Primary Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
Interferon-gamma, NI-0501, primary HLH, emapalumab
Brief summary
The purpose of this study is to expand the knowledge on the efficacy and safety of emapalumab (previously known as NI-0501) as a treatment for primary haemophagocytic lymphohistiocytosis (HLH) patients, including on long-term outcomes and quality of life assessments. Emapalumab can be administered as the first-line therapy to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the available standard of care. Emapalumab is to be administered until the start of conditioning for hematopoietic stem cell transplantation (HSCT), with an anticipated duration ranging from a minimum of 4 weeks to approximately 12 weeks and not exceeding 6 months. After treatment completion, patients will continue in the study for long-term follow-up until 1 year after either HSCT or last emapalumab infusion (if HSCT is not performed).
Interventions
DRUGEmapalumab
Emapalumab will be administered by intravenous infusion, twice weekly.
Sponsors
Swedish Orphan Biovitrum
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Primary HLH patients with active disease. * Treatment naïve patients or patients having already received HLH conventional therapy, but having not responded, not achieved a satisfactory response or worsened, or reactivated, or are unable to tolerate current standard of care. * Informed consent signed by the patient or by the patient's legally authorized representative. * Received guidance on contraception. Main
Exclusion criteria
* Diagnosis of secondary HLH consequent to a proven rheumatic, metabolic or neoplastic disease. * Active mycobacteria, Histoplasma capsulatum, Shigella, Salmonella, Campylobacter or Leishmania infections. * Evidence of latent tuberculosis. * Presence of malignancy. * Concomitant disease or malformation severely affecting cardiovascular, pulmonary, central nervous system (CNS), liver, or renal function, that in the opinion of the Investigator may significantly affect the likelihood to respond to treatment and/or the assessment of emapalumab safety and/or efficacy. * History of hypersensitivity or allergy to any component of the study regimen. * Receipt of a BCG vaccine within 12 weeks prior to Screening. * Receipt of a live or attenuated-live (other than BCG) vaccine within 6 weeks prior to Screening. * Pregnant or lactating female patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response at Week 8 or End of Treatment (if Earlier) | Up to Week 8 | The overall response rate (ORR) of patients achieving either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | Up to 18 months | Time to first response at any time during the study. |
| Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Up to 18 months | Incidence of adverse events. SAE = serious adverse event; TEAE = treatment-emergent adverse event |
| Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | To Week 8 or End of treatment if before Week 8. | Number of patients experiencing shifts from baseline in the following relevant laboratory parameters are reported: * Biochemistry: glucose ferritin, C-reactive protein (CRP), liver function (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma glutamyl transferase \[γGT\], lactate dehydrogenase \[LDH\], bilirubin, renal function (albumin, creatinine, urea, urea nitrogen), triglycerides * Complete blood count: basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, large unstained cells, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils band form, neutrophils band form/leukocytes, platelets, erythrocytes, leukocytes * Coagulation tests (activated partial thromboplastin time \[aPTT\], aPTT ratio, prothrombin time, prothrombin international normalized ratio \[INR\]), D-dimer, fibrinogen |
| Number of Patients Who Discontinued Emapalumab Treatment | Up to 6 months | Number of patients who discontinued emapalumab treatment for safety reasons. |
| Overall Survival at End of Study | Up to 18 months | Number of patients surviving to the end of the study. |
| Overall Survival to HSCT | From start of treatment to HSCT or from start of treatment until 1 year after EOT for patient who did not undergo HSCT | Number of patients surviving to HSCT. |
| Overall Survival for Patients Receiving HSCT | Up to 1 year post HSCT | Number of patients surviving post HSCT. |
| Event-free Survival | Up to 1 year post HSCT | Number of patients experiencing event-free survival, the duration of which was defined as time from HSCT to date of (whichever occurs first): death from any cause, graft failure, or HLH reactivation. |
| Overall Response at Start of Conditioning | Up to 6 months | Number of patients achieving either a Complete or Partial Response or HLH Improvement, at start of conditioning (or at last emapalumab infusion if HSCT is not performed). |
| Duration of Response | Up to 18 months | Duration of response, i.e., maintenance of the response achieved at any time during the study (with censoring time at start of conditioning for patients with no event) calculated only for patients showing confirmed overall response. Summarized by number of patients experiencing each category of response duration. |
| Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment | Up to 6 months | Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment. |
| Number of Patients Proceeding to HSCT | Up to 18 months | Number of patients able to proceed to HSCT when deemed indicated. |
| Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Up to 6 months | Assessment of the quality of life using the PedsQL Pediatric Quality of Life Inventory. The PedsQL uses a 100-point scale ranging from 0 to 100 with higher values indicating better quality of life. |
| Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Up to 6 months | Assessment of the quality of life using the BASES questionnaire, which is a validated 38-item questionnaire; a reduced nonvalidated 22-item version of the questionnaire is used in an exploratory nature for the secondary endpoint. Subscale scores were calculated using a 5-point Likert scale from 1 to 5 for all questions. Scores for all questions in each subscale were added up and divided by the number of patients in the analysis population to reach the mean score. Subscale scores were calculated for the following domains: * Physical Discomfort (5 questions, '1' = best response, total range 5-25) * Cooperation/Compliance (5 questions, '1' = best response, total range 5-25) * Mood/Behavior (7 questions, '5' = best response, total range 7-35) * Quality of Interactions (3 questions, '1' = best response, total range 3-15) * Activity/Sleep (2 questions, '5' = best response for patient's activity level and '1' = best response for patient's sleeping, total range 2-10) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Up to 1 year follow up post end of treatment with assessments at first dose of emapalumab, Week 4, Week 8, EOT and following treatment at day 100 and at the 1 year follow up visit, with data presented at study day 21 and EOT/Week 8. | The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs). |
| Serum Concentrations of Emapalumab | Up to Week 8, with data presented at Baseline and EOT/W8 | The serum concentration of emapalumab will be measured as a function of time to determine the emapalumab PK profile. |
| Change in Pharmacodynamic Parameters | Up to 18 months with data presented at Baseline and EOT/W8 | Levels (in ng/L) of total IFNγ (interferon gamma), markers of its neutralization (CXCL9 and CXCL10), and sCD25. |
Countries
Canada, Germany, Italy, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All-treated Analysis Set - Treatment naïve The All-treated analysis set included all patients who received any part of an infusion of study drug. The All-treated analysis set was the primary analysis set for efficacy endpoints and was used for safety and PK/PD endpoints. Details are reported in this arm for patients in the All-treated analysis set who were naïve to HLH treatment. | 16 |
| All-treated Analysis Set - Treatment Experienced The All-treated analysis set included all patients who received any part of an infusion of study drug. The All-treated analysis set was the primary analysis set for efficacy endpoints and was used for safety and PK/PD endpoints. Details are reported in this arm for patients in the All-treated analysis set who have received conventional HLH therapy (as per site standard of care), without having obtained a satisfactory response according to the Investigator or having shown signs of intolerance to previous HLH therapy. | 19 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 7 | 9 |
| Overall Study | Study discontinuation due to other reason | 0 | 1 |
Baseline characteristics
| Characteristic | All-treated Analysis Set - Treatment naïve | All-treated Analysis Set - Treatment Experienced | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 16 Participants | 19 Participants | 35 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Body Surface Area (m^2) | 0.415 m^2 STANDARD_DEVIATION 0.3022 | 0.564 m^2 STANDARD_DEVIATION 0.4141 | 0.497 m^2 STANDARD_DEVIATION 0.3698 |
| Body Weight (kg) | 9.599 kg STANDARD_DEVIATION 10.5915 | 13.946 kg STANDARD_DEVIATION 14.4351 | 11.959 kg STANDARD_DEVIATION 12.8309 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 18 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Height/Length (cm) | 67.02 cm STANDARD_DEVIATION 27.416 | 83.41 cm STANDARD_DEVIATION 37.79 | 75.96 cm STANDARD_DEVIATION 34.003 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) White | 6 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 14 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 16 | 9 / 19 | 16 / 35 |
| other Total, other adverse events | 14 / 16 | 19 / 19 | 35 / 35 |
| serious Total, serious adverse events | 16 / 16 | 16 / 19 | 32 / 35 |
Outcome results
Primary
Overall Response at Week 8 or End of Treatment (if Earlier)
The overall response rate (ORR) of patients achieving either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier).
Time frame: Up to Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All-treated Analysis Set | Overall Response at Week 8 or End of Treatment (if Earlier) | 62.9 Percentage of participants |
| All-treated Analysis Set - Treatment naïve | Overall Response at Week 8 or End of Treatment (if Earlier) | 50.0 Percentage of participants |
| All-treated Analysis Set - Treatment Experienced | Overall Response at Week 8 or End of Treatment (if Earlier) | 73.7 Percentage of participants |
Comparison: The primary efficacy endpoint was analyzed with an exact binomial test to evaluate the null hypothesis that the Overall Response Rate was, at most, 40%. This test was performed at the one sided 0.025 significance level.p-value: 0.005395% CI: [44.9, 78.5]Exact binomial
Comparison: The primary efficacy endpoint was analyzed with an exact binomial test to evaluate the null hypothesis that the Overall Response Rate was, at most, 40%. This test was performed at the one sided 0.025 significance level.p-value: 0.2839Exact binomial
Comparison: The primary efficacy endpoint was analyzed with an exact binomial test to evaluate the null hypothesis that the Overall Response Rate was, at most, 40%. This test was performed at the one sided 0.025 significance level.p-value: 0.0031Exact binomial
Secondary
Duration of Response
Duration of response, i.e., maintenance of the response achieved at any time during the study (with censoring time at start of conditioning for patients with no event) calculated only for patients showing confirmed overall response. Summarized by number of patients experiencing each category of response duration.
Time frame: Up to 18 months
Population: Only patients showing at least one maintained response were included. Duration of response is defined as maintenance of response for at least 4 days, achieved at any time during the study until EOT. Patients who do not achieve at least HLH improvement between the date of first dose and EOT are excluded from the analysis. For both first response and loss of response, persistence for at least 4 days is required, otherwise the next response/loss of response period will be considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All-treated Analysis Set | Duration of Response | 61 days |
| All-treated Analysis Set - Treatment naïve | Duration of Response | 40 days |
| All-treated Analysis Set - Treatment Experienced | Duration of Response | 61 days |
Secondary
Event-free Survival
Number of patients experiencing event-free survival, the duration of which was defined as time from HSCT to date of (whichever occurs first): death from any cause, graft failure, or HLH reactivation.
Time frame: Up to 1 year post HSCT
Population: Analysis population based on the number of patients with HSCT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Event-free Survival | 16 Participants |
| All-treated Analysis Set - Treatment naïve | Event-free Survival | 8 Participants |
| All-treated Analysis Set - Treatment Experienced | Event-free Survival | 8 Participants |
Secondary
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8
Number of patients experiencing shifts from baseline in the following relevant laboratory parameters are reported: * Biochemistry: glucose ferritin, C-reactive protein (CRP), liver function (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], gamma glutamyl transferase \[γGT\], lactate dehydrogenase \[LDH\], bilirubin, renal function (albumin, creatinine, urea, urea nitrogen), triglycerides * Complete blood count: basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, large unstained cells, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils band form, neutrophils band form/leukocytes, platelets, erythrocytes, leukocytes * Coagulation tests (activated partial thromboplastin time \[aPTT\], aPTT ratio, prothrombin time, prothrombin international normalized ratio \[INR\]), D-dimer, fibrinogen
Time frame: To Week 8 or End of treatment if before Week 8.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to low | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: high to within | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: low to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: within to low | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: high to within | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to low | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to low | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: within to high | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: low to within | 9 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: high to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: high to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to within | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: high to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to low | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: high to within | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: within to high | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: low to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: low to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to low | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to low | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: high to within | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: high to within | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: high to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: low to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: within to high | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to within | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: high to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to within | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: high to within | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: low to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to low | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: low to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: high to within | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: low to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: within to low | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to high | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to within | 9 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils/leukocytes: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: low to within | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: within to low | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to low | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: within to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: low to within | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: low to within | 8 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils/leukocytes: within to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to low | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: low to within | 9 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: within to low | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: high to within | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to within | 9 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: low to within | 6 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to low | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to high | 2 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: within to low | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: within to high | 3 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to within | 5 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Large unstained cells: high to within | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to low | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: low to within | 4 Participants |
| All-treated Analysis Set | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to within | 13 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to low | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: low to within | 4 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: within to low | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to within | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: low to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: within to low | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: high to within | 6 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: high to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: high to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to low | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: low to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: low to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils/leukocytes: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: low to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: within to low | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to within | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Large unstained cells: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: low to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to low | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to low | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: high to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: low to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: within to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: high to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: within to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: high to within | 4 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: low to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: within to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: high to within | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: within to high | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: low to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: low to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to high | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: high to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: low to within | 4 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: low to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: within to low | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: low to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to low | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: high to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: low to within | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to low | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: high to within | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: high to within | 4 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to within | 6 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: high to within | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: within to high | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: high to within | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: within to high | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to low | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Large unstained cells: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: within to high | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: within to low | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: low to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hemoglobin: low to within | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | D-dimer: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to low | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: within to low | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alanine aminotransferase: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Hematocrit: low to within | 5 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: high to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Platelets: high to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils/leukocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to within | 7 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: within to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: high to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: low to within | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Eosinophils: low to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: within to low | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to low | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils/leukocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: low to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Erythrocytes: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: within to low | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to within | 7 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: low to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Basophils: low to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to low | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: within to low | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Alkaline phosphatase: low to within | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Leukocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: within to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: low to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea nitrogen: low to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to low | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: high to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Ferritin: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: high to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Albumin: low to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | C-reactive protein: within to high | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT: high to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | γGT: high to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: high to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Urea: within to low | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: within to low | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Fibrinogen: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Glucose: high to within | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Creatinine: low to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: low to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: low to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Triglycerides: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: within to low | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lactate dehydrogenase: high to within | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to high | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to low | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes: low to within | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin INR: high to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Monocytes/leukocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to low | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: low to within | 6 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes/leukocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Bilirubin: within to high | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to low | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Prothrombin time: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: within to high | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to high | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | aPTT ratio: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form: high to within | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: within to low | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: within to high | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: low to within | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Lymphocytes: low to within | 2 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Aspartate aminotransferase: high to low | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 | Neutrophils band form/leukocytes: within to low | 0 Participants |
Secondary
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious)
Incidence of adverse events. SAE = serious adverse event; TEAE = treatment-emergent adverse event
Time frame: Up to 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infections | 29 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate TEAEs | 27 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infusion-related reactions | 7 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Treatment-emergent SAEs related to study drug | 4 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs leading to discontinuation of study drug | 7 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe infections | 16 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with an outcome of death | 16 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs | 35 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe TEAEs | 31 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate infections | 15 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs related to study drug | 9 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Serious TEAEs | 32 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild infections | 21 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild TEAEs | 30 Participants |
| All-treated Analysis Set | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Non-TEAEs | 15 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild infections | 10 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Non-TEAEs | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs | 16 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs related to study drug | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild TEAEs | 12 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe TEAEs | 15 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs leading to discontinuation of study drug | 3 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with an outcome of death | 7 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Serious TEAEs | 16 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Treatment-emergent SAEs related to study drug | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infections | 14 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate TEAEs | 12 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate infections | 8 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe infections | 7 Participants |
| All-treated Analysis Set - Treatment naïve | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infusion-related reactions | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild TEAEs | 18 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infusion-related reactions | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with infections | 15 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs related to study drug | 6 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe infections | 9 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Mild infections | 11 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs | 19 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs leading to discontinuation of study drug | 4 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate TEAEs | 15 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | TEAEs with an outcome of death | 9 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Moderate infections | 7 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Serious TEAEs | 16 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Severe TEAEs | 16 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Non-TEAEs | 10 Participants |
| All-treated Analysis Set - Treatment Experienced | Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) | Treatment-emergent SAEs related to study drug | 2 Participants |
Secondary
Number of Patients Proceeding to HSCT
Number of patients able to proceed to HSCT when deemed indicated.
Time frame: Up to 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Number of Patients Proceeding to HSCT | 23 Participants |
| All-treated Analysis Set - Treatment naïve | Number of Patients Proceeding to HSCT | 11 Participants |
| All-treated Analysis Set - Treatment Experienced | Number of Patients Proceeding to HSCT | 12 Participants |
Secondary
Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment
Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.
Time frame: Up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment | 15 Participants |
| All-treated Analysis Set - Treatment naïve | Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment | 8 Participants |
| All-treated Analysis Set - Treatment Experienced | Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment | 7 Participants |
Secondary
Number of Patients Who Discontinued Emapalumab Treatment
Number of patients who discontinued emapalumab treatment for safety reasons.
Time frame: Up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Number of Patients Who Discontinued Emapalumab Treatment | 7 Participants |
| All-treated Analysis Set - Treatment naïve | Number of Patients Who Discontinued Emapalumab Treatment | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Number of Patients Who Discontinued Emapalumab Treatment | 4 Participants |
Secondary
Overall Response at Start of Conditioning
Number of patients achieving either a Complete or Partial Response or HLH Improvement, at start of conditioning (or at last emapalumab infusion if HSCT is not performed).
Time frame: Up to 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All-treated Analysis Set | Overall Response at Start of Conditioning | HLH improvement | 1 Participants |
| All-treated Analysis Set | Overall Response at Start of Conditioning | Complete response | 4 Participants |
| All-treated Analysis Set | Overall Response at Start of Conditioning | Partial response | 11 Participants |
| All-treated Analysis Set | Overall Response at Start of Conditioning | No response | 19 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Response at Start of Conditioning | No response | 8 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Response at Start of Conditioning | HLH improvement | 0 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Response at Start of Conditioning | Partial response | 5 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Response at Start of Conditioning | Complete response | 3 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Response at Start of Conditioning | No response | 11 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Response at Start of Conditioning | Complete response | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Response at Start of Conditioning | HLH improvement | 1 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Response at Start of Conditioning | Partial response | 6 Participants |
Secondary
Overall Survival at End of Study
Number of patients surviving to the end of the study.
Time frame: Up to 18 months
Population: 'All-treated analysis set - treatment experienced' includes a censored observation for 1 patient who discontinued the study early.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All-treated Analysis Set | Overall Survival at End of Study | Alive at end of study | 19 Participants |
| All-treated Analysis Set | Overall Survival at End of Study | Early discontinuation | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Survival at End of Study | Alive at end of study | 9 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Survival at End of Study | Early discontinuation | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Survival at End of Study | Alive at end of study | 10 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Survival at End of Study | Early discontinuation | 1 Participants |
Secondary
Overall Survival for Patients Receiving HSCT
Number of patients surviving post HSCT.
Time frame: Up to 1 year post HSCT
Population: All-treated analysis includes total number or patients who received HSCT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Overall Survival for Patients Receiving HSCT | 17 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Survival for Patients Receiving HSCT | 8 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Survival for Patients Receiving HSCT | 9 Participants |
Secondary
Overall Survival to HSCT
Number of patients surviving to HSCT.
Time frame: From start of treatment to HSCT or from start of treatment until 1 year after EOT for patient who did not undergo HSCT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All-treated Analysis Set | Overall Survival to HSCT | 25 Participants |
| All-treated Analysis Set - Treatment naïve | Overall Survival to HSCT | 12 Participants |
| All-treated Analysis Set - Treatment Experienced | Overall Survival to HSCT | 13 Participants |
Secondary
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES)
Assessment of the quality of life using the BASES questionnaire, which is a validated 38-item questionnaire; a reduced nonvalidated 22-item version of the questionnaire is used in an exploratory nature for the secondary endpoint. Subscale scores were calculated using a 5-point Likert scale from 1 to 5 for all questions. Scores for all questions in each subscale were added up and divided by the number of patients in the analysis population to reach the mean score. Subscale scores were calculated for the following domains: * Physical Discomfort (5 questions, '1' = best response, total range 5-25) * Cooperation/Compliance (5 questions, '1' = best response, total range 5-25) * Mood/Behavior (7 questions, '5' = best response, total range 7-35) * Quality of Interactions (3 questions, '1' = best response, total range 3-15) * Activity/Sleep (2 questions, '5' = best response for patient's activity level and '1' = best response for patient's sleeping, total range 2-10)
Time frame: Up to 6 months
Population: Assessment completed at the end of treatment for those who proceeded/were planned to proceed to HSCT.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Cooperation/compliance | 9.3 scale on a score | Standard Deviation 3.02 |
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Sleep | 2.1 scale on a score | Standard Deviation 1.04 |
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Physical discomfort | 10.0 scale on a score | Standard Deviation 3.57 |
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Mood/behavior | 20.4 scale on a score | Standard Deviation 8.82 |
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Quality of interactions | 5.8 scale on a score | Standard Deviation 2.34 |
| All-treated Analysis Set | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Activity | 3.1 scale on a score | Standard Deviation 1.22 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Quality of interactions | 6.1 scale on a score | Standard Deviation 2.48 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Activity | 2.7 scale on a score | Standard Deviation 0.95 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Cooperation/compliance | 9.6 scale on a score | Standard Deviation 2.76 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Mood/behavior | 15.1 scale on a score | Standard Deviation 8.88 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Sleep | 1.8 scale on a score | Standard Deviation 1.1 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Physical discomfort | 9.4 scale on a score | Standard Deviation 2.99 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Sleep | 2.3 scale on a score | Standard Deviation 1.03 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Cooperation/compliance | 9.1 scale on a score | Standard Deviation 3.4 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Mood/behavior | 25.0 scale on a score | Standard Deviation 6.02 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Quality of interactions | 5.5 scale on a score | Standard Deviation 2.33 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Activity | 3.4 scale on a score | Standard Deviation 1.41 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) | Physical discomfort | 10.5 scale on a score | Standard Deviation 4.14 |
Secondary
Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™
Assessment of the quality of life using the PedsQL Pediatric Quality of Life Inventory. The PedsQL uses a 100-point scale ranging from 0 to 100 with higher values indicating better quality of life.
Time frame: Up to 6 months
Population: Results from the PedsQL were not available for all patients; in addition, due to the age and treatment history of patients, not all age categories were represented in each of the analysis sets.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All-treated Analysis Set | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 1-12 months | 0.208 scale on a score | Standard Deviation 18.0737 |
| All-treated Analysis Set | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 13-24 months | 0.794 scale on a score | Standard Deviation 4.8152 |
| All-treated Analysis Set | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 2-4 years | 8.469 scale on a score | Standard Deviation 9.6897 |
| All-treated Analysis Set | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 8-12 years | 15.978 scale on a score | — |
| All-treated Analysis Set | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 13-18 years | -7.862 scale on a score | Standard Deviation 13.476 |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 8-12 years | 15.978 scale on a score | — |
| All-treated Analysis Set - Treatment naïve | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 1-12 months | -6.514 scale on a score | Standard Deviation 14.8977 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 2-4 years | 8.469 scale on a score | Standard Deviation 9.6897 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 1-12 months | 5.810 scale on a score | Standard Deviation 19.822 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 13-18 years | -7.862 scale on a score | Standard Deviation 13.476 |
| All-treated Analysis Set - Treatment Experienced | Quality of Life Assessed Through PedsQL™, Pediatric Quality of Life Inventory™ | Change from Baseline at EOT/Week 8 - 13-24 months | 0.794 scale on a score | Standard Deviation 4.8152 |
Secondary
Time to Response
Time to first response at any time during the study.
Time frame: Up to 18 months
Population: Only patients with a response were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All-treated Analysis Set | Time to Response | 4 days |
| All-treated Analysis Set - Treatment naïve | Time to Response | 5 days |
| All-treated Analysis Set - Treatment Experienced | Time to Response | 4 days |
Other Pre-specified
Change in Pharmacodynamic Parameters
Levels (in ng/L) of total IFNγ (interferon gamma), markers of its neutralization (CXCL9 and CXCL10), and sCD25.
Time frame: Up to 18 months with data presented at Baseline and EOT/W8
Population: The number of participants analyzed at each timepoint reflects the number of participants who provided samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | Total IFNγ at baseline | 1112.681 ng/L | Standard Deviation 2393.9753 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | Total IFNγ at EOT/Week 8 | 25708.836 ng/L | Standard Deviation 41775.889 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | CXCL10 at baseline | 14195.394 ng/L | Standard Deviation 37588.5073 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | CXCL10 at EOT/Week 8 | 3203.194 ng/L | Standard Deviation 13239.6238 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | CXCL9 at baseline | 14113.999 ng/L | Standard Deviation 34451.6041 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | CXCL9 at EOT/Week 8 | 2109.078 ng/L | Standard Deviation 10100.8802 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | sCD25 at baseline | 17026.171 ng/L | Standard Deviation 13537.8951 |
| All-treated Analysis Set | Change in Pharmacodynamic Parameters | sCD25 at EOT/Week 8 | 9882.585 ng/L | Standard Deviation 8542.0418 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | CXCL10 at baseline | 28501.304 ng/L | Standard Deviation 54928.0152 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | sCD25 at baseline | 23980.603 ng/L | Standard Deviation 13267.5834 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | CXCL10 at EOT/Week 8 | 6355.428 ng/L | Standard Deviation 20287.7247 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | CXCL9 at baseline | 26695.379 ng/L | Standard Deviation 49400.509 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | CXCL9 at EOT/Week 8 | 4749.055 ng/L | Standard Deviation 15555.8338 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | Total IFNγ at baseline | 1356.191 ng/L | Standard Deviation 2550.8868 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | Total IFNγ at EOT/Week 8 | 39233.258 ng/L | Standard Deviation 60957.7563 |
| All-treated Analysis Set - Treatment naïve | Change in Pharmacodynamic Parameters | sCD25 at EOT/Week 8 | 11301.162 ng/L | Standard Deviation 8847.8 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | CXCL10 at baseline | 3654.197 ng/L | Standard Deviation 7505.8959 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | Total IFNγ at EOT/Week 8 | 15941.198 ng/L | Standard Deviation 14695.7764 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | Total IFNγ at baseline | 920.436 ng/L | Standard Deviation 2314.6502 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | CXCL10 at EOT/Week 8 | 926.580 ng/L | Standard Deviation 2389.4231 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | sCD25 at baseline | 11535.830 ng/L | Standard Deviation 11268.1072 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | CXCL9 at EOT/Week 8 | 202.428 ng/L | Standard Deviation 240.955 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | CXCL9 at baseline | 4181.331 ng/L | Standard Deviation 6470.0963 |
| All-treated Analysis Set - Treatment Experienced | Change in Pharmacodynamic Parameters | sCD25 at EOT/Week 8 | 8858.058 ng/L | Standard Deviation 8417.5485 |
Other Pre-specified
Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
Time frame: Up to 1 year follow up post end of treatment with assessments at first dose of emapalumab, Week 4, Week 8, EOT and following treatment at day 100 and at the 1 year follow up visit, with data presented at study day 21 and EOT/Week 8.
Population: Number of patients who demonstrated a presence of circulating antibodies shown only for visits where a positive result was recorded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All-treated Analysis Set | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at Study Day 21 | 2 Participants |
| All-treated Analysis Set | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at End of Treatment/Week 8 | 1 Participants |
| All-treated Analysis Set - Treatment naïve | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at Study Day 21 | 2 Participants |
| All-treated Analysis Set - Treatment naïve | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at End of Treatment/Week 8 | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at Study Day 21 | 0 Participants |
| All-treated Analysis Set - Treatment Experienced | Number of Patients Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity | Presence of circulating antibodies at End of Treatment/Week 8 | 1 Participants |
Other Pre-specified
Serum Concentrations of Emapalumab
The serum concentration of emapalumab will be measured as a function of time to determine the emapalumab PK profile.
Time frame: Up to Week 8, with data presented at Baseline and EOT/W8
Population: The number of participants analyzed at each timepoint reflects the number of participants who provided samples.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All-treated Analysis Set | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 pre-dose | 258337.456 ng/mL | Standard Deviation 231412.7632 |
| All-treated Analysis Set | Serum Concentrations of Emapalumab | Emapalumab serum concentration at Baseline pre-dose | 14.311 ng/mL | Standard Deviation 50.2717 |
| All-treated Analysis Set | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 post-dose | 142338.620 ng/mL | Standard Deviation 89464.1682 |
| All-treated Analysis Set - Treatment naïve | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 pre-dose | 295521.381 ng/mL | Standard Deviation 296009.6195 |
| All-treated Analysis Set - Treatment naïve | Serum Concentrations of Emapalumab | Emapalumab serum concentration at Baseline pre-dose | 12.899 ng/mL | Standard Deviation 49.9589 |
| All-treated Analysis Set - Treatment naïve | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 post-dose | 205599.340 ng/mL | — |
| All-treated Analysis Set - Treatment Experienced | Serum Concentrations of Emapalumab | Emapalumab serum concentration at Baseline pre-dose | 15.425 ng/mL | Standard Deviation 51.8562 |
| All-treated Analysis Set - Treatment Experienced | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 post-dose | 79077.900 ng/mL | — |
| All-treated Analysis Set - Treatment Experienced | Serum Concentrations of Emapalumab | Emapalumab serum concentration at EOT/Week 8 pre-dose | 231482.400 ng/mL | Standard Deviation 175589.7297 |