Advanced Mesenchymal Enhanced Cell THerapY for SepTic Patients

NCT04961658 | Terminated Phase 1 DMC

• 1 other identifier: CT-GEM-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

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.

Conditions

Septic Shock

Keywords

Sepsis; Bacteria; Septic Shock; Mesenchymal Stromal Cells; Inflammation; Mesenchymal Stem Cells; Infection

Outcome Measures

Primary Outcomes (2)

• The safety of GEM00220 will be assessed by monitoring adverse events

  Baseline to 28 days

• Maximum Feasible Tolerated Dose

  The highest dose which does not meet any of the pre-defined stopping criteria

  Baseline to 28 days

Study Arms (4)

Treatment Arm - Dose Cohort 1

EXPERIMENTAL

Participants will receive a single dose of GEM00220 at 15 million cells

Biological: GEM00220

Treatment arm - Dose Cohort 2

EXPERIMENTAL

Participants will receive a single dose of GEM00220 at 60 million cells

Biological: GEM00220

Treatment arm - Dose Cohort 3

EXPERIMENTAL

Participants will receive a single dose of GEM00220 at 150 million cells

Biological: GEM00220

Treatment arm - Dose Cohort 4

EXPERIMENTAL

Participants will receive two doses of GEM00220 at 150 million cells each, seperated by 24 hours

Biological: GEM00220

Interventions

GEM00220 BIOLOGICAL

Cryopreserved allogeneic, enhanced MSCs administered as a single intravenous infusion

Treatment Arm - Dose Cohort 1; Treatment arm - Dose Cohort 2; Treatment arm - Dose Cohort 3; Treatment arm - Dose Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 staff physician.
• 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 or requirement for new renal replacement therapy (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

You may not qualify if:

• Pregnant or lactating
• Currently receiving extracorporeal life support
• Major surgery within this hospitalization and not prophylactically anticoagulated
• Documented history of a hypercoagulable state (eg Factor V Leiden) or heparin-induced thrombocytopenia (HIT)
• Body Mass Index (BMI) \> 35
• Documented COVID-19 (SARS-CoV2) within 30 days
• Documentation of viral lung infection as the primary diagnosis (e.g. influenza infection, respiratory syncytial virus (RSV) infection, or other laboratory-confirmed viral lung infection)
• Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the past year
• Documented 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
• Documented history of moderate to severe chronic liver disease (Childs-Pugh Score \> 12)
• Documented history of peripheral vascular disease with a Rutherford classification greater than Grade I, Category 2: moderate claudication
• Severe chronic respiratory disease with a baseline PaCO2 \> 50 mm Hg or the use of home oxygen
• Documented deep venous thrombosis or pulmonary embolism
• Chronic immunosuppression (any chronic immunotherapy including daily oral steroid use \>6months)
• Documented, 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

Sponsors & Collaborators

• Northern Therapeutics: lead

Study Sites (4)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Markham Stouffville Hospital - Oak Valley Health

Markham, Ontario, L3P 7P3, Canada

Location

Lakeridge Health

Oshawa, Ontario, L1G 2B9, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Inflammation; Infections

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A dose-escalation study evaluating GEM00220 cell therapy in 4 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 9 participants.

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 14, 2021
• Study Start: August 11, 2021
• Primary Completion: August 10, 2023
• Study Completion: January 8, 2024
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)