Phase 1/2a Study on Allogeneic Osteoblastic Cells Implantation in Delayed-Union Fractures

• Sponsor: Bone Therapeutics S.A (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02020590
• Collaborator: (none)
• Enrollment: 25
• Arm: 1
• Duration (Months): 71.9

Study Details

Study Description

Brief Summary

Fracture healing is a complex physiological process caused by interaction of cellular elements, cytokines and signaling proteins, which results in the formation of new bone. There is for now no universally accepted approach to evaluate the progression of fracture healing. Typically, a fracture is considered as a delayed-union when the bone has not united within a period of time that would be considered adequate for bone healing. Delayed-union suggests that union is slow but will eventually occur without additional surgical or non-surgical intervention, whereas non-union is defined as the cessation of all reparative process of healing.

The incidence of impaired healing is estimated to range from 5 to 10% of all long bone fractures, depending on the fracture site, the type and degree of injury, among other factors. Currently the treatment of choice remains bone allograft or autograft. This procedure shows in general good results but requires an invasive surgery of several hours under general anesthesia, followed by a few days of hospitalization. Because of this, major complications have been reported in up to 20-30% of patients.

The present Phase 1/2a study aims at demonstrating the safety and efficacy of ALLOB®, a proprietary population of allogeneic osteoblastic cells, in the treatment of delayed-union fractures of long bones. In this study, delayed-union is defined at the time of screening as an absence of healing of minimum 3 months and maximum 7 months (+/- 2 weeks) after the onset of the fracture.

Condition or Disease	Intervention/Treatment	Phase
Long Bone Delayed-Union Fracture	Drug: ALLOB® implantation	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Phase 1/2a, Multicentre, Open Proof-of-concept Study on the Efficacy and Safety of Allogeneic Osteoblastic Cells (ALLOB®) Implantation in Non-infected Delayed-Union Fractures
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Jan 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALLOB® Implantation One arm: ALLOB® Implantation	Drug: ALLOB® implantation; Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.

Outcome Measures

Primary Outcome Measures

1. Percentage of Responders at 6 Months (Efficacy of ALLOB) [6 months]

   The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under treatment if, at Month 6: - He/she had a rescue surgery Or - The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the Tomographic Union Score (TUS) as assessed by CT scan has not increased by at least two points (versus baseline).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient (or patient's legally acceptable representative) capable to provide a written, dated, and signed informed consent prior to any study related procedure

• Non-infected delayed-union fracture of a long bone of minimum 3 months and maximum 7 months (+/- 2 weeks)

Exclusion Criteria:

• Fracture interline larger than 2.5 cm

• Insufficient fracture stability

• Multifocal fracture

• Positive serology for hepatitis B, hepatitis C, Human Immunodeficiency Virus (HIV)

• Current or past medical disease that could interfere with the evaluation of the safety and efficacy, as judged by the investigator

• Severe renal or hepatic impairment

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Bone Therapeutics S.A

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 2, 2017

More Information

Publications

None provided.

• Responsible Party: Bone Therapeutics S.A
• ClinicalTrials.gov Identifier: NCT02020590
• Other Study ID Numbers: ALLOB-DU1
• First Posted: Dec 25, 2013
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• Keywords provided by Bone Therapeutics S.A: Delayed-Union Fractures; Impaired Healing; Fractures; Orthopedics; Bone; Musculoskeletal Disorders
• Additional relevant MeSH terms: Fractures, Bone; Fractures, Ununited

Study Results

Participant Flow

Pre-assignment Detail	Of the 25 patients enrolled in the study (ICF signature), 22 patients were treated: 2 patients were considered as non eligible before treatment 1 patient withdrew consent before prior to Day 0

Arm/Group Title	ALLOB® Implantation
Arm/Group Description	One arm: ALLOB® Implantation ALLOB® implantation: Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ALLOB® Implantation
Arm/Group Description	One arm: ALLOB® Implantation ALLOB® implantation: Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (13.96)
Sex: Female, Male (Count of Participants)
Female	9 40.9%
Male	13 59.1%
Race/Ethnicity, Customized (Count of Participants)
Caucasian/White	22 100%
Region of Enrollment (participants) [Number]
Belgium	13 59.1%
Germany	9 40.9%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.73 (4.676)

Outcome Measures

1. Primary Outcome

Title	Percentage of Responders at 6 Months (Efficacy of ALLOB)
Description	The success of the study will be based on the percentage of treated patients (ALLOB®) not failing under treatment. A patient will be considered as failed under treatment if, at Month 6: - He/she had a rescue surgery Or - The Global Disease Evaluation score (VAS) as perceived by the patient has not improved by at least 25% and the Tomographic Union Score (TUS) as assessed by CT scan has not increased by at least two points (versus baseline).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

The efficacy analysis was conducted on the Per Protocol population (21 treated patients; one patient being excluded from the analysis due on a major protocol deviation)

Arm/Group Title	ALLOB® Implantation
Arm/Group Description	One arm: ALLOB® Implantation ALLOB® implantation: Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.
Measure Participants	21
Number (90% Confidence Interval) [percent of patients]	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALLOB® Implantation
	Comments	The success of ALLOB® treatment was based on the percentage of responders. A treated patient was considered as responding if, at the end of the study (6 months): He/she had not required rescue surgery and The GDE score as perceived by the patient had improved by at least 25% or the TUS (tomographic union score) as assessed by CT scan had increased by at least 2 points.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		The response rate at Month 6 for the 21 patients in the PP population was 100 % (CI: 86.71 - 100.0%). None of the treated patients required rescue surgery. An improvement of GDE score of at least 25% was reported for 16 (76.2%) patients. An increase in TUS of at least 2 points was reported for 16 (76.2%) patients; all patients met at least one of these two criteria.

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Emergence was defined from the date of ALLOB® implantation up to end of study visit (Month-6 visit)
Arm/Group Title	ALLOB® Implantation
Arm/Group Description	One arm: ALLOB® Implantation ALLOB® implantation: Each patient will undergo a single administration of ALLOB® into the delayed-union site under anesthesia.
All Cause Mortality
	ALLOB® Implantation
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Serious Adverse Events
	ALLOB® Implantation
	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)
Infections and infestations
implant site infection	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
angioedema	1/22 (4.5%)	1
Urticaria	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	ALLOB® Implantation
	Affected / at Risk (%)	# Events
Total	9/22 (40.9%)
Injury, poisoning and procedural complications
Fall	2/22 (9.1%)	2
Procedural pain	5/22 (22.7%)	5
Metabolism and nutrition disorders
Vitamin D Deficiency	2/22 (9.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.