Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)

NCT05559801 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00003434
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1/2 study to determine the safety and efficacy of allogeneic (third party), bone-marrow derived mesenchymal stromal cells (MSCs) for the treatment of Osteogenesis Imperfecta (OI) Type 3. It will evaluate this by looking at whether there are treatment related infusion reactions, and assessing linear growth rates and bone health, both of which are impaired in patients ages 3-10 with Osteogenesis Imperfecta Type 3. This is a single-site non-randomized clinical trial, that will take place at Children's Healthcare of Atlanta (CHOA) at Egleston and Emory Children's Center.

Conditions

Osteogenesis Imperfecta; Osteogenesis Imperfecta Type III

Outcome Measures

Primary Outcomes (16)

• Recruitment rate of participants

  Number of participants consented at the end of the trial

  Up to 24 months post-intervention

• Number of participants with correctly collected data for the study outcomes

  Number of participants with data correctly collected for the study outcomes

  Up to 24 months post-intervention

• Total number of visits with protocol deviation

  Total number of visits with protocol deviations at the end of the trial

  Up to 24 months post-intervention

• Visit attendance by participants

  Percentage of visits completed by participants

  Up to 1 year post last infusion intervention

• Patient retention rate

  Percentage of patients that complete the study intervention and all follow up study visits

  Up to 1 year post last infusion intervention

• Patient Primary Clinical Outcome Retention Rate

  Percentage of participants that completed the primary clinical outcome measurements

  Up to 1 year post last infusion intervention

• Change in acceptability from baseline

  Acceptability will be evaluated with an end of study structured, verbal interview. This interview will consist of a mix of closed ended (scaled questions from 1\[worst\]-5 \[best\]) and open-ended questions giving subjective measurements. Open-ended questions will address overall experience during the study and prompt expression of thoughts or perspectives after completing the study. The total possible score range is 18 to 90. Higher score correlates with better outcome.

  Baseline, Up to 36 months post-intervention

• Number of unexpected adverse events

  Unexpected adverse events that occur from first study intervention to one year after last infusion.

  Up to 1 year post last infusion intervention

• Number of participants with change in vital signs from baseline

  Number of participants with blood pressure, oxygen saturation, heart rate, respiratory rate, and temperature below or above each participants accepted mean reference range.

  Baseline, 10 minutes pre-intervention, 15 minutes post-intervention, 30 minutes post-intervention, 1 hour post-intervention, 1 hour post completion of the infusion

• Number of participants with changes in laboratory panels from baseline (CBC, CMP)

  Number of patients with changes in CBC or CMP values from baseline CBC or CMP values. Any evidence of thrombocytopenia, anemia, neutropenia, or elevations in white blood counts will require consideration of stopping or pausing infusions by the PI. Slight changes in the ALT, AST, and calcium values are expected due to standard medication uses and will be monitored by PI.

  Baseline, every 4 months post-intervention

• Change in number of participants with changes in radiological parameters

  Number of participants with changes in radiological parameters (xrays and DXA scan) from baseline will be monitored during the study follow up time. DXA scans and x-rays used to assess for any semi-triggers that may require considerations of stopping or pausing infusions.

  Baseline, 8, 20 and 32 months post-intervention

• Change in annualized linear growth velocity

  This study will assess the annualized linear growth velocity at baseline and during cell therapy protocol in children with Type 3 OI (3-10 years of age and pre-pubertal at time of enrollment). Growth charts will be generated using growth measurements obtained every 4 months. Growth charts will be referenced against sex- and age-specific Centers for Disease Control and Prevention (CDC) childhood OI growth reference charts.

  Baseline, every 4 months until 1 year after last infusion intervention

• Change in fracture rate from baseline

  Overt and covert fracture rate will be measured in each child at baseline and at regular intervals during MSC therapy by using a caretaker events diary, limb films, and spine films to tally more objectively new and healing fractures.

  Baseline, every 4 months post-intervention until 1 year after last infusion intervention

• Change in bone mineral density from baseline

  Bone mineral density will be determined by DXA (dual-energy absorptiometry) analysis for TBLH (total body less head), spine and distal radius sites.

  Baseline, yearly until 1 year after last infusion intervention

• Change in bone age

  A bone age assessment is done using left hand radiograph. Bone age will be followed yearly in children of 8 years of age and older at time of enrollment in conjunction with exam and laboratory assessments to determine potential effects of puberty on bone density.

  Baseline, yearly until 1 year after last infusion intervention

• Change in Vertebral Compression Fractures (VCFs)

  Due to abnormal collagen and the associated decrease in BMD, VCFs are common in Type 3 OI. These can be 'silent' and/or associated with back pain. PA TL film and LAT TL film will be obtained to assess VCF's that cannot be assessed by DXA in children. Spine radiographs are within standard of care for treatment of OI.

  Baseline, every 18 months until one year after last infusion intervention

Secondary Outcomes (4)

• Number of participants with changes in bone metabolism markers

  Baseline, every 12 months post-intervention, and at the conclusion of the study (up to 36 months post-intervention)

• Change in Limb Deformity Modified EOS Questionnaire (LD-EOSQ-22) from baseline

  Baseline, annually until 1 year after last infusion

• Change in BAMF (Brief Assessment of Motor Function) from baseline

  Baseline, annually until 1 year after last infusion

• Change in Pediatric Orthopedic Data Collection Instrument (PODCI) from baseline

  Baseline, annually until 1 year after last intervention

Study Arms (1)

Children with OI receiving Bone marrow-derived MSCs infusion

EXPERIMENTAL

Intravenously-infused allogeneic, bone marrow-derived mesenchymal stromal cells (MSCs) in children with Osteogenesis Imperfecta Type III that will be infused at 0 months, 4 months, 8 months, 12 months, 16 months, and 20 months, after enrollment.

Drug: Bone marrow-derived mesenchymal stromal cells (MSCs)

Interventions

Bone marrow-derived mesenchymal stromal cells (MSCs) DRUG

Mesenchymal stromal cells (MSCs) are cells of non-hematopoietic stromal origin that reside in bone marrow and a variety of tissues. MSCs will be prepared in a GMP Cell Production facility and administered to children age 3-10 years (at time of enrollment) with Osteogenesis Imperfecta Type III.

Also known as: MSC infusions

Children with OI receiving Bone marrow-derived MSCs infusion

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \. Parent/legal guardian must be willing to sign consent forms to participate in this trial 2. Participants must be \>3 years of age and \<10 years of age at time of enrollment 3. Must carry mutation in either COL1A1 or COL1A2 genes and based on clinical assessment have severe Type 3 OI\* 4. Must be pre-pubertal to minimize potential influence of hormonal effects on growth velocity and BMD; for children who may be entering puberty at or near upper end of this age bracket, puberty assessment will be based on clinical and laboratory findings 5. Must have received IV pamidronate therapy for at least one year prior to study initiation.
• Type 3 OI will be confirmed with an Invitae Skeletal Dysplasia test, and clinical assessment including:
• Blue/grey sclerae
• Presence of prenatal fractures (on ultrasound when available)
• Deformities present at birth (confirming prenatal fractures)
• Severity of fractures and progressive deformities although no absolute 'number' of fractures is available

You may not qualify if:

• Lacking confirmation of mutation in either COLA1A1 or COL1A2 genes
• Other pathological types of OI
• Any concurrent medical issue(s) known to decrease BMD (e.g., malabsorption conditions, glucocorticoid use)
• Participation in other clinical trial
• Vitamin D deficiency (\<20 ng/dL) despite treatment
• Clinically significant thrombocytopenia as defined by a platelet count of \< 150,000x103/microliter ; anemia as defined by hemoglobin \< 5th percentile for age (\<11.5g/dL); neutropenia as defined by absolute neutrophil count \< 1.5 x103/microliter; or elevations in the white blood cell count as defined by 3-6 year old-WBC \> 15.5WBC x 103/microliter; 6-9 year old WBC \>13.5 x103/microliter (Flerlage 2015)
• \. PRA screening positive for anti-HLA antibodies 9. Elevated LFT's greater than 2 times the upper limit of normal 10. Other genetic disorders 11. Other skeletal dysplasia disorders 12. Other primary or secondary bone disorders 13. History of acute or chronic infections 14. History of cancer 15. History of thrombosis or prothrombotic disorders 16. History of heart disease 17. History of diabetes 18. History of strokes 19. History of vascular conditions 20. History of lung disease

Sponsors & Collaborators

• Emory University: lead

MeSH Terms

Conditions

Osteogenesis Imperfecta; Osteogenesis imperfecta, type 3

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

• Doris Fadoju, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Doris Fadoju, MD

CONTACT

404-712-9839; doris.o.fadoju@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 8, 2022
• First Posted: September 29, 2022
• Study Start: February 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following publication and then for a minimum of 5 years
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to edwin.horwitz@emory.edu. To gain access, data requestor will need to sign a data access agreement.