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

NCT ID: NCT03821038

Last Updated: 2021-10-27

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

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-01

Study Completion Date

2021-10-06

Brief Summary

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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.

Detailed Description

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Lymphopenic sepsis Patients will be randomized 3:1 to receive either:

a) Intravenous (IV) administration of CYT107 at 10 μg/kg twice a week for 3 weeks or b) IV placebo (normal saline).

The effect of CYT107 on Lymphocyte and various T cell populations will be documented with a focus on the first 29 days.

Stopping rules will apply if ALC increases to \>2.5 times the upper limit of normal range.

The IRIS-7C \& D studies will be conducted at multiple sites in France and the United States. All sites will use the same study design and similar study protocol for a common statistical analysis of 40 evaluable participants.

Conditions

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Sepsis, Severe

Keywords

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Sepsis IL-7 lymphocytopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

International, multicenter, randomized, double-blinded placebo- controlled
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Open-label pharmacist will prepare masked syringes for the ICU

Study Groups

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CYT107

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

Group Type EXPERIMENTAL

CYT107

Intervention Type BIOLOGICAL

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

IV twice a week at the same volume for 3 weeks

Interventions

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CYT107

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

Intervention Type BIOLOGICAL

Placebos

IV twice a week at the same volume for 3 weeks

Intervention Type DRUG

Other Intervention Names

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human recombinant glycosylated Interleukin-7 saline solution

Eligibility Criteria

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Inclusion Criteria

1. A written, signed informed consent, by the patient or the patient's legally authorized representative
2. 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,

1. the second time point should not be performed earlier than 48 hours after sepsis diagnosis,
2. 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
3. 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.
3. 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:

1. Acute respiratory failure defined as the need for invasive mechanical ventilation for at least 24 hours to support pulmonary function
2. 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.
4. 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)
5. 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.
6. Age and reproductive status:

1. 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
2. Women must not be breastfeeding
3. 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.
4. 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.
5. Azoospermic males are exempt from contraceptive requirements.
6. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements but still must undergo pregnancy testing.

Exclusion Criteria

1. 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
2. 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
3. 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.
4. Patients who have received a 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. 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
8. Known history of infection with HCV and currently undergoing treatment for HCV infections or has detectable HCV RNA
9. Known history of tuberculosis and currently undergoing treatment for tuberculosis
10. History of splenectomy
11. Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia
12. Participation in another investigational interventional study testing a drug or a medical device within the last 3 months prior to study entry
13. 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
14. 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
15. Prior exposure to IL 7 or other drugs specifically targeting T cells
16. Presence of an advanced directive to withhold or withdraw life-sustaining treatment, DNR order or no CPR order, or comfort measures only order
17. Patients for whom prognosis is poor and source control of septic event is considered unlikely per the clinical and research teams.
18. Patients under guardianship
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role collaborator

University Hospital, Limoges

OTHER

Sponsor Role collaborator

Emerald Clinical Inc.

INDUSTRY

Sponsor Role collaborator

Revimmune

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard Hotchkiss, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Bruno François, MD

Role: PRINCIPAL_INVESTIGATOR

Limoges Hospital

Locations

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University of Florida

Gainesville, Florida, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

CHU Angers

Angers, , France

Site Status

Hopital HENRI MONDOR

Créteil, , France

Site Status

CHU Dijon Bourgogne

Dijon, , France

Site Status

University Hospital of Limoges

Limoges, , France

Site Status

Hôpital Edouard Herriot

Lyon, , France

Site Status

Chr Orleans

Orléans, , France

Site Status

Hopital COCHIN

Paris, , France

Site Status

Chru Bretonneau

Tours, , France

Site Status

Countries

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United States 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 BACKGROUND
PMID: 29515037 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36906875 (View on PubMed)

Other Identifiers

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IRIS-7-C&D

Identifier Type: -

Identifier Source: org_study_id