Immune Reconstitution of Immunosuppressed Sepsis Patients

NCT ID: NCT02797431

Last Updated: 2017-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-14

Study Completion Date

2017-11-13

Brief Summary

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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-7A (Immune Reconstitution of Immunosuppressed Sepsis patients).

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

Detailed Description

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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.

Conditions

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Severe Sepsis With Septic Shock

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CYT107 high frequency

Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks

Group Type EXPERIMENTAL

Interleukin-7

Intervention Type DRUG

IM administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR\>2.5 or platelet count \< 35,000

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

Group Type EXPERIMENTAL

Interleukin-7

Intervention Type DRUG

IM administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR\>2.5 or platelet count \< 35,000

Placebo

Intervention Type DRUG

IM administration of Placebo (SC administration for patients with INR\>2.5 or platelet count \< 35,000

Control

Patients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

IM administration of Placebo (SC administration for patients with INR\>2.5 or platelet count \< 35,000

Interventions

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Interleukin-7

IM administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR\>2.5 or platelet count \< 35,000

Intervention Type DRUG

Placebo

IM administration of Placebo (SC administration for patients with INR\>2.5 or platelet count \< 35,000

Intervention Type DRUG

Other Intervention Names

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CYT 107 NaCl 0.9%

Eligibility Criteria

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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 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
8. Ability to obtain a signed informed consent from patient or LAR 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Revimmune

INDUSTRY

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role collaborator

University Hospital, Limoges

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bruno FRANCOIS, DM

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Limoges

Locations

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CHU LIMOGES Service de Réanimation

Limoges, , France

Site Status

Hospice Civil de Lyon - Hôpital Edouard Herriot - Service de Réanimation Médicale

Lyon, , France

Site Status

Hopital Lariboisière - Service d'anesthésie-réanimation

Paris, , France

Site Status

Countries

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France

References

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Francois B, Jeannet R, Daix T, Walton AH, Shotwell MS, Unsinger J, Monneret G, Rimmele T, Blood T, Morre M, Gregoire A, Mayo GA, Blood J, Durum SK, Sherwood ER, Hotchkiss RS. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018 Mar 8;3(5):e98960. doi: 10.1172/jci.insight.98960.

Reference Type DERIVED
PMID: 29515037 (View on PubMed)

Other Identifiers

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I14037 IRIS-7a

Identifier Type: -

Identifier Source: org_study_id