Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) (HS-ARS)
Primary Purpose
Ionizing Radiation Exposure
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Cell therapy
Sponsored by
About this trial
This is an interventional treatment trial for Ionizing Radiation Exposure
Eligibility Criteria
Inclusion Criteria:
Subject was exposed or suspected to have been exposed to ionizing radiation of
≥1Gy and is at risk of developing HS-ARS, as assessed by the treating physician, based on REMM guidelines (see APPENDIX 1).
- PLX-R18 treatment can be initiated within 4 days of exposure.
- Aged ≥18 years.
- Has provided informed consent. -
Exclusion Criteria:
- Known active malignancy or history of malignancy within 3 years prior to screening except for successfully resected skin basal cell carcinoma or skin squamous cell carcinoma not located at the injection sites.
- Known active uncontrolled infection (e.g. viral, fungal, and/or bacterial)
- Known active infection with Hepatitis A, B, or C.
- Pregnancy.
- Known hypersensitivity to: Allogeneic stromal cells, dimethyl sulfoxid (DMSO), human serum albumin, or bovine products.
- In the opinion of the Investigator the subject is at high risk of developing severe allergic/hypersensitivity reactions and a resuscitation kit including epinephrine is not at hand.
In the opinion of the treating physician, the subject is unsuitable for participating in the study.
-
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
4 million PLX-R18 cells/kg-up to a maximal dose of 400 million
Arm Description
Outcomes
Primary Outcome Measures
Any Adverse Reaction
Secondary Outcome Measures
Recovered with no sequelae
The subject has fully recovered from the AE with no residual effects observable.
Recovered with sequelae
The event resolved but the subject has sequelae, which is a condition following a consequence of a disease
Ongoing AE
AE is still ongoing
Overall survival
Overall survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03797040
Brief Title
Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS)
Acronym
HS-ARS
Official Title
Open-label Phase I Study to Evaluate the Safety of PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2021 (Anticipated)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pluristem Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The objective of the study is to evaluate the safety of intramuscular (IM) administration of PLX-R18 in subjects exposed to ionizing radiation and who are at risk of developing HS-ARS.
Indication:Post-Exposure Prevention (PEP) or treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS) in subjects suspected to have been exposed to ionizing radiation.
Detailed Description
This will be a Phase I, open-label safety study; each subject will receive two administrations of PLX-R18, 4 days apart. Each administration of PLX-R18 will contain 4 million cells/kg (up to a maximal dose of 400 million cells). The first administration should be preferably within 48 hours after suspected exposure and no later than 4 days after suspected exposure. The second administration will be provided 4 days after first administration.
All subjects will be hospitalized for at least 24 hours after each administration of PLX-R18,for close monitoring.In order to minimize risks, subjects will be divided in 3 sequential cohorts:
Cohort 1: 9 subjects, treated as soon as possible Cohort 2: 18 subjects, treated at least 12 hours following the first dose administered to the 9th subject Cohort 3: 33 subjects, treated at least 12 hours following the first dose administered to the 27th subject After the completion of each Cohort, stopping rules will be assessed. All subjects will receive PLX-R18 in addition to recommended care per physician discretion, based on the REMM guidelines (APPENDIX 2).
The study will be comprised of 2 periods:
Main study period - Subjects will be followed-up for 12 months and evaluated at the following time points after the first administration: Day 0 (first administration),Day 1, Day 2, Day 3, Day 4 (second administration), Day 5, Day 14 (2 weeks),Day 21 (3 weeks), Day 28 (4 weeks), Day 49 (7 weeks), Day 63 (9 weeks), Day 119(17 weeks), Day 182 (26 weeks), and Day 364 (52 weeks).Long-term survival follow-up -Week 52 to Week 260: During this period, patients will be followed-up for overall survival at: 104 weeks, 156 weeks, 208 weeks and 260 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ionizing Radiation Exposure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Enrollment
27 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
4 million PLX-R18 cells/kg-up to a maximal dose of 400 million
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Cell therapy
Other Intervention Name(s)
PLX-R18
Intervention Description
PLX-R18: Allogeneic ex vivo expanded placental stromal cells
Primary Outcome Measure Information:
Title
Any Adverse Reaction
Time Frame
From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
Secondary Outcome Measure Information:
Title
Recovered with no sequelae
Description
The subject has fully recovered from the AE with no residual effects observable.
Time Frame
From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
Title
Recovered with sequelae
Description
The event resolved but the subject has sequelae, which is a condition following a consequence of a disease
Time Frame
From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
Title
Ongoing AE
Description
AE is still ongoing
Time Frame
From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
Title
Overall survival
Description
Overall survival
Time Frame
From Week 52 to Week 260 patients will be followed-up for overall survival once a year (every 52 weeks±2 after visit 14)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject was exposed or suspected to have been exposed to ionizing radiation of
≥1Gy and is at risk of developing HS-ARS, as assessed by the treating physician, based on REMM guidelines (see APPENDIX 1).
PLX-R18 treatment can be initiated within 4 days of exposure.
Aged ≥18 years.
Has provided informed consent. -
Exclusion Criteria:
Known active malignancy or history of malignancy within 3 years prior to screening except for successfully resected skin basal cell carcinoma or skin squamous cell carcinoma not located at the injection sites.
Known active uncontrolled infection (e.g. viral, fungal, and/or bacterial)
Known active infection with Hepatitis A, B, or C.
Pregnancy.
Known hypersensitivity to: Allogeneic stromal cells, dimethyl sulfoxid (DMSO), human serum albumin, or bovine products.
In the opinion of the Investigator the subject is at high risk of developing severe allergic/hypersensitivity reactions and a resuscitation kit including epinephrine is not at hand.
In the opinion of the treating physician, the subject is unsuitable for participating in the study.
-
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-label Phase I Study for PEP or Treatment of HS-ARS PLX-R18 for the Post-Exposure Prevention (PEP) or Treatment of Hematopoietic Syndrome of Acute Radiation Syndrome (HS-ARS)
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