Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients (AMETHYST)
Primary Purpose
Septic Shock
Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
GEM00220
Sponsored by
About this trial
This is an interventional treatment trial for Septic Shock focused on measuring Sepsis, Bacteria, Septic Shock, Mesenchymal Stromal Cells, Inflammation, Mesenchymal Stem Cells, Infection
Eligibility Criteria
Inclusion Criteria:
- Adult patients age 18 years and older
- Receipt of appropriate antibiotics for the suspected/confirmed bacterial sepsis as the main diagnosis according to the opinion of the treating critical care staff physician.
- Refractory hypotension documented within 48 hours prior to enrolment that requires the institution and ongoing use of vasopressor agents (phenylephrine, norepinephrine, vasopressin, epinephrine, or dopamine >5 mcg/kg/min) for at least 3 hours within 24 hours prior to infusion, despite adequate fluid resuscitation in the opinion of the qualified investigator.
At least 1 other new organ dysfunction defined by the following:
- Renal: Acute kidney injury with creatinine ≥ 150 µmol/L, or ≥ 1.5x the upper limit of normal or the known baseline creatinine, or < 0.5 ml/kg/hr urine output for 6 hours despite adequate fluid resuscitation (patients on chronic hemodialysis or peritoneal dialysis must meet one of the other organ dysfunction criteria)
- Respiratory: Need for invasive mechanical ventilation or a P/F ratio < 250
- Hematological: Platelets < 100 x10^9/L, or a drop of 50 x10^9/L in the 3 days prior to enrollment
- Metabolic Acidosis: Arterial pH < 7.30 in association with base deficit > 5 mmol/L OR a lactate >/= to 3.0 mmol/L
Exclusion Criteria:
- Pregnant or lactating
- Currently receiving extracorporeal life support
- Documented COVID-19 (SARS-CoV2) or influenza infection (confirmed by laboratory testing)
- Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the past year
- History of severe heart failure with a New York Heart Association Functional Class of III or IV, or severe ischemic heart disease with a Canadian Cardiovascular Society angina class score of III or IV
- Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
- Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
- Documented deep venous thrombosis or pulmonary embolism within the past 3 months
- Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
- Uncontrolled HIV infection or end stage HIV/AIDS with CD4+ T-cell counts <50 cells/mm^3, history of hepatitis B, untreated hepatitis C, or active tuberculosis
- Concurrent use of immunomodulatory biologic drugs or TNF-α inhibitors
- Participation in another interventional study involving an investigational new drug within 30 days prior to enrolment
- Moribund patient not expected to survive 24 hours
- Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
Sites / Locations
- Markham Stouffville Hospital - Oak Valley HealthRecruiting
- Lakeridge HealthRecruiting
- St. Michael's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Treatment Arm - Low Dose
Treatment arm - Mid dose
Treatment arm - High dose
Arm Description
Participants will receive a single dose of GEM00220 at 15 million cells
Participants will receive a single dose of GEM00220 at 60 million cells
Participants will receive a single dose of GEM00220 at 150 million cells
Outcomes
Primary Outcome Measures
The safety of GEM00220 will be assessed by monitoring adverse events
Maximum Feasible Tolerated Dose
The highest dose which does not meet any of the pre-defined stopping criteria
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04961658
Brief Title
Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients
Acronym
AMETHYST
Official Title
Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2021 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northern Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Bacterial sepsis occurs in patients with severe infections. The condition is caused by toxic substances (toxins) released from bacteria and the patient's elevated inflammatory response to those toxins. In preclinical studies, human mesenchymal stromal cells (MSCs) have been proven to modulate host inflammation in infections, including sepsis. The purpose of the Phase I, open label, dose escalation safety trial is to determine whether escalating doses of enhanced MSCs (GEM00220) are safe and well tolerated in patients with septic shock.
Detailed Description
This trial consists of 2 sequential parts using the same trial infrastructure:
Phase 1a: A dose escalating and safety trial with pre-defined stopping rules for safety. Up to 9 participants will receive a single infusion of GEM00220. If no safety issues are identified, we will continue to the Phase 1b trial at the maximum feasible tolerated dose.
Phase 1b: A single-arm, open-label extension of the Phase 1a trial to assess early signs of efficacy (major morbidity and mortality). The Phase 1b trial will enroll up to 12 participants to assess early signals of benefit on mortality and major morbidity in a high risk, high mortality population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Septic Shock
Keywords
Sepsis, Bacteria, Septic Shock, Mesenchymal Stromal Cells, Inflammation, Mesenchymal Stem Cells, Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
A dose-escalation study evaluating GEM00220 cell therapy in 3 cohorts with 3 subjects per cohort. Study will proceed from lower dose to next higher dose if no safety concerns are observed in each cohort. If no safety issues are identified, we will continue to the Phase 1b trial.
Phase 1b: A single-arm, open-label extension of the Phase 1a trial to assess early signs of efficacy (major morbidity and mortality). The Phase 1b trial will enroll up to 12 participants.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm - Low Dose
Arm Type
Experimental
Arm Description
Participants will receive a single dose of GEM00220 at 15 million cells
Arm Title
Treatment arm - Mid dose
Arm Type
Experimental
Arm Description
Participants will receive a single dose of GEM00220 at 60 million cells
Arm Title
Treatment arm - High dose
Arm Type
Experimental
Arm Description
Participants will receive a single dose of GEM00220 at 150 million cells
Intervention Type
Biological
Intervention Name(s)
GEM00220
Intervention Description
Cryopreserved allogeneic, enhanced MSCs administered as a single intravenous infusion
Primary Outcome Measure Information:
Title
The safety of GEM00220 will be assessed by monitoring adverse events
Time Frame
Baseline to 28 days
Title
Maximum Feasible Tolerated Dose
Description
The highest dose which does not meet any of the pre-defined stopping criteria
Time Frame
Baseline to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients age 18 years and older
Receipt of appropriate antibiotics for the suspected/confirmed bacterial sepsis as the main diagnosis according to the opinion of the treating critical care staff physician.
Refractory hypotension documented within 48 hours prior to enrolment that requires the institution and ongoing use of vasopressor agents (phenylephrine, norepinephrine, vasopressin, epinephrine, or dopamine >5 mcg/kg/min) for at least 3 hours within 24 hours prior to infusion, despite adequate fluid resuscitation in the opinion of the qualified investigator.
At least 1 other new organ dysfunction defined by the following:
Renal: Acute kidney injury with creatinine ≥ 150 µmol/L, or ≥ 1.5x the upper limit of normal or the known baseline creatinine, or < 0.5 ml/kg/hr urine output for 6 hours despite adequate fluid resuscitation (patients on chronic hemodialysis or peritoneal dialysis must meet one of the other organ dysfunction criteria)
Respiratory: Need for invasive mechanical ventilation or a P/F ratio < 250
Hematological: Platelets < 100 x10^9/L, or a drop of 50 x10^9/L in the 3 days prior to enrollment
Metabolic Acidosis: Arterial pH < 7.30 in association with base deficit > 5 mmol/L OR a lactate >/= to 3.0 mmol/L
Exclusion Criteria:
Pregnant or lactating
Currently receiving extracorporeal life support
Documented COVID-19 (SARS-CoV2) or influenza infection (confirmed by laboratory testing)
Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the past year
History of severe heart failure with a New York Heart Association Functional Class of III or IV, or severe ischemic heart disease with a Canadian Cardiovascular Society angina class score of III or IV
Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
Documented deep venous thrombosis or pulmonary embolism within the past 3 months
Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
Uncontrolled HIV infection or end stage HIV/AIDS with CD4+ T-cell counts <50 cells/mm^3, history of hepatitis B, untreated hepatitis C, or active tuberculosis
Concurrent use of immunomodulatory biologic drugs or TNF-α inhibitors
Participation in another interventional study involving an investigational new drug within 30 days prior to enrolment
Moribund patient not expected to survive 24 hours
Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Callahan, MD, DTM&H (UK), MSPH
Phone
343-291-1197
Email
mvcallahan@mgh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Jackie Whyte, MSc
Phone
613-859-4849
Email
jwhyte@northernther.com
Facility Information:
Facility Name
Markham Stouffville Hospital - Oak Valley Health
City
Markham
State/Province
Ontario
ZIP/Postal Code
L3P 7P3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valerie Sales, BSc, MD, CM, FRCP(C)
Email
vsales@oakvalleyhealth.ca
First Name & Middle Initial & Last Name & Degree
Valerie Sales, BSc, MD, CM, FRCP(C)
First Name & Middle Initial & Last Name & Degree
Subarna Thirugnanam, BSc Hons., M.D., FRCPC
First Name & Middle Initial & Last Name & Degree
Anthony LaDelfa, MD, FRCPC
First Name & Middle Initial & Last Name & Degree
Jeya Nadarajah, MD, MSc, FRCPC
Facility Name
Lakeridge Health
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
L1G 2B9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karim Soliman, MD, FRCP
First Name & Middle Initial & Last Name & Degree
Karim Soliman, MD, FRCP
First Name & Middle Initial & Last Name & Degree
Shannon Fernando, MD, MSc, FRCPC
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia dos Santos, MD, MSc, BSc, FRCPC
First Name & Middle Initial & Last Name & Degree
Claudia dos Santos, MD, MSc, BSc
First Name & Middle Initial & Last Name & Degree
Michael Sklar, MD, BSc, FRCPC
12. IPD Sharing Statement
Plan to Share IPD
No
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Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients
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