A Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients

NCT02640807 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CLI-107-15
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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-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.

Conditions

Severe Sepsis With Septic Shock

Keywords

sepsis lymphocytopenia IL-7; immune reconstitution

Outcome Measures

Primary Outcomes (1)

• Immune Reconstitution of Lymphocytopenic Sepsis Patients

  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 Outcomes (2)

• CYT107 Effect on Absolute Lymphocyte Count

  Day 42

• CYT107 Immunogenicity

  Day 60

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 (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

Also known as: CYT107

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 (Sepsis-related organ failure assessment) 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 (ICU may also include a close medical ward on the same study site where the patient will remain under medical control of the Investigator).
• Ability to obtain a signed informed consent from patient or LAR (Legally Authorized Representative) 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

• Revimmune: lead
• Vanderbilt University School of Medicine: collaborator
• Washington University School of Medicine: collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212-1050, United States

Location

Related Publications (12)

• Hotchkiss RS, Moldawer LL. Parallels between cancer and infectious disease. N Engl J Med. 2014 Jul 24;371(4):380-3. doi: 10.1056/NEJMcibr1404664. No abstract available.

  PMID: 25054723 BACKGROUND

• Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available.

  PMID: 12519925 RESULT

• Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD 2nd, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011 Dec 21;306(23):2594-605. doi: 10.1001/jama.2011.1829.

  PMID: 22187279 RESULT

• Hall MW, Knatz NL, Vetterly C, Tomarello S, Wewers MD, Volk HD, Carcillo JA. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med. 2011 Mar;37(3):525-32. doi: 10.1007/s00134-010-2088-x. Epub 2010 Dec 10.

  PMID: 21153402 RESULT

• Hotchkiss RS, Coopersmith CM, McDunn JE, Ferguson TA. The sepsis seesaw: tilting toward immunosuppression. Nat Med. 2009 May;15(5):496-7. doi: 10.1038/nm0509-496.

  PMID: 19424209 RESULT

• Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. 2013 Mar;13(3):260-8. doi: 10.1016/S1473-3099(13)70001-X.

  PMID: 23427891 RESULT

• Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15.

  PMID: 24232462 RESULT

• Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol. 2011 May;11(5):330-42. doi: 10.1038/nri2970.

  PMID: 21508983 RESULT

• Morre M, Beq S. Interleukin-7 and immune reconstitution in cancer patients: a new paradigm for dramatically increasing overall survival. Target Oncol. 2012 Mar;7(1):55-68. doi: 10.1007/s11523-012-0210-4. Epub 2012 Mar 2.

  PMID: 22383042 RESULT

• Unsinger J, Burnham CA, McDonough J, Morre M, Prakash PS, Caldwell CC, Dunne WM Jr, Hotchkiss RS. Interleukin-7 ameliorates immune dysfunction and improves survival in a 2-hit model of fungal sepsis. J Infect Dis. 2012 Aug 15;206(4):606-16. doi: 10.1093/infdis/jis383. Epub 2012 Jun 12.

  PMID: 22693226 RESULT

• Levy Y, Lacabaratz C, Weiss L, Viard JP, Goujard C, Lelievre JD, Boue F, Molina JM, Rouzioux C, Avettand-Fenoel V, Croughs T, Beq S, Thiebaut R, Chene G, Morre M, Delfraissy JF. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009 Apr;119(4):997-1007. doi: 10.1172/JCI38052. Epub 2009 Mar 16.

  PMID: 19287090 RESULT

• 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

Results Point of Contact

• Title: Dr Michel Morre, DVM, Chief Scientific Officer
• Organization: Revimmune

m.morre@revimmune.com

+33(0)603357060

Study Officials

• Edward SHERWOOD, MD, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Richard HOTCHKISS, MD, PhD

  Washington University School of Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2015
• First Posted: December 29, 2015
• Study Start: January 1, 2016
• Primary Completion: August 27, 2018
• Study Completion: August 27, 2018
• Last Updated: July 9, 2020
• Results First Posted: July 9, 2020

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)