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Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones (BOOST2B)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04623606
Recruitment Status : Unknown
Verified November 2020 by Vrisha Madhuri, Christian Medical College, Vellore, India.
Recruitment status was:  Recruiting
First Posted : November 10, 2020
Last Update Posted : November 10, 2020
Sponsor:
Collaborators:
Ministry of Science and Technology, India
Vinnova
Karolinska Institutet
Information provided by (Responsible Party):
Vrisha Madhuri, Christian Medical College, Vellore, India

Study Description
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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.

Condition or disease Intervention/treatment Phase
Osteogenesis Imperfecta Biological: BOOST cells Phase 1 Phase 2

Study Design
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Study Type : Interventional
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Historical and Untreated prospective control and Treatment group
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 20, 2019
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
No Intervention: Prospective Control (Untreated) and historical controls
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
Experimental: Treatment
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.
 Biological: BOOST cells
Four doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells.


Outcome Measures
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Primary Outcome Measures :
  1. Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs) [ Time Frame: From baseline to 16 months follow up ]

    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:

    1. Vital signs in conjunction with the MSC infusion
    2. Transfusion reactions (infusion toxicity, embolism, allergy, infections)
    3. Immune reaction towards the cells, donor-specific antibodies, graft rejection, Graft versus Host Disease, autoimmunity)
    4. Tumourigenicity
    5. Mortality/morbidity


Secondary Outcome Measures :
  1. Number of fractures [ Time Frame: From baseline to 16 months follow-up ] [ Time Frame: From baseline to 16 months follow up ]
    Number of fractures.

  2. 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 Frame: From baseline to 16 months follow up ]
    Time (days) to first fracture after each stem cell administration. Number of fractures

  3. Change in bone-marrow density (g/cm2). [ Time Frame: From baseline to the primary follow-up (From baseline to 16 months follow up) [ Time Frame: From baseline to 16 months follow up ]
    Change in bone-marrow density (g/cm2).

  4. Growth (cm). [ Time Frame: From baseline to16 months follow up] [ Time Frame: From baseline to 16 months follow up ]
    Growth (cm) as assessed by clinician

  5. Weight (kg). [ Time Frame: From baseline to 16 months follow up] [ Time Frame: From baseline to 16 months follow up ]
    Growth (kg) as assessed by clinician.

  6. Change in clinical status of OI. [ Time Frame: From baseline to 16 months follow up] [ 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.

  7. Assessment of biochemical bone turnover by analysis of the markers P-Calcium (mg %) in blood samples. [ Time Frame: From at baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker P-Calcium (mg %)

  8. Assessment of biochemical bone turnover by analysis of the markers P-Phosphate (mg %) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker P-Phosphate (mg %)

  9. Assessment of biochemical bone turnover by analysis of the markers P-Albumin (g/dL) [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker P-Albumin (g/dL)

  10. Assessment of biochemical bone turnover by analysis of the markers S-ALP (IU/L) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker S-ALP (IU/L)

  11. Assessment of biochemical bone turnover by analysis of the markers S-CTx (mg %) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker S-CTx (mg %)

  12. Assessment of biochemical bone turnover by analysis of the markers fP-PTH (pg/mL)in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker fP-PTH (pg/mL)

  13. Assessment of biochemical bone turnover by analysis of the markers Vitamin D (nmol/L) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker Vitamin D (nmol/L)

  14. Assessment of biochemical bone turnover by analysis of the markers Bone specific S-ALP (μg/L) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker Bone specific S-ALP (μg/L)

  15. Assessment of biochemical bone turnover by analysis of the markers S-Osteocalcin (ng/mL) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker S-Osteocalcin (ng/mL)

  16. Assessment of biochemical bone turnover by analysis of the markers U-DPD/Krea and U-NTx/Krea (mg %) in blood samples. [ Time Frame: From baseline to 16 months follow up ]
    Assessment of biochemical bone turnover marker U-DPD/Krea and U-NTx/Krea (mg %)


Other Outcome Measures:
  1. Impact on the subjects Quality of Life: Pediatric Quality of Life Questionnaire™ (PedsQOL) [ Time Frame: From baseline to the 16 month follow-up [ Time Frame: From baseline to 16 months follow up ]
    Quality of life assessed using the Infant Pediatric Quality of Life Questionnaire™ (PedsQOL).

  2. Incidence of donor cells engrafted into patient tissue samples assessed by histology. [ Time Frame: From baseline to the 16 month follow up [ Time Frame: From baseline to 16 months follow up ]
    Donor cell engraftment.

  3. Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects. [ Time Frame: From baseline to the 16 month follow up [ Time Frame: From baseline to 16 months follow up ]
    Paracrine effects will be analysed from plasma isolated from peripheral blood.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

(i)Inclusion Criteria Treatment group

  1. Parent's/legal guardian's signed informed-consent form
  2. Clinical diagnosis of OI type III or IV AND
  3. Molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
  4. Age between 1 to 4 years
  5. BP treatment initiated before inclusion
  6. Parent/legal guardian over 18 years of age

(ii)Inclusion Criteria Prospective Untreated Control Group and Historical Control Group:

  1. Parent's/legal guardian's signed informed-consent form
  2. Clinical and molecular diagnosis of OI (Glycine substitution in the collagen triple-helix encoding region of either the COL1A1 or COL1A2 gene)
  3. Age between 4 to 8 years
  4. Parent/legal guardian over 18 years of age

(iii)Exclusion Criteria Treatment group Prospective and historical control group:

  1. 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
  2. Any contraindication for invasive procedures such as a moderate/severe bleeding tendency or contagious infections
  3. Abnormal karyotype or other confirmed genetic syndromes
  4. Oncologic disease
  5. Inability to comply with the trial protocol and evaluation and follow-up schedule
  6. Inability to understand the information and to provide informed consent
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04623606


Contacts
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Contact: Vrisha Madhuri, MS Orth 91-416-2282172 madhuriwalter@cmcvellore.ac.in
Contact: Suhasini Ganesh, M.Pharm 91-416-2285117 brittlebonekids@cmcvellore.ac.in

Locations
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India
Christian Medical College Recruiting
Vellore, Tamil Nadu, India, 632004
Contact: Suhasini Ganesh, M.Pharm    91-416-2285117    brittlebonekids@cmcvellore.ac.in   
Contact: Suhasini Ganesh, M Pharm    91-416-2285117    brittlebonekids@cmcvellore.ac.in   
Sponsors and Collaborators
Christian Medical College, Vellore, India
Ministry of Science and Technology, India
Vinnova
Karolinska Institutet
Investigators
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Principal Investigator: Vrisha Madhuri, MS Orth Christian Medical College, Vellore, India
More Information
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Additional Information:

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Responsible Party: Vrisha Madhuri, Professor, Christian Medical College, Vellore, India
ClinicalTrials.gov Identifier: NCT04623606    
Other Study ID Numbers: CMCB2B0X
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vrisha Madhuri, Christian Medical College, Vellore, India:
OI, Brittle bone disease
Hereditary bone fragility
Additional relevant MeSH terms:
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Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
 Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases