Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Symptomatic COVID-19 Infection Laboratory-Confirmed
Conditions
Brief summary
This phase I/IIa trial studies the best dose and side effects of rintatolimod and interferon (IFN) alpha-2b in treating cancer patients with COVID-19 infection. Interferon alpha is a protein important for defense against viruses. It activates immune responses that help to clear viral infection. Rintatolimod is double stranded ribonucleic acid (RNA) designed to mimic viral infection by stimulating immune pathways that are normally activated during viral infection. Giving rintatolimod and interferon alpha-2b may activate the immune system to limit the replication and spread of the virus.
Detailed description
PRIMARY OBJECTIVES: I. To determine the safety of the combination of intravenous (i.v.) rintatolimod administered with or without i.v. IFN alpha (recombinant interferon alfa-2b \[Intron A\]) in patients with cancer with coronavirus disease 2019 (COVID-19). II. Determine the kinetics of viral load in nasopharyngeal swabs in the course of treatment and Days 7 and 14. SECONDARY OBJECTIVES: I. To assess the efficacy of the treatment combination in patients with cancer with COVID-19. II. Determine the kinetics of viral load in the peripheral blood in the course of treatment and Days 7 and 14. III. Determine the kinetics of changes of the immune subsets and circulating inflammatory mediators (including C-reactive protein \[CRP\], cytokines, chemokines, interferons) in peripheral blood in the course of treatment and Days 7 and 14. IV. Determine the induction of known mediators of antiviral immunity that include (myxovirus resistance gene, MxA; protein Kinase R (PKR); oligoadenylate synthetase-2 (OAS2); RNAse-L, IFN-stimulated gene-15 (ISG15); IFN-induced proteins with tetratricopeptide repeats (IFIT1) and IFN-inducible transmembrane protein 3 (IFITM3), TLR3, RIG-I, MDA5, IRF3, IRF7, in nasopharyngeal swabs material and blood cells of patients on all tiers of treatment. OUTLINE: This is a phase I, dose-escalation study of recombinant interferon alfa-2b followed by a phase II study. LEAD-IN PHASE: Patients receive rintatolimod IV over 2.5-3 hours on day 1 and day 3 (or 4). ARM I: Patients receive rintatolimod IV over 2.5-3 hours and recombinant interferon alfa-2b IV over 20 minutes on day 1 and on day 3 or 4 in the absence of disease progression or unacceptable toxicity. EXPANSION COHORT: ARM III: Patients receive rintatolimod IV over 2.5-3 hours along with standard of care. Patients are followed up at days 7, 14 and 30 after initiation of the study regimen.
Interventions
BIOLOGICALRecombinant Interferon Alfa-2b
Given IV
DRUGRintatolimod
Given IV
Sponsors
Roswell Park Cancer Institute
National Cancer Institute (NCI)
AIM ImmunoTech Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA (MAIN COHORT): * Patients with cancer, with the exception of patients with active acute leukemia and allogeneic hematopoietic stem cell transplant recipients. Patients may be on active therapy or received therapy (e.g., chemotherapy, radiation or surgery) within 7 years. Patients with active cancer who have not yet been treated (e.g. newly diagnosed cancer or early stage myelodysplastic syndrome \[MDS\] or chronic lymphocytic leukemia \[CLL\]) are eligible. Basal cell cancer and carcinoma in situ treated with local excision alone do not qualify for inclusion * Presence of symptomatic infection, defined by fever (temperature \[T\] \>= 38 degrees Celsius \[C\]) OR respiratory symptoms (cough, nasal congestion, or shortness of breath) OR lung infilitrates on chest X-ray or CT imaging. Diagnosis of COVID-19 is based on polymerase chain reaction (PCR) testing of respiratory samples. * Age equal to \>= 18 years or older (children are excluded because COVID-19 typically has a milder course in children, and lack of safety data of this regimen in children) * Platelet \>= 75,000/uL * Hemoglobin \>= 9 g/dL * Hematocrit \>= 27% * Absolute neutrophil count (ANC) \>= 1000/uL * Creatinine clearance \>= 50 mL/min (Cockcroft-Gault Equation-note: plasma creatine instead of serum is used at Roswell Park) * Total bilirubin =\< 2 X institutional upper limit of normal (ULN) * Aspartate transaminase (AST) (plasma) and alanine transferase (ALT) (plasma) =\< 2 X institutional ULN * Plasma amylase and lipase =\< 2 X institutional ULN * In the absence of COVID-19, a life expectancy of 6 months is expected * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure * NOTE: For blood chemistry labs, Roswell Park clinical blood chemistries are performed on plasma unless otherwise indicated * EXPANSION COHORT: Patients with cancer or allogeneic stem cell transplant recipients with and without a cancer diagnosis * Patients with cancer may be on active therapy or received therapy (e.g., chemotherapy, radiation or surgery) within 7 years * Patients with active cancer who have not yet been treated (e.g. newly diagnosed cancer or early stage MDS or CLL) are eligible * Basal cell cancer and carcinoma in situ treated with local excision alone do not qualify for inclusion * Presence of symptomatic infection, defined by fever (T \>= 38.0 degrees C ) OR respiratory symptoms (cough, nasal congestion, or shortness of breath) OR lung infiltrates by chest X-ray or CT imaging. Diagnosis of COVID-19 is based on PCR testing of respiratory samples. Severe infection is excluded * Age equal to \>= 18 years or older (children are excluded because COVID-19 typically has a milder course in children, and lack of safety data of this regimen in children). In the absence of COVID-19, a life expectancy of 6 months is expected * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure. There may be specific instances when the patient can't provide informed consent, e.g. they require mechanical ventilation and are sedated, in which case a health care proxy will be able to provide informed consent. Patients with temporary cognitive impairment will be consented once their capacity has returned. Patients with chronic cognitive impairment, e.g. dementia, that precludes informed consent will not be enrolled.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kinetics of Viral Load | Treatment and days 1, 3/4, 7 and 11 | Will be assessed as cycle threshold values in nasopharyngeal swabs based on quantitative polymerase chain reaction (PCR) in the course of treatment and days 1, 3/4, 7, and 11. |
| Number of Participants With Adverse Events (AEs) | Up to 30 days post treatment initiation, On average, the timeframe is 25 days | This refers to the frequency of grade 3 or 4 AEs considered to be probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version \[v\] 5.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Selected Clinical Efficacy Complications | Up to 30 days post treatment initiation | Will be assessed by the frequency of these complications: (i) progression of infection requiring hospitalization; (ii) respiratory failure requiring mechanical ventilation (primary efficacy endpoint); and (iii) death within 30 days. If present, acute respiratory distress syndrome will be graded by Berlin criteria. |
| Kinetics of Viral Load | Days 1, 3, 7, 14 post treatment initiation | Will be assessed as cycle threshold values in the peripheral blood and nasopharyngeal swab based on quantitative PCR in the course of treatment and days 1, 3, 7, and 14. Data entered are values that were measured, no placeholders were entered, zero is a valid measurement. |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | Days 1, 4 , 7, 14 and 30 post treatment initiation | Gene expresssion measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | Days 1, 4, 7, 14 and 30 post treatment | Gene expression measured by QPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | Days 1, 4, 7, 14, and 30 post treatment | Gene expression measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | Days 1, 4, 7, 14 and 30 post treatment | Gene expression measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | Days 1, 4, 7, and 30 post treatment | Gene expression measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | Days 1, 4, 7, 14 and 30 post treatment | gene expression measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | Days 1, 4, 7, 14 and 30 post treatment | Gene expression measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | Days 1, 4, 7, 14 and 30 post treatment | Gene expression measured by qPCR |
| Known Mediators of Antiviral Immunity (RIG-1) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator RIG-1 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (ISG-15) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator ISG-15 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (RNAseL) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator RNAseL of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (OAS2) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator OAS2 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (ACE2) | Days 1, and 14 post treatment | Induction of known mediator ACE2 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (Mx1) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator Mx1 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (IFIT1) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator IFIT1 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (IFITM3) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator IFITM3 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (IRF3) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator IRF3 of antiviral immunity measured by qPCR |
| Known Mediators of Antiviral Immunity (IRF7) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator IRF7 of antiviral immunity measured by qPCR |
| Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | Days 1, 4, 7, 14 and 30 post treatment | Gene expression measured by qPCR |
| Known Mediators of Antiviral Immunity (TLR-3) | Days 1, 4, 7, 14 and 30 post treatment | Induction of known mediator TLR-3 of antiviral immunity measured by qPCR |
Other
| Measure | Time frame | Description |
|---|---|---|
| Known Mediators of Antiviral Immunity | Up to 30 days post treatment initiation | Will assess the induction of known mediators of antiviral immunity that include (myxovirus resistance gene, MxA; protein Kinase R; oligoadenylate synthetase-2; RNAse-L, IFN-stimulated gene-15 (ISG15); IFN-induced proteins with tetratricopeptide repeats, and IFN-inducible transmembrane protein 3, TLR3, RIG-I, MDA5, IRF3, IRF7, in nasopharyngeal swabs material and blood cells of patients on all tiers of treatment. Will also assess the expression of ACE2 (receptor for severe acute respiratory syndrome coronavirus 2 \[SARS-Cov-2\] entry) and potentially other genes involved in SARS-CoV-2 infection will be tested in nasopharyngeal samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 Dose level 1:Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 0 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Biological/Vaccine: Recombinant Interferon Alfa-2b Given IV
Other Names:
Alfatronol Glucoferon Heberon Alfa IFN alpha-2B Interferon alfa 2b Interferon Alfa-2B Interferon Alpha-2b Intron A recombinant interferon alfa-2b Sch 30500 Urifron Viraferon Drug: Rintatolimod Given IV
Other Names:
Ampligen Atvogen RINTATOLIMOD | 4 |
| 2. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 5 MU/M^2 Dose level 2 :Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 5 MU/M\^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Biological/Vaccine: Recombinant Interferon Alfa-2b Given IV
Other Names:
Alfatronol Glucoferon Heberon Alfa IFN alpha-2B Interferon alfa 2b Interferon Alfa-2B Interferon Alpha-2b Intron A recombinant interferon alfa-2b Sch 30500 Urifron Viraferon Drug: Rintatolimod Given IV
Other Names:
Ampligen Atvogen RINTATOLIMOD | 0 |
| 3. Experimental: Rrintatolimod Plus Standard of Care) Patients receive rintatolimod IV over 2.5-3 hours once plus standard of care.
Drug: Rintatolimod Given IV
Other Names:
Ampligen Atvogen RINTATOLIMOD | 0 |
| 4. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 10 MU/M^2 Dose level 3: Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 10 MU/M\^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Biological/Vaccine: Recombinant Interferon Alfa-2b Given IV
Other Names:
Alfatronol Glucoferon Heberon Alfa IFN alpha-2B Interferon alfa 2b Interferon Alfa-2B Interferon Alpha-2b Intron A recombinant interferon alfa-2b Sch 30500 Urifron Viraferon Drug: Rintatolimod Given IV
Other Names:
Ampligen Atvogen RINTATOLIMOD | 0 |
| 5. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 20 MU/M^2 Dose level 4: Patients receive rintatolimod IV over 2.5-3 hours plus recombinant interferon alfa-2b IV 20 MU/M\^2 over 20 minutes on day 1 and on day 3 (or 4) in the absence of disease progression or unacceptable toxicity.
Biological/Vaccine: Recombinant Interferon Alfa-2b Given IV
Other Names:
Alfatronol Glucoferon Heberon Alfa IFN alpha-2B Interferon alfa 2b Interferon Alfa-2B Interferon Alpha-2b Intron A recombinant interferon alfa-2b Sch 30500 Urifron Viraferon Drug: Rintatolimod Given IV
Other Names:
Ampligen Atvogen RINTATOLIMOD | 0 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 |
|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 6 | 66.3 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 4 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 2 / 4 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Kinetics of Viral Load
Will be assessed as cycle threshold values in nasopharyngeal swabs based on quantitative polymerase chain reaction (PCR) in the course of treatment and days 1, 3/4, 7, and 11.
Time frame: Treatment and days 1, 3/4, 7 and 11
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D1 | 4300100.7 Viral Copy Number / mL | Standard Deviation 5.9 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D3/4 | 190808.2 Viral Copy Number / mL | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D7 | 1974796.7 Viral Copy Number / mL | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D11 | 16.6 Viral Copy Number / mL | — |
Primary
Number of Participants With Adverse Events (AEs)
This refers to the frequency of grade 3 or 4 AEs considered to be probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version \[v\] 5.0).
Time frame: Up to 30 days post treatment initiation, On average, the timeframe is 25 days
Population: All treated and eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Number of Participants With Adverse Events (AEs) | 0 Participants |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D1 Pre | 0.0013 Relative mRNA abundance | Standard Deviation 0.0007 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D1 Post | 0.0001 Relative mRNA abundance | Standard Deviation 0.0001 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D4 Pre | 0.0023 Relative mRNA abundance | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D4 Post | 0.0018 Relative mRNA abundance | Standard Deviation 0.0013 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D7 | 0.0011 Relative mRNA abundance | Standard Deviation 0.0009 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D14 | 0.0043 Relative mRNA abundance | Standard Deviation 0.005 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL22) | D30 | 0.0033 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5)
Gene expression measured by QPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D1 Pre | 23.0 Relative mRNA abundance | Standard Deviation 37.5 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D1 Post | 18.6 Relative mRNA abundance | Standard Deviation 30.5 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D4 Pre | 32.0 Relative mRNA abundance | Standard Deviation 39.6 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D4 Post | 28.9 Relative mRNA abundance | Standard Deviation 17 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D7 | 19.6 Relative mRNA abundance | Standard Deviation 28 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D14 | 57.9 Relative mRNA abundance | Standard Deviation 60 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CCL5) | D30 | 116.7 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2)
Gene expresssion measured by qPCR
Time frame: Days 1, 4 , 7, 14 and 30 post treatment initiation
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D1 Pre | 0.82 Relative mRNA abundance | Standard Deviation 0.65 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D1 Post | 0.68 Relative mRNA abundance | Standard Deviation 0.77 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D4 Pre | 1.14 Relative mRNA abundance | Standard Deviation 0.99 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D4 Post | 1.0 Relative mRNA abundance | Standard Deviation 0.35 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D7 | 4.68 Relative mRNA abundance | Standard Deviation 6.92 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D14 | 1.67 Relative mRNA abundance | Standard Deviation 1.99 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (COX2) | D30 | 4.71 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14, and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D1 Pre | 0.01 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D1 Post | 0.01 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D4 Pre | 0.03 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D4 Post | 0.04 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D7 | 0.04 Relative mRNA abundance | Standard Deviation 0.04 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D14 | 0.03 Relative mRNA abundance | Standard Deviation 0.002 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL10) | D30 | 0.05 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, and 30 post treatment
Population: All treated and eligible patients, participants with data collected at each time point were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D1 Pre | 0.0038 Relative mRNA abundance | Standard Deviation 0.0006 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D1 Post | 2,003.9 Relative mRNA abundance | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D4 Pre | 0.00021 Relative mRNA abundance | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D4 Post | 0.0011 Relative mRNA abundance | Standard Deviation 0.0012 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D7 | 0.0005 Relative mRNA abundance | Standard Deviation 0.0003 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (CXCL12) | D30 | 0.0039 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D1 Pre | 0.005 Relative mRNA abundance | Standard Deviation 0.008 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D1 Post | 0.007 Relative mRNA abundance | Standard Deviation 0.009 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D4 Pre | 0.018 Relative mRNA abundance | Standard Deviation 0.00001 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D4 Post | 0.015 Relative mRNA abundance | Standard Deviation 0.003 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D7 | 0.019 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D14 | 0.019 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IDO1) | D30 | 0.029 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D1 Pre | 0.13 Relative mRNA abundance | Standard Deviation 0.12 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D1 Post | 0.22 Relative mRNA abundance | Standard Deviation 0.27 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D4 Pre | 0.60 Relative mRNA abundance | Standard Deviation 0.65 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D4 Post | 0.68 Relative mRNA abundance | Standard Deviation 0.83 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D7 | 0.42 Relative mRNA abundance | Standard Deviation 0.42 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D14 | 0.82 Relative mRNA abundance | Standard Deviation 0.94 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNa) | D30 | 1.58 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1)
Gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D1 Pre | 0.19 Relative mRNA abundance | Standard Deviation 0.18 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D1 Post | 0.35 Relative mRNA abundance | Standard Deviation 0.48 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D4 Pre | 0.83 Relative mRNA abundance | Standard Deviation 0.96 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D4 Post | 0.85 Relative mRNA abundance | Standard Deviation 1.03 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D7 | 0.50 Relative mRNA abundance | Standard Deviation 0.5 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D14 | 1.30 Relative mRNA abundance | Standard Deviation 1.56 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IFNB1) | D30 | 1.68 Relative mRNA abundance | — |
Secondary
Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10)
gene expression measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D1 Pre | 0.075 Relative mRNA abundance | Standard Deviation 0.069 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D1 Post | 0.055 Relative mRNA abundance | Standard Deviation 0.064 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D4 Pre | 0.059 Relative mRNA abundance | Standard Deviation 0.054 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D4 Post | 0.047 Relative mRNA abundance | Standard Deviation 0.033 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D7 | 0.072 Relative mRNA abundance | Standard Deviation 0.071 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D14 | 0.021 Relative mRNA abundance | Standard Deviation 0.007 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Changes of the Immune Subsets and Circulating Inflammatory Mediators in Peripheral Blood (IL-10) | D30 | 0.014 Relative mRNA abundance | — |
Secondary
Kinetics of Viral Load
Will be assessed as cycle threshold values in the peripheral blood and nasopharyngeal swab based on quantitative PCR in the course of treatment and days 1, 3, 7, and 14. Data entered are values that were measured, no placeholders were entered, zero is a valid measurement.
Time frame: Days 1, 3, 7, 14 post treatment initiation
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D1 | 0.0 Relative mRNA abundance | Standard Deviation 0 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D3 | 0.0 Relative mRNA abundance | — |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D7 | 0.31 Relative mRNA abundance | Standard Deviation 0.43 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Kinetics of Viral Load | C1D14 | 0.0 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (ACE2)
Induction of known mediator ACE2 of antiviral immunity measured by qPCR
Time frame: Days 1, and 14 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ACE2) | D1 Post | 0.00012 Relative mRNA abundance | Standard Deviation 0.00013 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ACE2) | D14 | 0.0004 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (IFIT1)
Induction of known mediator IFIT1 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D1 Pre | 0.99 Relative mRNA abundance | Standard Deviation 0.56 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D1 Post | 1.29 Relative mRNA abundance | Standard Deviation 1.2 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D4 Pre | 1.44 Relative mRNA abundance | Standard Deviation 1.34 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D4 Post | 2.14 Relative mRNA abundance | Standard Deviation 2.15 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D7 | 1.34 Relative mRNA abundance | Standard Deviation 1 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D14 | 2.22 Relative mRNA abundance | Standard Deviation 2.37 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFIT1) | D30 | 3.83 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (IFITM3)
Induction of known mediator IFITM3 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D1 Pre | 17.45 Relative mRNA abundance | Standard Deviation 21.64 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D1 Post | 13.97 Relative mRNA abundance | Standard Deviation 13.93 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D4 Pre | 11.10 Relative mRNA abundance | Standard Deviation 1.77 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D4 Post | 14.55 Relative mRNA abundance | Standard Deviation 1.07 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D7 | 12.48 Relative mRNA abundance | Standard Deviation 4.78 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D14 | 7.11 Relative mRNA abundance | Standard Deviation 0.96 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IFITM3) | D30 | 5.93 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (IRF3)
Induction of known mediator IRF3 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D1 Pre | 2.89 Relative mRNA abundance | Standard Deviation 2.83 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D1 Post | 3.04 Relative mRNA abundance | Standard Deviation 2.49 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D4 Pre | 3.07 Relative mRNA abundance | Standard Deviation 3.33 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D4 Post | 4.14 Relative mRNA abundance | Standard Deviation 4.13 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D7 | 2.23 Relative mRNA abundance | Standard Deviation 2.08 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D14 | 4.26 Relative mRNA abundance | Standard Deviation 4.31 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF3) | D30 | 8.14 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (IRF7)
Induction of known mediator IRF7 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D1 Pre | 0.79 Relative mRNA abundance | Standard Deviation 8.88 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D1 Post | 0.41 Relative mRNA abundance | Standard Deviation 0.51 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D4 Pre | 0.47 Relative mRNA abundance | Standard Deviation 0.45 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D4 Post | 0.79 Relative mRNA abundance | Standard Deviation 0.58 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D7 | 0.54 Relative mRNA abundance | Standard Deviation 0.47 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D14 | 0.49 Relative mRNA abundance | Standard Deviation 0.4 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (IRF7) | D30 | 0.91 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (ISG-15)
Induction of known mediator ISG-15 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D1 Pre | 1.29 Relative mRNA abundance | Standard Deviation 2.26 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D1 Post | 1.49 Relative mRNA abundance | Standard Deviation 2.62 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D4 Pre | 0.02 Relative mRNA abundance | Standard Deviation 0.02 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D4 Post | 0.24 Relative mRNA abundance | Standard Deviation 0.02 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D7 | 0.37 Relative mRNA abundance | Standard Deviation 0.14 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D14 | 0.02 Relative mRNA abundance | Standard Deviation 0.002 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (ISG-15) | D30 | 0.23 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (Mx1)
Induction of known mediator Mx1 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D1 Pre | 2.42 Relative mRNA abundance | Standard Deviation 1.69 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D1 Post | 3.15 Relative mRNA abundance | Standard Deviation 2.81 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D4 Pre | 2.60 Relative mRNA abundance | Standard Deviation 1.65 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D4 Post | 3.88 Relative mRNA abundance | Standard Deviation 1.57 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D7 | 3.13 Relative mRNA abundance | Standard Deviation 1.12 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D14 | 2.42 Relative mRNA abundance | Standard Deviation 1.12 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (Mx1) | D30 | 3.40 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (OAS2)
Induction of known mediator OAS2 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D1 Pre | 1.62 Relative mRNA abundance | Standard Deviation 1.44 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D1 Post | 1.92 Relative mRNA abundance | Standard Deviation 1.79 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D4 Pre | 1.54 Relative mRNA abundance | Standard Deviation 0.82 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D4 Post | 2.94 Relative mRNA abundance | Standard Deviation 1.02 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D7 | 1.98 Relative mRNA abundance | Standard Deviation 1.3 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D14 | 2.30 Relative mRNA abundance | Standard Deviation 0.66 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (OAS2) | D30 | 2.74 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (RIG-1)
Induction of known mediator RIG-1 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D1 Pre | 0.27 Relative mRNA abundance | Standard Deviation 0.22 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D1 Post | 0.47 Relative mRNA abundance | Standard Deviation 0.42 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D4 Pre | 0.50 Relative mRNA abundance | Standard Deviation 0.17 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D4 Post | 0.63 Relative mRNA abundance | Standard Deviation 0.3 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D7 | 0.45 Relative mRNA abundance | Standard Deviation 0.36 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D14 | 0.53 Relative mRNA abundance | Standard Deviation 0.33 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RIG-1) | D30 | 1.16 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (RNAseL)
Induction of known mediator RNAseL of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D4 Post | 0.15 Relative mRNA abundance | Standard Deviation 0.07 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D1 Pre | 0.06 Relative mRNA abundance | Standard Deviation 0.04 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D1 Post | 0.10 Relative mRNA abundance | Standard Deviation 0.06 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D4 Pre | 0.10 Relative mRNA abundance | Standard Deviation 0.07 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D7 | 0.13 Relative mRNA abundance | Standard Deviation 0.08 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D14 | 0.10 Relative mRNA abundance | Standard Deviation 0.08 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (RNAseL) | D30 | 0.28 Relative mRNA abundance | — |
Secondary
Known Mediators of Antiviral Immunity (TLR-3)
Induction of known mediator TLR-3 of antiviral immunity measured by qPCR
Time frame: Days 1, 4, 7, 14 and 30 post treatment
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D1 Pre | 0.01 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D1 Post | 0.02 Relative mRNA abundance | Standard Deviation 0.02 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D4 Pre | 0.02 Relative mRNA abundance | Standard Deviation 0.03 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D4 Post | 0.03 Relative mRNA abundance | Standard Deviation 0.03 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D7 | 0.01 Relative mRNA abundance | Standard Deviation 0.01 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D14 | 0.04 Relative mRNA abundance | Standard Deviation 0.04 |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Known Mediators of Antiviral Immunity (TLR-3) | D30 | 0.06 Relative mRNA abundance | — |
Secondary
Number of Participants With Selected Clinical Efficacy Complications
Will be assessed by the frequency of these complications: (i) progression of infection requiring hospitalization; (ii) respiratory failure requiring mechanical ventilation (primary efficacy endpoint); and (iii) death within 30 days. If present, acute respiratory distress syndrome will be graded by Berlin criteria.
Time frame: Up to 30 days post treatment initiation
Population: All treated and evaluable participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Number of Participants With Selected Clinical Efficacy Complications | Total Number of Participants with complications | 2 Participants |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Number of Participants With Selected Clinical Efficacy Complications | Number of participants that experienced progression of infection requiring hospitalization | 2 Participants |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Number of Participants With Selected Clinical Efficacy Complications | Number of participants experienced failure requiring mechanical ventilation | 1 Participants |
| 1. Experimental: Rintatolimod, Recombinant Interferon Alfa-2b 0 MU/M^2 | Number of Participants With Selected Clinical Efficacy Complications | Number of participants that died within 30 days | 2 Participants |
Other Pre-specified
Known Mediators of Antiviral Immunity
Will assess the induction of known mediators of antiviral immunity that include (myxovirus resistance gene, MxA; protein Kinase R; oligoadenylate synthetase-2; RNAse-L, IFN-stimulated gene-15 (ISG15); IFN-induced proteins with tetratricopeptide repeats, and IFN-inducible transmembrane protein 3, TLR3, RIG-I, MDA5, IRF3, IRF7, in nasopharyngeal swabs material and blood cells of patients on all tiers of treatment. Will also assess the expression of ACE2 (receptor for severe acute respiratory syndrome coronavirus 2 \[SARS-Cov-2\] entry) and potentially other genes involved in SARS-CoV-2 infection will be tested in nasopharyngeal samples.
Time frame: Up to 30 days post treatment initiation
Population: No patients were evaluable.