Back to resultsBoost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones (BOOST2B)
Primary Purpose
Osteogenesis Imperfecta
Status
Unknown status
Phase
Phase 1
Locations
India
Study Type
Interventional
Intervention
BOOST cells
Sponsored by
About this trial
This is an interventional treatment trial for Osteogenesis Imperfecta focused on measuring OI, Brittle bone disease, Hereditary bone fragility
Eligibility Criteria
(i)Inclusion Criteria Treatment group
- Parent's/legal guardian's signed informed-consent form
- Clinical diagnosis of OI type III or IV AND
- Molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
- Age between 1 to 4 years
- BP treatment initiated before inclusion
- Parent/legal guardian over 18 years of age
(ii)Inclusion Criteria Prospective Untreated Control Group and Historical Control Group:
- Parent's/legal guardian's signed informed-consent form
- Clinical and molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
- Age between 4 to 8 years
- Parent/legal guardian over 18 years of age
(iii)Exclusion Criteria Treatment group Prospective and historical control group:
- Existence of other known disorder that might interfere with the treatment (such as severe malformations, congenital heart defect, hypoxic encephalopathy (l-lll), neurological problems, immune deficiencies, muscle diseases, syndromes) diagnosed by clinical examination
- Any contraindication for invasive procedures such as a moderate/severe bleeding tendency or contagious infections
- Abnormal karyotype or other confirmed genetic syndromes
- Oncologic disease
- Inability to comply with the trial protocol and evaluation and follow-up schedule
- Inability to understand the information and to provide informed consent
Sites / Locations
- Christian Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Prospective Control (Untreated) and historical controls
Treatment
Arm Description
Subjects eligible for the trial but not willing/able to participate in any of the experimental arms Matched historical controls. Subjects will be identified in historical registries and data will be retrieved from OI database
Administration of four doses of BOOST cells with the first dose between 1-4 years of age and the three additional doses at +4, +8 and +12 months after the first dose. Each dose is 3x10^6 MSC/kg body weight.
Outcomes
Primary Outcome Measures
Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs)
The primary endpoint is safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs)/Serious AE (SAE)/Suspected Unexpected Serious Adverse Reaction (SUSAR)with specific focus on the following:
Vital signs in conjunction with the MSC infusion
Transfusion reactions (infusion toxicity, embolism, allergy, infections)
Immune reaction towards the cells, donor-specific antibodies, graft rejection, Graft versus Host Disease, autoimmunity)
Tumourigenicity
Mortality/morbidity
Secondary Outcome Measures
Number of fractures [ Time Frame: From baseline to 16 months follow-up ]
Number of fractures.
Time (days) to first fracture after each stem cell administration. [ Time Frame: From each dose of stem cells to the time point of the first fracture.
Time (days) to first fracture after each stem cell administration. Number of fractures
Change in bone-marrow density (g/cm2). [ Time Frame: From baseline to the primary follow-up (From baseline to 16 months follow up)
Change in bone-marrow density (g/cm2).
Growth (cm). [ Time Frame: From baseline to16 months follow up]
Growth (cm) as assessed by clinician
Weight (kg). [ Time Frame: From baseline to 16 months follow up]
Growth (kg) as assessed by clinician.
Change in clinical status of OI. [ Time Frame: From baseline to 16 months follow up]
Change in clinical status of OI based on parameters defined under efficacy assessments described in protocol, as assessed by OI clinician.
Assessment of biochemical bone turnover by analysis of the markers P-Calcium (mg %) in blood samples.
Assessment of biochemical bone turnover marker P-Calcium (mg %)
Assessment of biochemical bone turnover by analysis of the markers P-Phosphate (mg %) in blood samples.
Assessment of biochemical bone turnover marker P-Phosphate (mg %)
Assessment of biochemical bone turnover by analysis of the markers P-Albumin (g/dL)
Assessment of biochemical bone turnover marker P-Albumin (g/dL)
Assessment of biochemical bone turnover by analysis of the markers S-ALP (IU/L) in blood samples.
Assessment of biochemical bone turnover marker S-ALP (IU/L)
Assessment of biochemical bone turnover by analysis of the markers S-CTx (mg %) in blood samples.
Assessment of biochemical bone turnover marker S-CTx (mg %)
Assessment of biochemical bone turnover by analysis of the markers fP-PTH (pg/mL)in blood samples.
Assessment of biochemical bone turnover marker fP-PTH (pg/mL)
Assessment of biochemical bone turnover by analysis of the markers Vitamin D (nmol/L) in blood samples.
Assessment of biochemical bone turnover marker Vitamin D (nmol/L)
Assessment of biochemical bone turnover by analysis of the markers Bone specific S-ALP (μg/L) in blood samples.
Assessment of biochemical bone turnover marker Bone specific S-ALP (μg/L)
Assessment of biochemical bone turnover by analysis of the markers S-Osteocalcin (ng/mL) in blood samples.
Assessment of biochemical bone turnover marker S-Osteocalcin (ng/mL)
Assessment of biochemical bone turnover by analysis of the markers U-DPD/Krea and U-NTx/Krea (mg %) in blood samples.
Assessment of biochemical bone turnover marker U-DPD/Krea and U-NTx/Krea (mg %)
Full Information
NCT ID
NCT04623606
First Posted
September 18, 2020
Last Updated
November 6, 2020
Sponsor
Christian Medical College, Vellore, India
Collaborators
Ministry of Science and Technology, India, Vinnova, Karolinska Institutet
1. Study Identification
Unique Protocol Identification Number
NCT04623606
Brief Title
Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
Acronym
BOOST2B
Official Title
Exploratory, Open Label, Multiple Dose, Phase I/II Trial Evaluating Safety, Efficacy of Intravenous and Intraosseous Infusion of Allogeneic Fetal Mesenchymal Stem In Treatment of Severe Osteogenesis Imperfecta Compared With Historical and Untreated Prospective Controls
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 20, 2019 (Actual)
Primary Completion Date
November 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Christian Medical College, Vellore, India
Collaborators
Ministry of Science and Technology, India, Vinnova, Karolinska Institutet
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An exploratory, open label, multiple dose, phase I/II trial (n=15) evaluating safety and efficacy of intravenous and intraosseous infusion of allogeneic expanded fetal mesenchymal stem cells (MSC) for the treatment of severe Osteogenesis Imperfecta (OI) compared with historical and untreated prospective controls.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteogenesis Imperfecta
Keywords
OI, Brittle bone disease, Hereditary bone fragility
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Historical and Untreated prospective control and Treatment group
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prospective Control (Untreated) and historical controls
Arm Type
No Intervention
Arm Description
Subjects eligible for the trial but not willing/able to participate in any of the experimental arms Matched historical controls. Subjects will be identified in historical registries and data will be retrieved from OI database
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Administration of four doses of BOOST cells with the first dose between 1-4 years of age and the three additional doses at +4, +8 and +12 months after the first dose. Each dose is 3x10^6 MSC/kg body weight.
Intervention Type
Biological
Intervention Name(s)
BOOST cells
Intervention Description
Four doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells.
Primary Outcome Measure Information:
Title
Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs)
Description
The primary endpoint is safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs)/Serious AE (SAE)/Suspected Unexpected Serious Adverse Reaction (SUSAR)with specific focus on the following:
Vital signs in conjunction with the MSC infusion
Transfusion reactions (infusion toxicity, embolism, allergy, infections)
Immune reaction towards the cells, donor-specific antibodies, graft rejection, Graft versus Host Disease, autoimmunity)
Tumourigenicity
Mortality/morbidity
Time Frame
From baseline to 16 months follow up
Secondary Outcome Measure Information:
Title
Number of fractures [ Time Frame: From baseline to 16 months follow-up ]
Description
Number of fractures.
Time Frame
From baseline to 16 months follow up
Title
Time (days) to first fracture after each stem cell administration. [ Time Frame: From each dose of stem cells to the time point of the first fracture.
Description
Time (days) to first fracture after each stem cell administration. Number of fractures
Time Frame
From baseline to 16 months follow up
Title
Change in bone-marrow density (g/cm2). [ Time Frame: From baseline to the primary follow-up (From baseline to 16 months follow up)
Description
Change in bone-marrow density (g/cm2).
Time Frame
From baseline to 16 months follow up
Title
Growth (cm). [ Time Frame: From baseline to16 months follow up]
Description
Growth (cm) as assessed by clinician
Time Frame
From baseline to 16 months follow up
Title
Weight (kg). [ Time Frame: From baseline to 16 months follow up]
Description
Growth (kg) as assessed by clinician.
Time Frame
From baseline to 16 months follow up
Title
Change in clinical status of OI. [ Time Frame: From baseline to 16 months follow up]
Description
Change in clinical status of OI based on parameters defined under efficacy assessments described in protocol, as assessed by OI clinician.
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers P-Calcium (mg %) in blood samples.
Description
Assessment of biochemical bone turnover marker P-Calcium (mg %)
Time Frame
From at baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers P-Phosphate (mg %) in blood samples.
Description
Assessment of biochemical bone turnover marker P-Phosphate (mg %)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers P-Albumin (g/dL)
Description
Assessment of biochemical bone turnover marker P-Albumin (g/dL)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers S-ALP (IU/L) in blood samples.
Description
Assessment of biochemical bone turnover marker S-ALP (IU/L)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers S-CTx (mg %) in blood samples.
Description
Assessment of biochemical bone turnover marker S-CTx (mg %)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers fP-PTH (pg/mL)in blood samples.
Description
Assessment of biochemical bone turnover marker fP-PTH (pg/mL)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers Vitamin D (nmol/L) in blood samples.
Description
Assessment of biochemical bone turnover marker Vitamin D (nmol/L)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers Bone specific S-ALP (μg/L) in blood samples.
Description
Assessment of biochemical bone turnover marker Bone specific S-ALP (μg/L)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers S-Osteocalcin (ng/mL) in blood samples.
Description
Assessment of biochemical bone turnover marker S-Osteocalcin (ng/mL)
Time Frame
From baseline to 16 months follow up
Title
Assessment of biochemical bone turnover by analysis of the markers U-DPD/Krea and U-NTx/Krea (mg %) in blood samples.
Description
Assessment of biochemical bone turnover marker U-DPD/Krea and U-NTx/Krea (mg %)
Time Frame
From baseline to 16 months follow up
Other Pre-specified Outcome Measures:
Title
Impact on the subjects Quality of Life: Pediatric Quality of Life Questionnaire™ (PedsQOL) [ Time Frame: From baseline to the 16 month follow-up
Description
Quality of life assessed using the Infant Pediatric Quality of Life Questionnaire™ (PedsQOL).
Time Frame
From baseline to 16 months follow up
Title
Incidence of donor cells engrafted into patient tissue samples assessed by histology. [ Time Frame: From baseline to the 16 month follow up
Description
Donor cell engraftment.
Time Frame
From baseline to 16 months follow up
Title
Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects. [ Time Frame: From baseline to the 16 month follow up
Description
Paracrine effects will be analysed from plasma isolated from peripheral blood.
Time Frame
From baseline to 16 months follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
(i)Inclusion Criteria Treatment group
Parent's/legal guardian's signed informed-consent form
Clinical diagnosis of OI type III or IV AND
Molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
Age between 1 to 4 years
BP treatment initiated before inclusion
Parent/legal guardian over 18 years of age
(ii)Inclusion Criteria Prospective Untreated Control Group and Historical Control Group:
Parent's/legal guardian's signed informed-consent form
Clinical and molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
Age between 4 to 8 years
Parent/legal guardian over 18 years of age
(iii)Exclusion Criteria Treatment group Prospective and historical control group:
Existence of other known disorder that might interfere with the treatment (such as severe malformations, congenital heart defect, hypoxic encephalopathy (l-lll), neurological problems, immune deficiencies, muscle diseases, syndromes) diagnosed by clinical examination
Any contraindication for invasive procedures such as a moderate/severe bleeding tendency or contagious infections
Abnormal karyotype or other confirmed genetic syndromes
Oncologic disease
Inability to comply with the trial protocol and evaluation and follow-up schedule
Inability to understand the information and to provide informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vrisha Madhuri, MS Orth
Phone
91-416-2282172
Email
madhuriwalter@cmcvellore.ac.in
First Name & Middle Initial & Last Name or Official Title & Degree
Suhasini Ganesh, M.Pharm
Phone
91-416-2285117
Email
brittlebonekids@cmcvellore.ac.in
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vrisha Madhuri, MS Orth
Organizational Affiliation
Christian Medical College, Vellore, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
Christian Medical College
City
Vellore
State/Province
Tamil Nadu
ZIP/Postal Code
632004
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suhasini Ganesh, M.Pharm
Phone
91-416-2285117
Email
brittlebonekids@cmcvellore.ac.in
First Name & Middle Initial & Last Name & Degree
Suhasini Ganesh, M Pharm
Phone
91-416-2285117
Email
brittlebonekids@cmcvellore.ac.in
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://boost2b.in/
Description
Boost to Brittle Bones
Learn more about this trial
Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
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