Recombinant Interleukin-7 (CYT107) to Restore Absolute Lymphocyte Counts in Sepsis Patients

NCT03821038 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: IRIS-7-C&D
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 10

Brief Summary

This phase II randomized study will assess the effect of receiving IV recombinant human IL-7 (CYT107) versus placebo in lymphopenic sepsis patients The aim is to confirm the immune cell reconstitution observed in other studies and other patient populations among which the IRIS-7 A\&B study which was conducted in the same patient population.

Conditions

Sepsis, Severe

Keywords

Sepsis; IL-7; lymphocytopenia

Outcome Measures

Primary Outcomes (1)

• Lymphocyte reconstitution

  Change in absolute lymphocyte count (ALC) of ≥ 50%. If this 50% increase over baseline is reached in the placebo group due to natural immune reconstitution, then the day 29 percent increase of ALC over baseline will be compared between the two groups.

  day 29 versus baseline

Secondary Outcomes (20)

• adverse events

  90 days after study treatment initiation

• Secondary Infections

  within 90 days after treatment initiation

• Days in the ICU

  within 90 days after treatment initiation

• readmissions to the ICU

  within 90 days after treatment initiation

• organ support free days

  within 90 days after treatment initiation

Study Arms (2)

CYT107

EXPERIMENTAL

Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks

Biological: CYT107

Placebo

PLACEBO COMPARATOR

Intravenous (IV) administration of the same volume of NaCl 0.9% twice a week for 3 weeks

Drug: Placebos

Interventions

CYT107 BIOLOGICAL

IV twice a week at 10µg/kg for 3 weeks

Also known as: human recombinant glycosylated Interleukin-7

CYT107

Placebos DRUG

IV twice a week at the same volume for 3 weeks

Also known as: saline solution

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A written, signed informed consent, by the patient or the patient's legally authorized representative
• Participants with an absolute lymphocyte count (ALC) ≤ 900 cells/mm3, at two time points at least twelve hours apart, following diagnosis of vasopressor dependent sepsis and,
• the second time point should not be performed earlier than 48 hours after sepsis diagnosis,
• study drug treatment initiation is required no later than 120 hours (up to 5 days) after the last qualifying ALC ≤ 900 cells/mm3 measure, and
• the average value of the two qualifying ALC counts will serve as a baseline to express the percent increase at day 29, or at hospital discharge.
• Patients in the ICU with onset of vasopressor dependent sepsis defined as hypotension requiring treatment with any vasopressor(s) for at least 6 hours to maintain a systolic pressure ≥ 90 mmHg or a mean arterial pressure ≥65 mmHg AND at least 1 of the 2 organ dysfunction criteria below:
• Acute respiratory failure defined as the need for invasive mechanical ventilation for at least 24 hours to support pulmonary function
• Acute kidney injury defined as creatinine \> 2.0 mg/dL (based on new abnormal result following onset of sepsis) OR urine output \< 0.5 mL/kg/hr for \> 4 hours despite adequate fluid resuscitation. In the presence of pre-existing impairment of renal function (defined as a serum creatinine concentration \>2 times the upper limit of the normal reference range prior to the onset of sepsis), the patient must meet the other organ dysfunction criteria.
• Anticipated hospital duration of up to approx. three weeks after initiating study drug treatment to allow 6 study drug administrations (Days 18 or 19 would be final dose)
• This study permits the re-enrollment of a participant who may have been discontinued as a pre-treatment screen failure and/or prior to study drug treatment.
• Age and reproductive status:
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment
• Women must not be breastfeeding
• Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 (the terminal half-life of CYT107 is up to 2 days) plus 30 days (duration of ovulatory cycle) for a total of 2 months post-treatment completion.
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with CYT107 plus 5 half-lives of CYT107 plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.

You may not qualify if:

• Cancer with current chemotherapy or radiotherapy (receipt of chemotherapy or radiotherapy for cancer within the last 6 weeks). All patients with current, or history of, hematologic malignancy (including, but not limited to, ALL, AML, CLL, CML, etc.) or lymphoma will be excluded, regardless of receipt of recent chemotherapy
• Patients with minimal chance of survival and life expectancy less than 3-5 days as defined by an APACHE II score of ≥ 35 at time of consideration for study eligibility
• Patients with history or current evidence of autoimmune disease including for example: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc.
• Patients who have received a 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
• Known history of chronic HBV infection and not on treatment with HBV nucleoside analogues prior to the current hospitalization or HBV DNA \> 100 IU/mL
• Known history of infection with HCV and currently undergoing treatment for HCV infections or has detectable HCV RNA
• Known history of tuberculosis and currently undergoing treatment for tuberculosis
• History of splenectomy
• Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
• Participation in another investigational interventional study testing a drug or a medical device within the last 3 months prior to study entry
• Patients receiving immunosuppressive drugs, e.g., TNF-alpha inhibitors, for any 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 : IL-2, Interferons α, β and γ, GM-CSF, G-CSF, HIV vaccines, immunosuppressive drugs, hydroxyurea, immunoglobulins, adoptive cell therapy
• Prior exposure to IL 7 or other drugs specifically targeting T cells

Sponsors & Collaborators

• Revimmune: lead
• Washington University School of Medicine: collaborator
• University Hospital, Limoges: collaborator
• Emerald Clinical Inc.: collaborator

Study Sites (10)

University of Florida

Gainesville, Florida, 32610-0108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

CHU Angers

Angers, 49933, France

Location

Hopital HENRI MONDOR

Créteil, 94300, France

Location

CHU Dijon Bourgogne

Dijon, 21000, France

Location

University Hospital of Limoges

Limoges, 87042, France

Location

Hôpital Edouard Herriot

Lyon, 69003, France

Location

Chr Orleans

Orléans, 45067, France

Location

Hopital COCHIN

Paris, 75014, France

Location

Chru Bretonneau

Tours, 37044, France

Location

Related Publications (2)

• 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 BACKGROUND

• Daix T, Mathonnet A, Brakenridge S, Dequin PF, Mira JP, Berbille F, Morre M, Jeannet R, Blood T, Unsinger J, Blood J, Walton A, Moldawer LL, Hotchkiss R, Francois B. Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial. Ann Intensive Care. 2023 Mar 12;13(1):17. doi: 10.1186/s13613-023-01109-w.

  PMID: 36906875 DERIVED

MeSH Terms

Conditions

Sepsis; Lymphopenia

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Richard Hotchkiss, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Bruno François, MD

  Limoges Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Open-label pharmacist will prepare masked syringes for the ICU
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: International, multicenter, randomized, double-blinded placebo- controlled

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 29, 2019
• Study Start: June 1, 2019
• Primary Completion: October 6, 2021
• Study Completion: October 6, 2021
• Last Updated: October 27, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); FR (8)