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

Osteogenesis Imperfecta Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04623606
• Other study ID #: CMCB2B0X
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 20, 2019
• Est. completion date: December 2021

Study information

• Verified date: November 2020
• Source: Christian Medical College, Vellore, India
• Contact: Vrisha Madhuri, MS Orth
• Phone: 91-416-2282172
• Email: madhuriwalter[@]cmcvellore.ac.in
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2021
• Est. primary completion date: November 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 8 Years

Eligibility

(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

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

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

Locations

Country	Name	City	State
India	Christian Medical College	Vellore	Tamil Nadu

Sponsors (4)

Lead Sponsor	Collaborator
Christian Medical College, Vellore, India	Karolinska Institutet, Ministry of Science and Technology, India, Vinnova

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Impact on the subjects Quality of Life: Pediatric Quality of Life Questionnaire™ (PedsQOL) [ Time Frame: From baseline to the 16 month follow-up	Quality of life assessed using the Infant Pediatric Quality of Life Questionnaire™ (PedsQOL).	From baseline to 16 months follow up
Other	Incidence of donor cells engrafted into patient tissue samples assessed by histology. [ Time Frame: From baseline to the 16 month follow up	Donor cell engraftment.	From baseline to 16 months follow up
Other	Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects. [ Time Frame: From baseline to the 16 month follow up	Paracrine effects will be analysed from plasma isolated from peripheral blood.	From baseline to 16 months follow up
Primary	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	From baseline to 16 months follow up
Secondary	Number of fractures [ Time Frame: From baseline to 16 months follow-up ]	Number of fractures.	From baseline to 16 months follow up
Secondary	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	From baseline to 16 months follow up
Secondary	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).	From baseline to 16 months follow up
Secondary	Growth (cm). [ Time Frame: From baseline to16 months follow up]	Growth (cm) as assessed by clinician	From baseline to 16 months follow up
Secondary	Weight (kg). [ Time Frame: From baseline to 16 months follow up]	Growth (kg) as assessed by clinician.	From baseline to 16 months follow up
Secondary	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.	From baseline to 16 months follow up
Secondary	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 %)	From at baseline to 16 months follow up
Secondary	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 %)	From baseline to 16 months follow up
Secondary	Assessment of biochemical bone turnover by analysis of the markers P-Albumin (g/dL)	Assessment of biochemical bone turnover marker P-Albumin (g/dL)	From baseline to 16 months follow up
Secondary	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)	From baseline to 16 months follow up
Secondary	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 %)	From baseline to 16 months follow up
Secondary	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)	From baseline to 16 months follow up
Secondary	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)	From baseline to 16 months follow up
Secondary	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)	From baseline to 16 months follow up
Secondary	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)	From baseline to 16 months follow up
Secondary	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 %)	From baseline to 16 months follow up

External Links

•   Boost to Brittle Bones