Post-aggressive ImmunosuppressionPhase 2/3INFINITYNCT06694740
Effect of Interferon Gamma as a Treatment for Post-aggressive Immunosuppression in Intensive Care Units, a Randomized Bayesian Double-blind Controlled Trial Versus Placebo
A Phase 2/3 study testing Interferon Gamma 1-b in people with Post-aggressive Immunosuppression and Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial summary
The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-aggressive Immunosuppression, Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6, Adult Under Mechanical Ventilation, and Presenting an mHLA-DR Less Than 8,000AB/C
- What is being tested?
- Interferon Gamma 1-b
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 2 sitesFrance
- Study dates
- 24 Feb 2026to May 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient ≥ 18 years old
- SOFA score for first 24 hours post-admission ≥ 6
- Mechanically ventilated at the time of inclusion (non-invasive ventilation (NIV) and high-flow nasal oxygen excluded)
- mHLA-DR< 8,000 AB/C measured between the 5th and 10th day after admission to the intensive care unit
- Patient affiliated to a social security scheme
- Written consent (relative/trusted person)
Who cannot join
- Patient with estimated life expectancy of less than 3 months
- Patients with a predicted remaining stay in intensive care < 72 hours
- Patient with pre-existing immunosuppression: solid cancer active or in remission for < 5 years, active hemopathy or in remission for < 5 years, systemic disease (including in the absence of specific treatment), solid organ transplant or marrow allograft patient, patient suffering from a HIV infection
- Patients with an expected prolonged duration of mechanical ventilation: comatose or vegetative patients (admission for severe stroke with Glasgow score < 8, patient resuscitated from an arterial stroke,) patients with tracheotomy for ENT problems, patients suffering from muscular disease (e.g. myopathy), patients on long-term mechanical ventilation
- Pregnant or breast-feeding women
- Contraindication of Imukin (hypersensitivity to interferon gamma-1b or known hypersensitivity to related products, such as another interferon)
Show all 10Show fewer
- Patients on immunosuppressive therapy, including long-term corticosteroid therapy (>2.5mg/d prednisone equivalent)
- Patients with severe hepatic or renal insufficiency
- Patient included in another interventional clinical trial
- People under court protection and protected adults
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Dr de Roquetaillade
Paris
Dr de Roquetaillade Charles, MD, 0149958442 ext. +33, charles.de-roquetaillade@aphp.fr
- Recruiting
Pr Dépret
Paris
Pr Dépret François, Professor, 01 42 49 95 70 ext. +33, francois.depret@aphp.fr
About this study
The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).
Read the detailed description
The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).
This immunological adaptation, initially implemented as a host defense mechanism to protect against an overwhelming systemic reaction, can, if prolonged, lead to multiple complications resulting in significant delayed morbidity and mortality. Diagnosis is based on the use of immuno-inflammatory biomarkers, the most widely studied of which is monocyte expression of major histocompatibility complex type II molecules (mHLA-DR).
We have recently confirmed that PAIS can affect all types of patients admitted to the intensive care unit, but mainly occurs in the most severe patients. We also showed that the occurrence of PAIS was strongly associated with the subsequent occurrence of secondary infection and excess mortality.
Currently, there is no treatment with proven efficacy for PAIS, but several drugs have been shown to restore leukocyte function in-vitro. Several teams have reported the use of immunostimulatory molecules in patients with treatment failure, with a good safety profile and encouraging results. We believe that earlier treatment of patients with proven PAIS could improve their clinical outcome.
- Conditions
- Post-aggressive Immunosuppression, Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6, Adult Under Mechanical Ventilation, and Presenting an mHLA-DR Less Than 8,000AB/C
- Being tested
- Interferon Gamma 1-b, Placebo
- Keywords
- Critical care, ICU-acquired immune suppression, HLA-DR, immunity, sepsis
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon Gamma 1-bDrug
interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)
PlaceboDrug
Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections)
| Study group | Role | What they receive |
|---|---|---|
| interferon gamma-1b injection | Experimental | Patients randomized to the experimental arm will receive : Recombinant human interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) |
| Placebo injection | Placebo comparator | Patients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of days alive without mechanical ventilation
number of days alive without mechanical ventilation on day 28 after randomization or on discharge from intensive care if this occurs before the 28th day
Measured: on Day 28 after drug administration
Secondary outcomes (9)
Evaluate the efficacy of IFNy in correcting PAIS-defining biological abnormalities (re-ascension of mHLA-DR above 8,000 AB/C) between patients treated with recombinant interferon gamma 1-b versus placebo
Evolution of mHLA-DR measured at Day 0, Day 1, Day 2, Day 3, Day 7 and Day 28 or at discharge from intensive care if earlier (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo.
Measured: Day 1 to Day 7 and at Day 28 post randomization
Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters between patients treated with recombinant interferon gamma 1-b versus placebo
Evolution of inflammation markers (IL-1, IL-2, IL-6, IL-8, TNFa, etc.) measured in plasma at Day 0, Day 3 and Day 7, or at discharge from intensive care if it occurs before (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: Day 0, Day 3 and at Day 7 post randomization
mortality at Day 28 and Day 90 after randomization
Mortality rate at Day 28 and Day 90 after randomization between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: Day 28 and Day 90 after randomization
incidence of nosocomial infections during intensive care unit stay
The incidence of nosocomial infections during an ICU stay between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: from Day 0 to Day 28 (or the discharge from intensive care)
number of days alive whithout antibiotic
Number of days alive without antibiotic assessed on day 28 after randomization between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: Day 28 after drug administration
length of stay in intensive care between patients
Number of days in intensive care between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: from Day 0 to Day 28 (or the discharge from intensive care)
- Compare organ failure score (SOFA) kinetics between patients treated with recombinant interferon gamma 1-b versus placebo
Kinetics of SOFA score assessed at inclusion and during the 7 days following inclusion between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: From inclusion to Day 7
Evaluate, depending on the randomization arm, the transcriptomic profile of circulating peripheral blood mononuclear cells count between patients treated with recombinant interferon gamma 1-b versus placebo
Evolution of the transcriptomic profile of circulating peripheral blood mononuclear cells (PBMCs) using scRNAseq analysis measured at Day 0, Day 3 and Day 7 or upon discharge from intensive care if this occurs earlier.
Measured: Day 0, Day 3 and Day 7 after randomization
Evaluate, depending on the randomization arm the leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo
Evolution and kenetics of the leucocyte count measured at Day 0, Day 1, Day 2, Day 3, Day 7 and Day 28 or at discharge from intensive care if earlier (Day 0 corresponding to the day of inclusion in the study) between patients treated with recombinant interferon gamma 1-b versus placebo
Measured: Day 0 to Day 7 and at Day 28 post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start24 Feb 2026
- Primary completionMar 2029 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-aggressive ImmunosuppressionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charles De ROQUETAILLADE, MD, Study chair, APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06694740
- Sponsor's protocol ID
- APHP220672
- Other IDs
- 2023-506725-11-00, 2023
- Acronym
- INFINITY
- Status last verified
- Jun 2026
- First submitted
- 12 Nov 2024
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Interferon Gamma as a Treatment for Post-aggressive Immunosuppression in Intensive Care Units, a Randomized Bayesian Double-blind Controlled Trial Versus Placebo
- ClinicalTrials.gov ID
- NCT06694740
- Acronym / sponsor ID
- INFINITY / APHP220672
- Conditions
- Post-aggressive Immunosuppression, Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6, Adult Under Mechanical Ventilation, and Presenting an mHLA-DR Less Than 8,000AB/C
- Keywords
- Critical care, ICU-acquired immune suppression, HLA-DR, immunity, sepsis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 24 Feb 2026 (actual)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 19 Nov 2024 (actual)
- 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.
The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).
Detailed description
The vast majority of serious clinical situations leading to intensive care (septic shock, polytrauma, acute cerebral aggression, major surgery) are characterized by significant systemic inflammation. Recently, the existence of a common immune response pattern to acute aggression has been demonstrated, and with it the existence of a phenomenon known as post-aggressive immunosuppression (PAIS).
This immunological adaptation, initially implemented as a host defense mechanism to protect against an overwhelming systemic reaction, can, if prolonged, lead to multiple complications resulting in significant delayed morbidity and mortality. Diagnosis is based on the use of immuno-inflammatory biomarkers, the most widely studied of which is monocyte expression of major histocompatibility complex type II molecules (mHLA-DR).
We have recently confirmed that PAIS can affect all types of patients admitted to the intensive care unit, but mainly occurs in the most severe patients. We also showed that the occurrence of PAIS was strongly associated with the subsequent occurrence of secondary infection and excess mortality.
Currently, there is no treatment with proven efficacy for PAIS, but several drugs have been shown to restore leukocyte function in-vitro. Several teams have reported the use of immunostimulatory molecules in patients with treatment failure, with a good safety profile and encouraging results. We believe that earlier treatment of patients with proven PAIS could improve their clinical outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| interferon gamma-1b injection | Experimental | –Patients randomized to the experimental arm will receive : Recombinant human interferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) |
| Placebo injection | Placebo comparator | Drug: PlaceboPatients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient ≥ 18 years old
- SOFA score for first 24 hours post-admission ≥ 6
- Mechanically ventilated at the time of inclusion (non-invasive ventilation (NIV) and high-flow nasal oxygen excluded)
- mHLA-DR< 8,000 AB/C measured between the 5th and 10th day after admission to the intensive care unit
- Patient affiliated to a social security scheme
Key exclusion criteria (10 listed)
- Patient with estimated life expectancy of less than 3 months
- Patients with a predicted remaining stay in intensive care < 72 hours
- Patient with pre-existing immunosuppression: solid cancer active or in remission for < 5 years, active hemopathy or in remission for < 5 years, systemic disease (including in the absence of specific treatment), solid organ transplant or marrow allograft patient, patient suffering from a HIV infection
- Patients with an expected prolonged duration of mechanical ventilation: comatose or vegetative patients (admission for severe stroke with Glasgow score < 8, patient resuscitated from an arterial stroke,) patients with tracheotomy for ENT problems, patients suffering from muscular disease (e.g. myopathy), patients on long-term mechanical ventilation
- Pregnant or breast-feeding women
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 |
|---|---|---|
| Interferon Gamma 1-binterferon gamma-1b 2 X 106 IU, injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) | Drug | – |
| PlaceboPatients randomized to the placebo arm will receive saline injectable solution. Subcutaneous injection every 24 hours for 3 consecutive days (3 total injections) | Drug | Placebo injection |
Primary outcome
number of days alive without mechanical ventilation
Time frame: on Day 28 after drug administration
number of days alive without mechanical ventilation on day 28 after randomization or on discharge from intensive care if this occurs before the 28th day
9 secondary outcomes
Evaluate the efficacy of IFNy in correcting PAIS-defining biological abnormalities (re-ascension of mHLA-DR above 8,000 AB/C) between patients treated with recombinant interferon gamma 1-b versus placebo
Time frame: Day 1 to Day 7 and at Day 28 post randomization
Evaluate, depending on the randomization arm, the kinetics of plasma inflammatory parameters between patients treated with recombinant interferon gamma 1-b versus placebo
Time frame: Day 0, Day 3 and at Day 7 post randomization
mortality at Day 28 and Day 90 after randomization
Time frame: Day 28 and Day 90 after randomization
incidence of nosocomial infections during intensive care unit stay
Time frame: from Day 0 to Day 28 (or the discharge from intensive care)
number of days alive whithout antibiotic
Time frame: Day 28 after drug administration
length of stay in intensive care between patients
Time frame: from Day 0 to Day 28 (or the discharge from intensive care)
- Compare organ failure score (SOFA) kinetics between patients treated with recombinant interferon gamma 1-b versus placebo
Time frame: From inclusion to Day 7
Evaluate, depending on the randomization arm, the transcriptomic profile of circulating peripheral blood mononuclear cells count between patients treated with recombinant interferon gamma 1-b versus placebo
Time frame: Day 0, Day 3 and Day 7 after randomization
Evaluate, depending on the randomization arm the leucocyte count between patients treated with recombinant interferon gamma 1-b versus placebo
Time frame: Day 0 to Day 7 and at Day 28 post randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2026.
- Individual participant dataSharing planned: Undecided
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.
Charles De ROQUETAILLADE, MD study chair
APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Interferon Gamma 1-b in people with Post-aggressive Immunosuppression and Adult Patients Admitted to Intensive Care With Initial Severity (SOFA of the First 24 Hours Post-admission ≥ 6, run by Assistance Publique - Hôpitaux de Paris at 2 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 6 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 6 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charles De ROQUETAILLADE, MD (01 49 95 55 68 ext. +33, charles.de-roquetaillade@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of days alive without mechanical ventilation (time frame: on Day 28 after drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jul 2026.