Immune Reconstitution of Immunosuppressed Sepsis Patients

NCT02797431 | Terminated Phase 2 DMC

• 1 other identifier: I14037 IRIS-7a
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Severe Sepsis With Septic Shock

Outcome Measures

Primary Outcomes (7)

• White blood count

  Number of patients with absolute lymphocyte counts (Multiply the Lymphocytes percentage above by the total number White Blood Count) increased by more than 50% from baseline at Day 42 Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts

  day 1 to Day 42

• lymphocyte percentage

  Number of patients with absolute lymphocyte counts (Multiply the Lymphocytes percentage above by the total number White Blood Count) increased by more than 50% from baseline at Day 42 Kinetic of immune restoration through weekly measures of Absolute Lymphocyte Counts

  Day 1 to Day 42

• Incidence of treatment-Emergent Adverse Events

  Clinical occurrence of adverse events (AEs) and serious adverse events (SAEs) during the duration of the study period ending day 42, as assessed by DAIDS (2.0)

  Day 1 to Day 42

• Mortality

  Day 60

• Mortality

  Day 190

• Mortality

  Day 180

• Mortality

  Day 360

Secondary Outcomes (9)

• CYT107 Pharmacokinetic Cmax

  Day 1 and Day 22

• CYT107 Pharmacokinetic AUC

  Day 1 and Day 22

• CYT107 Pharmacokinetic half life

  Day 1 and Day 22

• Quantification of positive binding antibodies against CYT107

  Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360

• Specific CYT107 neutralizing antibodies

  Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360

Study Arms (3)

CYT107 high frequency

EXPERIMENTAL

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

Drug: Interleukin-7

CYT107 low frequency

EXPERIMENTAL

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: Interleukin-7; Drug: Placebo

Control

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Interleukin-7 DRUG

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

Also known as: CYT 107

CYT107 high frequency; CYT107 low frequency

Placebo DRUG

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

Also known as: NaCl 0.9%

CYT107 low frequency; Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of age ≥ 18 yrs and older but \< 80 yrs
• Patients with persistent suspected sepsis at 48-120 hrs after admission
• Two or more criteria for the systemic inflammatory response syndrome (SIRS) (see reference #19 for SIRS criteria) and a clinically or microbiologically suspected infection.
• 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
• 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.
• 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.
• Predicted length of stay in the ICU of up to two weeks after starting drug therapy treatment in the trial
• Ability to obtain a signed informed consent from patient or LAR consent.

You may not qualify if:

• Cancer with current chemotherapy or radiotherapy and/or .receipt of chemotherapy or radiotherapy within the last 6 weeks
• 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
• 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.
• Patients who have received solid organ transplant or bone marrow transplant
• Patients with active or a history of acute or chronic lymphocytic leukemia
• AIDS-defining illness (category C) diagnosed within the last 12 months prior to study entry
• History of splenectomy
• Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
• Pregnant or lactating women
• 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.
• 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
• 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
• Prisoners

Sponsors & Collaborators

• University Hospital, Limoges: lead
• Revimmune: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (3)

CHU LIMOGES Service de Réanimation

Limoges, France

Location

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

Lyon, 69003, France

Location

Hopital Lariboisière - Service d'anesthésie-réanimation

Paris, 75010, France

Location

Related Publications (1)

• 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.

  PMID: 29515037 DERIVED

MeSH Terms

Interventions

Interleukin-7; Sodium Chloride

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Bruno FRANCOIS, DM

  University Hospital, Limoges

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: June 13, 2016
• Study Start: January 14, 2016
• Primary Completion: March 21, 2017
• Study Completion: November 13, 2017
• Last Updated: November 29, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)