months post-surgery

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

Numbers of patients with refracture within 1 year after surgery.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Refracture Rate	0 Participants	0 Participants

SECONDARY outcome

Timeframe: annually, up to 10 years post-surgery

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=1 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Long-term Refracture	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Ten Meter Timed Walk 12 month measure	11.3 seconds Interval 11.3 to 11.3	—
Ten Meter Timed Walk 6 month measure	20.2 seconds Interval 7.0 to 33.3	—

SECONDARY outcome

Timeframe: measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery

Population: Participants were all too young to report on this scale (younger than age 4 years). No results are reported.

Pain Intensity was measured using the Faces Pain Scale-Revised (FPS-R) for patients aged 4 years and older. This is a self-report pain scale, where children chose one of 6 faces to indicate their current pain. Scores range from 0 to 10, with 0 representing no pain (happy face) and 10 representing the most pain.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Upper Extremity and Physical Function Core Scale	76 score on a scale Interval 40.0 to 100.0	—

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Transfer and Basic Mobility Core Scale	61 score on a scale Interval 43.0 to 85.0	—

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Sports and Physical Functioning Core Scale	65 score on a scale Interval 11.0 to 81.0	—

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Pain/Comfort Core Scale	75 score on a scale Interval 22.0 to 100.0	—

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Happiness Core Scale	90 score on a scale Interval 80.0 to 100.0	—

SECONDARY outcome

Timeframe: Assessed at 6 and 12 months after surgery. Month 12 reported.

Population: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

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 scores representing better quality of life.

Outcome measures

Outcome measures
Measure	INFUSE Bone Graft (BMP-2) n=2 Participants Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Quality of Life Score - The Global Functioning Scale	65 score on a scale Interval 44.0 to 91.0	—

Adverse Events

INFUSE Bone Graft (BMP-2)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	INFUSE Bone Graft (BMP-2) n=5 participants at risk Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Surgical and medical procedures Surgical and Medical procedure - revision of Rush rod	20.0% 1/5 • Number of events 1 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.	— 0/0 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.

Other adverse events

Other adverse events
Measure	INFUSE Bone Graft (BMP-2) n=5 participants at risk Standard surgery plus BMP-2	Control Group Standard surgery without BMP-2
Musculoskeletal and connective tissue disorders New fracture tibia	20.0% 1/5 • Number of events 1 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.	— 0/0 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.
Injury, poisoning and procedural complications Femur fracture	20.0% 1/5 • Number of events 1 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.	— 0/0 • 1 year after surgery The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.

Additional Information

Karen Cole-Plourde

University of Alabama at Birmingham

Phone: 205-934-5140

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	INFUSE Bone Graft (BMP-2) n=5 Participants 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. 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.	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. Control Group: The control group will receive the standard surgical protocol, without addition of the INFUSE device.	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	3.4 years STANDARD_DEVIATION 3.1 • n=5 Participants	—	3.4 years STANDARD_DEVIATION 3.1 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	—	2 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants	—	4 participants n=5 Participants
RUST score	11 scores on a scale n=5 Participants	—	11 scores on a scale n=5 Participants