Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones

NCT04623606 | Unknown Phase 1 DMC

• 1 other identifier: CMCB2B0X
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteogenesis Imperfecta

Keywords

OI, Brittle bone disease; Hereditary bone fragility

Outcome Measures

Primary Outcomes (1)

• 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: 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

  From baseline to 16 months follow up

Secondary Outcomes (16)

• Number of fractures [ Time Frame: From baseline to 16 months follow-up ]

  From baseline to 16 months follow up

• 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.

  From baseline to 16 months follow up

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

  From baseline to 16 months follow up

• Growth (cm). [ Time Frame: From baseline to16 months follow up]

  From baseline to 16 months follow up

• Weight (kg). [ Time Frame: From baseline to 16 months follow up]

  From baseline to 16 months follow up

Other Outcomes (3)

• Impact on the subjects Quality of Life: Pediatric Quality of Life Questionnaire™ (PedsQOL) [ Time Frame: From baseline to the 16 month follow-up

  From baseline to 16 months follow up

• Incidence of donor cells engrafted into patient tissue samples assessed by histology. [ Time Frame: From baseline to the 16 month follow up

  From baseline to 16 months follow up

• Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects. [ Time Frame: From baseline to the 16 month follow up

  From baseline to 16 months follow up

Study Arms (2)

Prospective Control (Untreated) and historical controls

NO INTERVENTION

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

Treatment

EXPERIMENTAL

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

Interventions

BOOST cells BIOLOGICAL

Four doses of expanded human 1st trimester fetal liver-derived mesenchymal stem cells.

Treatment

Eligibility Criteria

• Age: 1 Year - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• Parent/legal guardian over 18 years of age
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Christian Medical College, Vellore, India: lead
• Ministry of Science and Technology, India: collaborator
• Vinnova: collaborator
• Karolinska Institutet: collaborator

Study Sites (1)

Christian Medical College

Vellore, Tamil Nadu, 632004, India

RECRUITING

MeSH Terms

Conditions

Osteogenesis Imperfecta

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Vrisha Madhuri, MS Orth

  Christian Medical College, Vellore, India

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vrisha Madhuri, MS Orth

CONTACT

91-416-2282172; madhuriwalter@cmcvellore.ac.in

Suhasini Ganesh, M.Pharm

CONTACT

91-416-2285117; brittlebonekids@cmcvellore.ac.in

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Historical and Untreated prospective control and Treatment group

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: November 10, 2020
• Study Start: May 20, 2019
• Primary Completion: November 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 10, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)