Anti-SARS Cov-2 T Cell Infusions for COVID 19

NCT04401410 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: H-47739 BAT IT
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a dose-finding safety trial followed by a randomized pilot trial comparing administration of SARS-CoV2-specific T cells (SARS-CoVSTs) to standard of care treatment in hospitalized patients with COVID19 who are at high risk of requiring mechanical ventilation. The SARS-CoVSTs lines have been made at Baylor College of Medicine from healthy donors who have made a full recovery from COVID19. These cell lines were frozen for later use and will be thawed and used to treat patients who meet the eligibility criteria.

Conditions

SARS-CoV 2; Viral Infection; COVID 19

Keywords

COVID 19; SARS-CoV 2; Viral infection; Multivirus T cell

Outcome Measures

Primary Outcomes (2)

• Dose Escalation Phase: Rate of Dose Limiting Toxicities by CTCAE 5.0 [14 days post infusion]

  Defined as the proportion of subjects with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment. A dose limiting toxicity is defined as any acute GvHD (\> grade 2), grade ≥3 CRS or ICANS, grade ≥3 hematologic toxicity or grade ≥3 non-hematologic adverse events related to the T cell product within 14 days of the VST infusion and that are not due to pre-existing conditions as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.

  14 days post infusion

• Randomized Trial: Rate of Clinical Response as assessed by the World Health Organization (WHO) Ordinal Scale [7 days post-randomization or hospital discharge]

  Clinical Response rate is defined as the proportion of subjects reporting an increase in 2 or more points on the WHO Ordinal Scale. \[Scored on a scale from 0 to 8; where 0 = Uninfected and 8 =Dead\] or until patient is discharged.

  7 Days post-randomization or at time of hospital discharge

Secondary Outcomes (1)

• Randomized Trial: Rate of Treatment-related adverse events (tAE) by CTCAE 5.0 [14 days post-randomization]

  14 days post-randomization

Study Arms (3)

Dose Finding Phase

EXPERIMENTAL

This phase is designed to evaluate the maximum tolerated dose (MTD) of partially HLA-matched SARS-CoVSTs administered to hospitalized COVID19 patients with high risk of progression to mechanical ventilation. The dose finding phase is a standard 3+3 safety study design. The 3 dose levels are: DL1: 1x10\^7 cells (flat dose) DL2: 2x10\^7 cells (flat dose) DL3: 4x10\^7 cells (flat dose)

Biological: Dose Finding Phase (MTD)

Randomized Pilot - SARS-CoVSTs

EXPERIMENTAL

Partially HLA-matched Virus Specific T cells (VSTs) will be given by intravenous injection.

Biological: Partially HLA-matched SARS-CoVSTs

Randomized Pilot - Routine Care

ACTIVE COMPARATOR

Hospitalized patients with COVID-19 will be treated per current institutional guidelines.

Other: Routine care (no SARS-CoVSTs)

Interventions

Dose Finding Phase (MTD) BIOLOGICAL

Enrollment to the dose escalation phase will be staggered. The first patient enrolled on each of the 3 dose levels (DL1, DL2 and DL3) will have to complete the 14-day toxicity monitoring window prior to enrollment of the next patients. Prior to dose escalation, all patients at a particular dose level should have completed the minimum 14-day toxicity monitoring window before enrolling to a higher dose level.

Dose Finding Phase

Partially HLA-matched SARS-CoVSTs BIOLOGICAL

Infusion of SARS-CoVSTs at the MTD level as determined in the Dose Finding Phase

Randomized Pilot - SARS-CoVSTs

Routine care (no SARS-CoVSTs) OTHER

Patients receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).

Randomized Pilot - Routine Care

Eligibility Criteria

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

You may qualify if:

• SARS-CoV-2 infection confirmed by polymerase chain reaction assay (PCR) from a nasopharyngeal swab or other accepted specimen type. (If testing was performed ≥ 5 days before enrollment, this must be repeated and accept only if positive again). Date of COVID test must be ≤ 5 days prior to infusion.
• Currently hospitalized adult patient (≥ 18 years of age) requiring medical care for COVID19
• Peripheral oxygen saturation (SpO2) ≥ 92% on room air
• Hgb ≥ 7.0 gm/dl
• Negative pregnancy test (if applicable)
• Patient or parent/guardian capable of providing informed consent (may be obtained electronically)
• Evidence of pulmonary infiltrates on chest imaging. Any chest imaging findings which would be consistent with COVID19 would qualify (Eg: ground glass opacities, multifocal infiltrates etc.)
• High risk of requiring mechanical ventilation as defined by at least two of the following:
• Age ≥ 60 years of age
• Age ≥ 75 years of age (counts as meeting two criteria)
• Hypertension (HTN)
• Chronic cardiovascular disease other than HTN (eg: Coronary artery disease, congestive heart failure or cardiomyopathies).
• Diabetes Mellitus
• Obesity (BMI ≥ 30)
• Obesity (BMI ≥ 40, counts as meeting two criteria)

You may not qualify if:

• Chronic obstructive pulmonary disease (COPD)
• Current everyday smoker
• Chronic kidney disease (eGFR \< 30 mL/min/1.73 m2 )
• Bronchial asthma (on active treatment prior to admission, eg. Use of rescue inhalers or inhaled corticosteroids or other treatments to prevent/treat attacks).
• Received Anti-thymocyte globulin (ATG), Campath or other T cell immunosuppressive monoclonal antibodies in the 28 days prior to screening for enrollment
• Requiring mechanical ventilation at time of T cell infusion
• Alanine aminotransferase or aspartate aminotransferase greater than 5 x upper limit of normal
• If previously undergone an allogeneic hematopoietic stem cell transplant and have evidence of active acute GVHD greater than or equal to grade 2
• Uncontrolled relapse of malignancy
• Requiring vasopressors
• Known history of autoimmune disease except prior thyroiditis
• Is not suitable at the discretion of the treating physician
• Patients on greater than 6mg/day of dexamethasone (IV) or equivalent
• Greater than grade 1 CRS per American Society for Transplantation and Cellular Therapy (ASTCT) criteria
• Patients should not be enrolled on any other interventional clinical trials for COVID19. Patients may receive routine care for COVID19 per institutional standards (including antivirals such as remdesivir or other FDA-EUA approved products and thromboprophylaxis).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• AlloVir: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Vasileiou S, Hill L, Kuvalekar M, Workineh AG, Watanabe A, Velazquez Y, Lulla S, Mooney K, Lapteva N, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Eagar TN, Carrum G, Grimes KA, Leen AM, Lulla P. Allogeneic, off-the-shelf, SARS-CoV-2-specific T cells (ALVR109) for the treatment of COVID-19 in high-risk patients. Haematologica. 2023 Jul 1;108(7):1840-1850. doi: 10.3324/haematol.2022.281946.

  PMID: 36373249 DERIVED

MeSH Terms

Conditions

Virus Diseases; COVID-19

Interventions

Maximum Tolerated Dose

Condition Hierarchy (Ancestors)

Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Study Officials

• Premal Lulla

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 26, 2020
• Study Start: November 4, 2020
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

US (1)