Mesenchymal Stem Cells (MSCs) for Steroid Refractory Acute GVHD (SR-aGVHD)

A Phase I Safety Study of Single Dose Allogeneic Bone Marrow Derived MSCs for Steroid Refractory Acute Graft vs. Host Disease

The objective of this clinical study is to demonstrate safety and feasibility of single-dose infusion of Ossium MSCs product (OSSM-001) to treat steroid refractory acute GVHD (SR-aGVHD).

Study Overview

• Status: Withdrawn
• Conditions: GVHD,Acute
• Intervention / Treatment: Biological: OSSM-001

Detailed Description

The dose escalation will be used to establish a maximum tolerated dose, starting from 2M cells/kg. If no safety issues are seen, then MSCs dose maybe escalated to 6M cells/kg, 12M cells/kg and 24M cell/kg based on data review from each cohort. Additional studies will be conducted to establish a dosing regimen and to evaluate the safety and efficacy of OSSM-001 for SR-aGVHD patients.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Minimum 18 years of age who have undergone hematopoietic cell transplantation (HCT), from any donor source donor (including HLA-matched related and unrelated, haploidentical and umbilical cord donors) with any conditioning regimen
2. Clinically diagnosed Grades II to IV acute GVHD as per standard criteria occurring within 100 days of HCT

3. Confirmed diagnosis of steroid refractory aGVHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:

   1. Progressing based on organ assessment after at least 3 days at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGVHD, OR
   2. Failure to achieve at a minimum partial response based on organ assessment after 7 days compared to organ stage at the time of initiation of high-dose systemic corticosteroid +/- CNI for the treatment of Grade II-IV aGVHD, OR
   3. Patients who fail corticosteroid taper defined as fulfilling either one of the following criteria:

   i. Requirement for an increase in the corticosteroid dose to methylprednisolone ≥2 mg/kg/day (or equivalent prednisone dose ≥2.5 mg/kg/day), OR

   ii. Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days.

4. Minimum Karnofsky Performance Level of at least 30 or higher at the time of study entry.

Exclusion Criteria:

1. Has received more than one systemic treatment for steroid refractory aGVHD in addition to steroids.
2. Received stem cell therapy in the past
3. Presence of an active uncontrolled infection including significant bacterial, fungal, viral, or parasitic infection requiring treatment
4. Presence of relapsed primary malignancy, or who have been treated for relapse after the HCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
5. Evidence of pulmonary infiltrate or hemorrhage based on imaging or requiring high flow oxygen via face mask
6. Patients who have had treatment with any other investigational agent, device, or procedure within 30days (or 5 half-lives, whichever is greater) prior to enrollment.
7. Patients who have received more than one HCT
8. Any medical or psychological condition or situation deemed by the Investigators to put the patient at increased risk of complications or non-compliance.
9. Unresolved veno-occlusive disease
10. HLA antibody screen positive for HLA antibodies specific against the MSCs products
11. ALT or AST > 5X of upper limit of normal
12. Serum Bilirubin >2 X of upper limit of normal
13. GFR <50 ml/min
14. SpO2 <94% despite being on continuous supplemental oxygen
15. Patients requiring continuous >4L/minute of supplemental oxygen (irrespective of oxygen saturation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2M cells/kg; Dose level 1. 3 subjects will receive OSSM-001 at 2M cells/kg and followed for 28 days post dose to observe for DLT.	Biological: OSSM-001; Direct IV infusion of OSSM-001
Experimental: 6M cells/kg; Dose level 2. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 6M cells/kg and followed for 28 days post dose to observe for DLT.	Biological: OSSM-001; Direct IV infusion of OSSM-001
Experimental: 12M cells/kg; Dose level 3. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 12M cells/kg and followed for 28 days post dose to observe for DLT.	Biological: OSSM-001; Direct IV infusion of OSSM-001
Experimental: 24M cells/kg; Dose level 4. If no DLTs are observed in the previous dose level, 3 subjects will receive OSSM-001 at 24M cells/kg and followed for 28 days post dose to observe for DLT.	Biological: OSSM-001; Direct IV infusion of OSSM-001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety events	OSSM-001 related safety events	112 days (16 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Determine MTD of OSSM-001	112 days (16 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) from initiation of therapy	OS rate at day 112 post initiation of therapy	112 days (16 weeks)
Overall survival (OS) by baseline GVHD grading	OS rate at day 112 by baseline GVHD grading post initiation of therapy	112 days (16 weeks)
Overall survival (OS) stratified by organ involvement	OS rate at day 112 stratified by organ involvement post initiation of therapy	112 days (16 weeks)
Overall disease relapse	Overall disease relapse by day 112 post initiation of therapy	112 days (16 weeks)
Overall opportunistic infection rate	Overall opportunistic infection rate by day 112 post initiation of therapy	112 days (16 weeks)

Collaborators and Investigators

• Sponsor: Ossium Health, Inc.
• Investigators: Study Director: Sagar Munjal, Ossium Health, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 5, 2023
• Primary Completion (Anticipated): June 10, 2024
• Study Completion (Anticipated): October 14, 2024

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Estimate): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: OSSM-001-006-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No