A Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients (IRIS-7-B)

July 8, 2020 updated by: Revimmune

A Multicenter, Randomized, Double-blinded, Placebo-controlled Study of Two Dosing Frequencies of Recombinant Interleukin-7 (CYT107) Treatment to Restore Absolute Lymphocyte Counts in Sepsis Patients.

A multicenter, randomized, double-blinded, placebo-controlled study of two dosing frequencies of recombinant Interleukin-7 (CYT107) treatment to restore absolute lymphocyte counts in sepsis patients; IRIS-7B (Immune Reconstitution of Immunosuppressed Sepsis patients).

A parallel study will be performed in France to allow a common statistical analysis of the primary end points and analysis for the enrolled patient population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Sepsis is the leading cause of death in critically ill patients in most intensive care units in Europe and the US. Recently, evidence has accumulated that sepsis progresses from a state of hyper-inflammation to a state of immunosuppression. This immunosuppressive phase is characterized by increased incidence of secondary infections often with relatively avirulent opportunistic type pathogens. Currently, new therapeutic approaches to sepsis are occurring using immuno-adjuvants that boost host immunity. One of the most promising agents Interleukin-7 is an essential, non-redundant, pluripotent cytokine produced mainly by bone marrow and thymic stromal cells that is required for T-cell survival.In addition to its anti-apoptotic properties, IL-7 induces potent proliferation of naïve and memory T-cells potentially supporting replenishment of the peripheral T-cell pool which is severely depleted during sepsis. These effects were confirmed in clinical trials at the National Cancer Institute and in HIV+ patients.

This clinical study will test the ability of IL-7 to restore the absolute lymphocyte counts in septic patients who have markedly reduced levels of circulating lymphocytes. An effect already confirmed in preclinical models of sepsis.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37212-1050
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients of age ≥ 18 yrs and older but < 80 yrs
  2. Patients with persistent suspected sepsis at 48-120 hrs after admission
  3. Two or more criteria for the systemic inflammatory response syndrome (SIRS) (see reference #19 for SIRS criteria) and a clinically or microbiologically suspected infection.
  4. At least one organ failure as defined by a SOFA (Sepsis-related organ failure assessment) score of ≥2 at any time point during the 48-120 hrs after admission to the ICU
  5. Requirement of vasopressor treatment as follows: i) epinephrine or norepinephrine at ≥ 0.05 µg/kg/min ideal body weight; ii) vasopressin, or iii) dopamine at ≥ 4-5 μg/kg/min ideal body weight, continuously for 4 hrs or more, provided that at least 20 ml/kg of ideal body weight of crystalloid or an equivalent volume of colloid was administered during the 24-hour interval surrounding the start of vasopressor treatment, to maintain systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥ 60 mmHg at any time point during their sepsis course preceding enrollment into the IL-7 study.
  6. Lymphopenia with an absolute lymphocyte count ≤ 900 cells/mm3 at either the day of consent or the day prior to consent during their ICU stay.
  7. Predicted length of stay in the ICU of up to two weeks after starting drug therapy treatment in the trial (ICU may also include a close medical ward on the same study site where the patient will remain under medical control of the Investigator).
  8. Ability to obtain a signed informed consent from patient or LAR (Legally Authorized Representative) consent.

Exclusion Criteria:

  1. Cancer with current chemotherapy or radiotherapy and/or .receipt of chemotherapy or radiotherapy within the last 6 weeks
  2. Cardiopulmonary resuscitation within the previous 4 weeks without objective evidence of full neurologic recovery) or patients who have minimal chance of survival and are not expected to live > 3-5 days as defined by an APACHE II score of ≥ 35 at time of consideration for study eligibility
  3. Patients with a history of or who currently have evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosis, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
  4. Patients who have received solid organ transplant or bone marrow transplant
  5. Patients with active or a history of acute or chronic lymphocytic leukemia
  6. AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
  7. History of splenectomy
  8. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
  9. Pregnant or lactating women
  10. Participation in another investigational interventional study within the last 6 months prior to study entry, with the exception of studies aimed at testing sedation products belonging to standard of care such as Propofol, Dexmedetomidine, Midazolam.
  11. Patients receiving immunosuppressive drugs, e.g., TNF-alpha inhibitors, for rheumatoid arthritis, inflammatory bowel disease or any other reason, or systemic corticosteroids other than hydrocortisone at a dose of 300 mg/day
  12. Patients receiving concurrent immunotherapy or biologic agents including: growth factors, cytokines and interleukins, (other than the study medication); for example IL-2,growth factors, interferons, HIV vaccines, immunosuppressive drugs, hydroxyurea, immunoglobulins, adoptive cell therapy

  13. Prisoners

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CYT107 high frequency
Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks
Drug: Interleukin-7
IM (intra-muscular) administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR (International Normalized Ratio) >2.5 or platelet count < 35,000
Other Names:
  • CYT107
Experimental: CYT107 low frequency
Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for the first week, followed by CYT107 and Placebo once a week for the three following weeks
Drug: Placebo
IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
Other Names:
  • NaCl 0.9%
Drug: Interleukin-7
IM (intra-muscular) administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR (International Normalized Ratio) >2.5 or platelet count < 35,000
Other Names:
  • CYT107
Placebo Comparator: Control
Patients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks
Drug: Placebo
IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
Other Names:
  • NaCl 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune Reconstitution of Lymphocytopenic Sepsis Patients
Time Frame: Day 0 to 42

Number of patients showing an increase of Absolute Lymphocyte Count >50% from baseline at Day 42.

Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts
Day 0 to 42

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CYT107 Effect on Absolute Lymphocyte Count
Time Frame: Day 42
Number of Patients with Absolute Lymphocyte Count > 1.2 at Day 42
Day 42
CYT107 Immunogenicity
Time Frame: Day 60
number of patients with binding or neutralizing antibodies against CYT107 at Day 60
Day 60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Revimmune

Collaborators

Washington University School of Medicine
Vanderbilt University School of Medicine

Investigators

  • Principal Investigator: Edward SHERWOOD, MD, PhD, Vanderbilt University Medical Center
  • Study Director: Richard HOTCHKISS, MD, PhD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

August 27, 2018

Study Completion (Actual)

August 27, 2018

Study Registration Dates

First Submitted

December 14, 2015

First Submitted That Met QC Criteria

December 22, 2015

First Posted (Estimate)

December 29, 2015

Study Record Updates

Last Update Posted (Actual)

July 9, 2020

Last Update Submitted That Met QC Criteria

July 8, 2020

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLI-107-15

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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