Clinical trial NCT04623606: Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Osteogenesis Imperfecta
Keywords: OI, Brittle bone disease
Hereditary bone fragility
Lead sponsor: Christian Medical College, Vellore, India
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, India
name: Vinnova
name: Karolinska Institutet
First posted: 2020-11-10
Enrollment: 15
Sex: ALL
Minimum age (years): 1
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Historical and Untreated prospective control and Treatment group
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Safety and tolerability measured as seriousness, severity and frequency of treatment related adverse events (AEs)
timeFrame: From baseline to 16 months follow up
Secondary outcomes:
measure: Number of fractures [ Time Frame: From baseline to 16 months follow-up ]
timeFrame: From baseline to 16 months follow up
measure: 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.
timeFrame: From baseline to 16 months follow up
measure: Change in bone-marrow density (g/cm2). [ Time Frame: From baseline to the primary follow-up (From baseline to 16 months follow up)
timeFrame: From baseline to 16 months follow up
measure: Growth (cm). [ Time Frame: From baseline to16 months follow up]
timeFrame: From baseline to 16 months follow up
measure: Weight (kg). [ Time Frame: From baseline to 16 months follow up]
timeFrame: From baseline to 16 months follow up
measure: Change in clinical status of OI. [ Time Frame: From baseline to 16 months follow up]
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers P-Calcium (mg %) in blood samples.
timeFrame: From at baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers P-Phosphate (mg %) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers P-Albumin (g/dL)
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers S-ALP (IU/L) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers S-CTx (mg %) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers fP-PTH (pg/mL)in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers Vitamin D (nmol/L) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers Bone specific S-ALP (μg/L) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers S-Osteocalcin (ng/mL) in blood samples.
timeFrame: From baseline to 16 months follow up
measure: Assessment of biochemical bone turnover by analysis of the markers U-DPD/Krea and U-NTx/Krea (mg %) in blood samples.
timeFrame: From baseline to 16 months follow up
Other outcomes:
measure: Impact on the subjects Quality of Life: Pediatric Quality of Life Questionnaire™ (PedsQOL) [ Time Frame: From baseline to the 16 month follow-up
timeFrame: From baseline to 16 months follow up
measure: Incidence of donor cells engrafted into patient tissue samples assessed by histology. [ Time Frame: From baseline to the 16 month follow up
timeFrame: From baseline to 16 months follow up
measure: Analysis of an array of cytokines and micro vesicles to evaluate paracrine effects. [ Time Frame: From baseline to the 16 month follow up
timeFrame: From baseline to 16 months follow up
Locations:
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
Study officials:
affiliation: Christian Medical College, Vellore, India
name: Vrisha Madhuri, MS Orth
role: PRINCIPAL_INVESTIGATOR
References: