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Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients (AMETHYST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04961658
Recruitment Status : Recruiting
First Posted : July 14, 2021
Last Update Posted : November 18, 2022
Sponsor:
Information provided by (Responsible Party):
Northern Therapeutics

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.

Condition or disease Intervention/treatment Phase
Septic Shock Biological: GEM00220 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients
Actual Study Start Date : August 11, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Arm Intervention/treatment
Experimental: Treatment Arm - Low Dose
Participants will receive a single dose of GEM00220 at 15 million cells
Biological: GEM00220
Cryopreserved allogeneic, enhanced MSCs administered as a single intravenous infusion

Experimental: Treatment arm - Mid dose
Participants will receive a single dose of GEM00220 at 60 million cells
Biological: GEM00220
Cryopreserved allogeneic, enhanced MSCs administered as a single intravenous infusion

Experimental: Treatment arm - High dose
Participants will receive a single dose of GEM00220 at 150 million cells
Biological: GEM00220
Cryopreserved allogeneic, enhanced MSCs administered as a single intravenous infusion




Primary Outcome Measures :
  1. The safety of GEM00220 will be assessed by monitoring adverse events [ Time Frame: Baseline to 28 days ]
  2. Maximum Feasible Tolerated Dose [ Time Frame: Baseline to 28 days ]
    The highest dose which does not meet any of the pre-defined stopping criteria



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patients age 18 years and older
  2. 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.
  3. 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.
  4. At least 1 other new organ dysfunction defined by the following:

    1. 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)
    2. Respiratory: Need for invasive mechanical ventilation or a P/F ratio < 250
    3. Hematological: Platelets < 100 x10^9/L, or a drop of 50 x10^9/L in the 3 days prior to enrollment
    4. Metabolic Acidosis: Arterial pH < 7.30 in association with base deficit > 5 mmol/L OR a lactate >/= to 3.0 mmol/L

Exclusion Criteria:

  1. Pregnant or lactating
  2. Currently receiving extracorporeal life support
  3. Documented COVID-19 (SARS-CoV2) or influenza infection (confirmed by laboratory testing)
  4. Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the past year
  5. 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
  6. Moderate to severe chronic liver disease (Childs-Pugh Score > 12)
  7. Severe chronic respiratory disease with a baseline PaCO2 > 50 mm Hg or the use of home oxygen
  8. Documented deep venous thrombosis or pulmonary embolism within the past 3 months
  9. Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use >6months)
  10. 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
  11. Concurrent use of immunomodulatory biologic drugs or TNF-α inhibitors
  12. Participation in another interventional study involving an investigational new drug within 30 days prior to enrolment
  13. Moribund patient not expected to survive 24 hours
  14. 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04961658


Contacts
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Contact: Michael Callahan, MD, DTM&H (UK), MSPH 343-291-1197 mvcallahan@mgh.harvard.edu
Contact: Jackie Whyte, MSc 613-859-4849 jwhyte@northernther.com

Locations
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Canada, Ontario
Markham Stouffville Hospital - Oak Valley Health Recruiting
Markham, Ontario, Canada, L3P 7P3
Contact: Valerie Sales, BSc, MD, CM, FRCP(C)       vsales@oakvalleyhealth.ca   
Principal Investigator: Valerie Sales, BSc, MD, CM, FRCP(C)         
Sub-Investigator: Subarna Thirugnanam, BSc Hons., M.D., FRCPC         
Sub-Investigator: Anthony LaDelfa, MD, FRCPC         
Sub-Investigator: Jeya Nadarajah, MD, MSc, FRCPC         
Lakeridge Health Recruiting
Oshawa, Ontario, Canada, L1G 2B9
Contact: Karim Soliman, MD, FRCP         
Principal Investigator: Karim Soliman, MD, FRCP         
Sub-Investigator: Shannon Fernando, MD, MSc, FRCPC         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Claudia dos Santos, MD, MSc, BSc, FRCPC         
Principal Investigator: Claudia dos Santos, MD, MSc, BSc         
Sub-Investigator: Michael Sklar, MD, BSc, FRCPC         
Sponsors and Collaborators
Northern Therapeutics
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Responsible Party: Northern Therapeutics
ClinicalTrials.gov Identifier: NCT04961658    
Other Study ID Numbers: CT-GEM-001
First Posted: July 14, 2021    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Northern Therapeutics:
Sepsis
Bacteria
Septic Shock
Mesenchymal Stromal Cells
Inflammation
Mesenchymal Stem Cells
Infection
Additional relevant MeSH terms:
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Shock, Septic
Shock
Pathologic Processes
Sepsis
Infections
Systemic Inflammatory Response Syndrome
Inflammation