Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis (NCT NCT03312751)

Last Updated: 2024-03-12

Results Overview

The overall response rate (ORR) of patients achieving either Complete or Partial Response or HLH Improvement, at Week 8 or EOT (whichever occurs earlier).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

35 participants

Primary outcome timeframe

Up to Week 8

Results posted on

2024-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	16	19
Overall Study COMPLETED	9	9
Overall Study NOT COMPLETED	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Death	7	9
Overall Study Study discontinuation due to other reason	0	1

Baseline Characteristics

Study to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic Lymphohistiocytosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All-treated Analysis Set - Treatment naïve n=16 Participants 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.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.	Total n=35 Participants Total of all reporting groups
Age, Categorical <=18 years	16 Participants n=5 Participants	19 Participants n=7 Participants	35 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Body Weight (kg)	9.599 kg STANDARD_DEVIATION 10.5915 • n=5 Participants	13.946 kg STANDARD_DEVIATION 14.4351 • n=7 Participants	11.959 kg STANDARD_DEVIATION 12.8309 • n=5 Participants
Height/Length (cm)	67.02 cm STANDARD_DEVIATION 27.416 • n=5 Participants	83.41 cm STANDARD_DEVIATION 37.790 • n=7 Participants	75.96 cm STANDARD_DEVIATION 34.003 • n=5 Participants
Body Surface Area (m^2)	0.415 m^2 STANDARD_DEVIATION 0.3022 • n=5 Participants	0.564 m^2 STANDARD_DEVIATION 0.4141 • n=7 Participants	0.497 m^2 STANDARD_DEVIATION 0.3698 • n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Overall Response at Week 8 or End of Treatment (if Earlier)	62.9 Percentage of participants Interval 44.9 to 78.5	50.0 Percentage of participants Interval 24.7 to 75.3	73.7 Percentage of participants Interval 48.8 to 90.9

SECONDARY outcome

Timeframe: Up to 18 months

Population: 'All-treated analysis set - treatment experienced' includes a censored observation for 1 patient who discontinued the study early.

Number of patients surviving to the end of the study.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Overall Survival at End of Study Alive at end of study	19 Participants	9 Participants	10 Participants
Overall Survival at End of Study Early discontinuation	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Overall Survival to HSCT	25 Participants	12 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 1 year post HSCT

Population: All-treated analysis includes total number or patients who received HSCT.

Number of patients surviving post HSCT.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=23 Participants 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.	All-treated Analysis Set - Treatment naïve n=11 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=12 Participants 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.
Overall Survival for Patients Receiving HSCT	17 Participants	8 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 1 year post HSCT

Population: Analysis population based on the number of patients with 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.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=23 Participants 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.	All-treated Analysis Set - Treatment naïve n=11 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=12 Participants 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.
Event-free Survival	16 Participants	8 Participants	8 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Overall Response at Start of Conditioning Complete response	4 Participants	3 Participants	1 Participants
Overall Response at Start of Conditioning Partial response	11 Participants	5 Participants	6 Participants
Overall Response at Start of Conditioning HLH improvement	1 Participants	0 Participants	1 Participants
Overall Response at Start of Conditioning No response	19 Participants	8 Participants	11 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=28 Participants 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.	All-treated Analysis Set - Treatment naïve n=12 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=16 Participants 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.
Duration of Response	61 days Interval 29.0 to NA explanation: The upper CI could not be calculated as there were not enough subjects that had a response and subsequently lost that response in the observed time period	40 days Interval 19.0 to NA explanation: The upper CI could not be calculated as there were not enough subjects that had a response and subsequently lost that response in the observed time period	61 days Interval 21.0 to NA explanation. The upper CI could not be calculated as there were not enough subjects that had a response and subsequently lost that response in the observed time period

SECONDARY outcome

Timeframe: Up to 18 months

Population: Only patients with a response were included.

Time to first response at any time during the study.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=28 Participants 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.	All-treated Analysis Set - Treatment naïve n=12 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=16 Participants 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.
Time to Response	4 days Interval 4.0 to 13.0	5 days Interval 4.0 to 21.0	4 days Interval 4.0 to 30.0

SECONDARY outcome

Timeframe: Up to 6 months

Number of patients able to reduce glucocorticoids by 50% or more of the baseline dose during emapalumab treatment.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Number of Patients Reducing Glucocorticoids by 50% or More of the Baseline Dose During Emapalumab Treatment	15 Participants	8 Participants	7 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Number of patients able to proceed to HSCT when deemed indicated.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Number of Patients Proceeding to HSCT	23 Participants	11 Participants	12 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=20 Participants 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.	All-treated Analysis Set - Treatment naïve n=6 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=14 Participants 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.
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	-6.514 scale on a score Standard Deviation 14.8977	5.810 scale on a score Standard Deviation 19.8220
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	—	0.794 scale on a score Standard Deviation 4.8152
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	—	8.469 scale on a score Standard Deviation 9.6897
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	15.978 scale on a score	—
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 13.4760	—	-7.862 scale on a score Standard Deviation 13.4760

SECONDARY outcome

Timeframe: Up to 6 months

Population: Assessment completed at the end of treatment for those who proceeded/were planned to proceed to HSCT.

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)

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=15 Participants 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.	All-treated Analysis Set - Treatment naïve n=7 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=8 Participants 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.
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) Physical discomfort	10.0 scale on a score Standard Deviation 3.57	9.4 scale on a score Standard Deviation 2.99	10.5 scale on a score Standard Deviation 4.14
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) Cooperation/compliance	9.3 scale on a score Standard Deviation 3.02	9.6 scale on a score Standard Deviation 2.76	9.1 scale on a score Standard Deviation 3.4
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) Mood/behavior	20.4 scale on a score Standard Deviation 8.82	15.1 scale on a score Standard Deviation 8.88	25.0 scale on a score Standard Deviation 6.02
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	6.1 scale on a score Standard Deviation 2.48	5.5 scale on a score Standard Deviation 2.33
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) Activity	3.1 scale on a score Standard Deviation 1.22	2.7 scale on a score Standard Deviation 0.95	3.4 scale on a score Standard Deviation 1.41
Quality of Life Assessed Through Behavioral, Affective and Somatic Experiences Scales (BASES) Sleep	2.1 scale on a score Standard Deviation 1.04	1.8 scale on a score Standard Deviation 1.10	2.3 scale on a score Standard Deviation 1.03

SECONDARY outcome

Timeframe: Up to 18 months

Incidence of adverse events. SAE = serious adverse event; TEAE = treatment-emergent adverse event

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Serious TEAEs	32 Participants	16 Participants	16 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs with infusion-related reactions	7 Participants	3 Participants	4 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Non-TEAEs	15 Participants	5 Participants	10 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs	35 Participants	16 Participants	19 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs related to study drug	9 Participants	3 Participants	6 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Mild TEAEs	30 Participants	12 Participants	18 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Moderate TEAEs	27 Participants	12 Participants	15 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Severe TEAEs	31 Participants	15 Participants	16 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs leading to discontinuation of study drug	7 Participants	3 Participants	4 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs with an outcome of death	16 Participants	7 Participants	9 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Treatment-emergent SAEs related to study drug	4 Participants	2 Participants	2 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) TEAEs with infections	29 Participants	14 Participants	15 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Mild infections	21 Participants	10 Participants	11 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Moderate infections	15 Participants	8 Participants	7 Participants
Incidence, Severity, Causality and Outcomes of AEs (Serious and Non-serious) Severe infections	16 Participants	7 Participants	9 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Albumin: low to within	6 Participants	3 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Albumin: within to low	2 Participants	0 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Alkaline phosphatase: within to low	8 Participants	5 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Alkaline phosphatase: low to within	5 Participants	1 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Alanine aminotransferase: high to within	8 Participants	6 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Aspartate aminotransferase: within to high	3 Participants	0 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Aspartate aminotransferase: high to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Aspartate aminotransferase: high to within	8 Participants	5 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Bilirubin: within to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Bilirubin: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Bilirubin: high to within	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Creatinine: low to within	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Creatinine: within to low	5 Participants	1 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Creatinine: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Creatinine: high to within	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 C-reactive protein: within to high	6 Participants	2 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 C-reactive protein: high to within	4 Participants	1 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Ferritin: high to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Ferritin: high to within	5 Participants	3 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 γGT: within to high	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 γGT: high to within	4 Participants	3 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Glucose: within to high	2 Participants	2 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Glucose: high to within	8 Participants	4 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lactate dehydrogenase: low to within	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lactate dehydrogenase: within to high	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lactate dehydrogenase: high to within	8 Participants	5 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Triglycerides: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Triglycerides: high to within	5 Participants	3 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea: within to low	5 Participants	2 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea: within to high	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea: high to within	4 Participants	1 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea nitrogen: low to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea nitrogen: within to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Urea nitrogen: within to high	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Basophils: low to within	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Basophils: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Basophils: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Basophils/leukocytes: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Eosinophils: low to within	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Eosinophils: within to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Eosinophils/leukocytes: within to high	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Hematocrit: low to within	9 Participants	4 Participants	5 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Hematocrit: within to low	5 Participants	2 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Hemoglobin: low to within	9 Participants	5 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Hemoglobin: low to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Hemoglobin: within to low	5 Participants	1 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Large unstained cells: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes: low to within	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes: within to low	6 Participants	3 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes: within to high	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes/leukocytes: within to high	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes/leukocytes: within to low	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Lymphocytes/leukocytes: high to within	2 Participants	2 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes: low to within	6 Participants	2 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes: low to high	3 Participants	0 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes: within to low	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes: within to high	2 Participants	2 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes: high to within	2 Participants	0 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes/leukocytes: within to high	3 Participants	3 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Monocytes/leukocytes: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form: low to within	9 Participants	3 Participants	6 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form: within to low	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form: within to high	2 Participants	0 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form/leukocytes: low to within	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form/leukocytes: within to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Neutrophils band form/leukocytes: within to high	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Platelets: low to within	5 Participants	2 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Platelets: low to high	2 Participants	2 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Platelets: within to low	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Platelets: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Platelets: high to within	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Erythrocytes: low to within	8 Participants	4 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Erythrocytes: within to low	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Erythrocytes: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Leukocytes: low to within	9 Participants	2 Participants	7 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Leukocytes: low to high	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Leukocytes: within to low	4 Participants	3 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Leukocytes: high to within	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT: low to within	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT: within to low	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT: within to high	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT: high to within	4 Participants	3 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT ratio: low to within	2 Participants	0 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT ratio: within to low	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT ratio: within to high	2 Participants	0 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 aPTT ratio: high to within	2 Participants	2 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 D-dimer: within to high	4 Participants	0 Participants	4 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 D-dimer: high to within	6 Participants	4 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Fibrinogen: low to within	13 Participants	6 Participants	7 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Fibrinogen: low to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Fibrinogen: within to low	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Fibrinogen: within to high	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Fibrinogen: high to within	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Prothrombin time: within to high	3 Participants	1 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Prothrombin time: high to within	6 Participants	3 Participants	3 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Prothrombin INR: within to high	1 Participants	0 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Prothrombin INR: high to low	1 Participants	1 Participants	0 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Prothrombin INR: high to within	4 Participants	2 Participants	2 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Alkaline phosphatase: high to within	2 Participants	1 Participants	1 Participants
Evolution of Laboratory Parameters Change From Baseline to EOT/Week 8 Alanine aminotransferase: within to high	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 6 months

Number of patients who discontinued emapalumab treatment for safety reasons.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Number of Patients Who Discontinued Emapalumab Treatment	7 Participants	3 Participants	4 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

The serum concentration of emapalumab will be measured as a function of time to determine the emapalumab PK profile.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Serum Concentrations of Emapalumab Emapalumab serum concentration at Baseline pre-dose	14.311 ng/mL Standard Deviation 50.2717	12.899 ng/mL Standard Deviation 49.9589	15.425 ng/mL Standard Deviation 51.8562
Serum Concentrations of Emapalumab Emapalumab serum concentration at EOT/Week 8 pre-dose	258337.456 ng/mL Standard Deviation 231412.7632	295521.381 ng/mL Standard Deviation 296009.6195	231482.400 ng/mL Standard Deviation 175589.7297
Serum Concentrations of Emapalumab Emapalumab serum concentration at EOT/Week 8 post-dose	142338.620 ng/mL Standard Deviation 89464.1682	205599.340 ng/mL Standard Deviation NA Not calculable	79077.900 ng/mL Standard Deviation NA Not calculable

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Levels (in ng/L) of total IFNγ (interferon gamma), markers of its neutralization (CXCL9 and CXCL10), and sCD25.

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
Change in Pharmacodynamic Parameters Total IFNγ at baseline	1112.681 ng/L Standard Deviation 2393.9753	1356.191 ng/L Standard Deviation 2550.8868	920.436 ng/L Standard Deviation 2314.6502
Change in Pharmacodynamic Parameters Total IFNγ at EOT/Week 8	25708.836 ng/L Standard Deviation 41775.8890	39233.258 ng/L Standard Deviation 60957.7563	15941.198 ng/L Standard Deviation 14695.7764
Change in Pharmacodynamic Parameters CXCL10 at baseline	14195.394 ng/L Standard Deviation 37588.5073	28501.304 ng/L Standard Deviation 54928.0152	3654.197 ng/L Standard Deviation 7505.8959
Change in Pharmacodynamic Parameters CXCL10 at EOT/Week 8	3203.194 ng/L Standard Deviation 13239.6238	6355.428 ng/L Standard Deviation 20287.7247	926.580 ng/L Standard Deviation 2389.4231
Change in Pharmacodynamic Parameters CXCL9 at baseline	14113.999 ng/L Standard Deviation 34451.6041	26695.379 ng/L Standard Deviation 49400.5090	4181.331 ng/L Standard Deviation 6470.0963
Change in Pharmacodynamic Parameters CXCL9 at EOT/Week 8	2109.078 ng/L Standard Deviation 10100.8802	4749.055 ng/L Standard Deviation 15555.8338	202.428 ng/L Standard Deviation 240.9550
Change in Pharmacodynamic Parameters sCD25 at baseline	17026.171 ng/L Standard Deviation 13537.8951	23980.603 ng/L Standard Deviation 13267.5834	11535.830 ng/L Standard Deviation 11268.1072
Change in Pharmacodynamic Parameters sCD25 at EOT/Week 8	9882.585 ng/L Standard Deviation 8542.0418	11301.162 ng/L Standard Deviation 8847.8000	8858.058 ng/L Standard Deviation 8417.5485

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).

Outcome measures

Outcome measures
Measure	All-treated Analysis Set n=35 Participants 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.	All-treated Analysis Set - Treatment naïve n=16 Participants Patients in the All-treated analysis set who were naïve to HLH treatment.	All-treated Analysis Set - Treatment Experienced n=19 Participants 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.
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	2 Participants	0 Participants
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	0 Participants	1 Participants

Adverse Events

All-treated Analysis Set - Treatment naïve

Serious events: 16 serious events

Other events: 14 other events

Deaths: 7 deaths

All-treated Analysis Set - Treatment Experienced

Serious events: 16 serious events

Other events: 19 other events

Deaths: 9 deaths

All-treated Analysis Set

Serious events: 32 serious events

Other events: 35 other events

Deaths: 16 deaths

Serious adverse events

Other adverse events

Additional Information

Radmila Kanceva, MD, Medicine Development Lead

Swedish Orphan Biovitrum AG

Phone: +41 793048899

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place