Severe Sepsis With Septic ShockPhase 2IRIS-7aNCT02797431
Immune Reconstitution of Immunosuppressed Sepsis Patients
A Phase 2 study testing Interleukin-7 in people with Severe Sepsis With Septic Shock, run by University Hospital, Limoges at 3 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Severe Sepsis With Septic Shock
- What is being tested?
- Interleukin-7
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 3 sitesFrance
- Study dates
- 14 Jan 2016to 13 Nov 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
France3 sites
CHU LIMOGES Service de Réanimation
Limoges
Hospice Civil de Lyon - Hôpital Edouard Herriot - Service de Réanimation Médicale
Lyon, 69003
Hopital Lariboisière - Service d'anesthésie-réanimation
Paris, 75010
About this study
Official title: A Multicenter, Randomized, Double-blinded, Placebo-controlled Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients
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.
Read the detailed description
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
- Severe Sepsis With Septic Shock
- Being tested
- Interleukin-7, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-7Drug
Also called CYT 107
IM administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR>2.5 or platelet count < 35,000
PlaceboDrug
Also called NaCl 0.9%
IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000
| Study group | Role | What they receive |
|---|---|---|
| CYT107 high frequency | Experimental | Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks Receives: 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 Receives: Drug: Interleukin-7; Drug: Placebo |
| Control | Placebo comparator | Patients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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)
Measured: Day 1 to Day 42
Mortality
Measured: Day 60
Mortality
Measured: Day 190
Mortality
Measured: Day 180
Mortality
Measured: Day 360
Secondary outcomes (9)
CYT107 Pharmacokinetic Cmax
CYT107 PK: Measure of Peak plasma concentration "Cmax" at Day 1 and Day 22
Measured: Day 1 and Day 22
CYT107 Pharmacokinetic AUC
CYT107 PK: Measure of Area under plasma concentration versus time curve at day 1 and day 22
Measured: Day 1 and Day 22
CYT107 Pharmacokinetic half life
CYT107 PK: Measure plasma concentration half life at day 1 and day 22
Measured: Day 1 and Day 22
Quantification of positive binding antibodies against CYT107
number of patients with positive binding antibodies against CYT107 at Day 1, Day 11, Day 22, Day 60, Day 180 if Day 60 is positive and Day 360 if Day 180 is positive.
Measured: Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360
Specific CYT107 neutralizing antibodies
Number of patients with CYT107 neutralizing antibodies if positive binding antibodies against CYT107 is detected.
Measured: Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360
Incidence of hospital acquired secondary infections
Incidence of hospital acquired secondary infections at Day 42
Measured: Day 42
SOFA score
SOFA score at Day 0 Day 4, Day 8, Day 15, Day 22, Day 29.
Measured: Day 0 Day 4, Day 8, Day 15, Day 22, Day 29
APACHE II score
APACHE II score at Day 0, Day 4, Day 8, Day 15, Day 22, Day 29.
Measured: Day 0, Day 4, Day 8, Day 15, Day 22, Day 29
CYT107 Pharmacodynamic
CYT107 effects on cell counts:
T-CD4+, T-CD8+, T-CD127+ (IL-7R), monocyte HLA-DR+
Measured: Day 1, Day 8, Day 15, Day 22, Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study start14 Jan 2016
- Primary completion21 Mar 2017
- Study completion13 Nov 2017
Why it stopped: failure of supply of test product
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Sepsis With Septic ShockStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Collaborators
- Revimmune, Vanderbilt University Medical Center
- Responsible party
- Sponsor
- Investigators
- Bruno FRANCOIS, DM, Principal investigator, University Hospital, Limoges
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797431
- Sponsor's protocol ID
- I14037 IRIS-7a
- Acronym
- IRIS-7a
- Status last verified
- Nov 2017
- First submitted
- 24 Feb 2016
- Last updated
- 29 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 29515037
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blinded, Placebo-controlled Study of IL-7 to Restore Absolute Lymphocyte Counts in Sepsis Patients
- ClinicalTrials.gov ID
- NCT02797431
- Acronym / sponsor ID
- IRIS-7a / I14037 IRIS-7a
- Conditions
- Severe Sepsis With Septic Shock
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: failure of supply of test product
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Collaborators
- Revimmune, Vanderbilt University Medical Center
- Study start
- 14 Jan 2016 (actual)
- Primary completion
- 21 Mar 2017 (actual)
- Study completion
- 13 Nov 2017 (actual)
- First posted
- 13 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CYT107 high frequency | Experimental | Drug: Interleukin-7Patients will receive Interleukin-7 (CYT107 liquid solution) at 10µg/kg twice a week for 4 weeks |
| CYT107 low frequency | Experimental | Drug: Interleukin-7, Drug: PlaceboPatients 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 |
| Control | Placebo comparator | Drug: PlaceboPatients will receive Placebo (NaCl 0.9%) twice a week for 4 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interleukin-7Also: CYT 107IM administration of CYT107 recombinant glycosylated human IL-7 (SC administration for patients with INR>2.5 or platelet count < 35,000 | Drug | CYT107 high frequency, CYT107 low frequency |
| PlaceboAlso: NaCl 0.9%IM administration of Placebo (SC administration for patients with INR>2.5 or platelet count < 35,000 | Drug | CYT107 low frequency, Control |
Primary outcome
White blood count
Time frame: day 1 to Day 42
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
lymphocyte percentage
Time frame: Day 1 to Day 42
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
Incidence of treatment-Emergent Adverse Events
Time frame: Day 1 to Day 42
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)
Mortality
Time frame: Day 60
Mortality
Time frame: Day 190
Mortality
Time frame: Day 180
Mortality
Time frame: Day 360
9 secondary outcomes
CYT107 Pharmacokinetic Cmax
Time frame: Day 1 and Day 22
CYT107 Pharmacokinetic AUC
Time frame: Day 1 and Day 22
CYT107 Pharmacokinetic half life
Time frame: Day 1 and Day 22
Quantification of positive binding antibodies against CYT107
Time frame: Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360
Specific CYT107 neutralizing antibodies
Time frame: Day 1, Day 11, Day 22, Day 60, Day 180 and Day 360
Incidence of hospital acquired secondary infections
Time frame: Day 42
SOFA score
Time frame: Day 0 Day 4, Day 8, Day 15, Day 22, Day 29
APACHE II score
Time frame: Day 0, Day 4, Day 8, Day 15, Day 22, Day 29
CYT107 Pharmacodynamic
Time frame: Day 1, Day 8, Day 15, Day 22, Day 29
Results and safety
The study was stopped early (reason given: failure of supply of test product). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2017.
- Derived from this study: PubMed 29515037Francois 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruno FRANCOIS, DM principal investigator
University Hospital, Limoges
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interleukin-7 in people with Severe Sepsis With Septic Shock, run by University Hospital, Limoges at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: failure of supply of test product). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
White blood count (time frame: day 1 to Day 42). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02797431, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2017.