Trial Outcomes & Findings for A Study for Long-term Follow-up of Hemophagocytic Lymphohistiocytosis (HLH) Participants Who Received Treatment With Emapalumab (NI-0501), an Anti-interferon Gamma Monoclonal Antibody (NCT NCT02069899)

NCT ID: NCT02069899

Last Updated: 2022-06-28

Results Overview

Adverse events were defined as any undesirable experience occurring in a participant during the study, whether or not considered related to emapalumab.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

58 participants

Primary outcome timeframe

From the date of enrollment in this study up to 1 year either after HSCT or after the last administration of emapalumab (maximum duration: 639 days)

Results posted on

2022-06-28

Participant Flow

Participants with hemophagocytic lymphohistiocytosis (HLH) who had received at least 1 dose of emapalumab in the context of a previous emapalumab clinical study (Study NI-0501-04 \[NCT01818492\] or Study NI-0501-06 \[NCT03311854\]) in which no long-term follow-up was planned, and participants who received emapalumab through a compassionate use (CU) were enrolled in the current study (NI-0501-05, NCT02069899).

Participant milestones

Participant milestones
Measure	Enrolled-04 Cohort Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after haematopoietic stem cell transplantation (HSCT) or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Overall Study STARTED	37	14	7
Overall Study Treated in Current Study	22	0	5
Overall Study COMPLETED	24	13	4
Overall Study NOT COMPLETED	13	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Enrolled-04 Cohort Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after haematopoietic stem cell transplantation (HSCT) or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Overall Study Adverse Event	6	0	1
Overall Study Withdrawal by Participant	2	0	0
Overall Study Lost to Follow-up	1	0	1
Overall Study Other	4	0	0
Overall Study Participant could not travel to the study site due to Covid restrictions	0	1	0
Overall Study Participant was withdrawn to receive emapalumab again in CU and then subsequently died	0	0	1

Baseline Characteristics

Ethnicity not collected

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Enrolled-04 Cohort n=37 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort n=14 Participants All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort n=7 Participants In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.	Total n=58 Participants Total of all reporting groups
Age, Categorical <=18 years	37 Participants n=37 Participants	13 Participants n=14 Participants	7 Participants n=7 Participants	57 Participants n=58 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=37 Participants	1 Participants n=14 Participants	0 Participants n=7 Participants	1 Participants n=58 Participants
Age, Categorical >=65 years	0 Participants n=37 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	0 Participants n=58 Participants
Sex: Female, Male Female	19 Participants n=37 Participants	10 Participants n=14 Participants	4 Participants n=7 Participants	33 Participants n=58 Participants
Sex: Female, Male Male	18 Participants n=37 Participants	4 Participants n=14 Participants	3 Participants n=7 Participants	25 Participants n=58 Participants
Race/Ethnicity, Customized Race · White/Caucasian	27 Participants n=37 Participants	11 Participants n=14 Participants	5 Participants n=7 Participants	43 Participants n=58 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=37 Participants	0 Participants n=14 Participants	1 Participants n=7 Participants	5 Participants n=58 Participants
Race/Ethnicity, Customized Race · Black/African descent	3 Participants n=37 Participants	2 Participants n=14 Participants	1 Participants n=7 Participants	6 Participants n=58 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=37 Participants	0 Participants n=14 Participants	0 Participants n=7 Participants	3 Participants n=58 Participants
Race/Ethnicity, Customized Race · Not collected/Missing	0 Participants n=37 Participants	1 Participants n=14 Participants	0 Participants n=7 Participants	1 Participants n=58 Participants
Ethnicity	—	—	—	0 Participants Ethnicity not collected

PRIMARY outcome

Timeframe: From the date of enrollment in this study up to 1 year either after HSCT or after the last administration of emapalumab (maximum duration: 639 days)

Population: Participants who previously received treatment in a parent study (NI-0501-04 or NI-0501-06) or under compassionate use and who provided informed consent for participation in Study NI-0501-05.

Adverse events were defined as any undesirable experience occurring in a participant during the study, whether or not considered related to emapalumab.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=37 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort n=14 Participants All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort n=7 Participants In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Number of Participants With Adverse Event (AE)	37 Participants	12 Participants	7 Participants

SECONDARY outcome

Timeframe: From 1st achievement of overall response until HSCT or last treatment date if participant did not undergo HSCT (maximum 250 days)

Cumulative duration of response: total number of days in response from 1st achievement of overall response until HSCT or last treatment date if the participant did not undergo HSCT. Overall response: achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI). CR: no fever, normal spleen size, no cytopenia (absolute neutrophil count \[ANC\] ≥1.0 x 10\^9/L and platelet count ≥ 100 x 10\^9/L), no hyperferritinemia (serum ferritin \<2000 μg/L), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and cerebrospinal fluid \[CSF\] abnormalities attributed to HLH, no sustained worsening of soluble cluster of differentiation (CD) 25. PR: at least 3 HLH clinical and laboratory criteria (including central nervous system \[CNS\] abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory abnormalities (including CNS involvement).

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=36 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Cumulative Duration of Response (Enrolled-04 Cohort)	70.7 days Standard Deviation 56.35	—	—

SECONDARY outcome

Timeframe: From first date of response and first date of loss of response or death (maximum 416 days)

Duration of first response was defined as the number of days between first date of response and first date of loss of response or death. Response was defined as macrophage activation syndrome (MAS) remission, which was resolution of clinical signs and symptoms according to the Investigator (MAS clinical signs and symptoms score ≤ 1) and normalization of laboratory parameters relevant to MAS as follows: white blood cells (WBC) and platelet count above the upper limit of normal (LLN), Lactate dehydrogenase \< 1.5 × lower limit of normal (ULN), aspartate aminotransferase/alanine aminotransferase \<1.5 × ULN, fibrinogen \> 100 mg/dL, ferritin level decreased by at least 80% from values at screening or baseline (whichever was higher) or \< 2000 ng/mL, whichever was lower.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=13 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Duration of First Response (Enrolled-06 Cohort)	61.0 days Interval 9.0 to 358.0	—	—

SECONDARY outcome

Timeframe: From the date of last of emapalumab dose to the date of death or last contact or 12 months after last dose, whichever came first (maximum 366 days)

Overall survival was defined as time from the date of the last emapalumab dose to the date of death. Participants without an event were censored at the time of last contact or 12 months after last dose (whichever came first). As some participants had their last emapalumab dose in the parent study (NI-0501-04), data from both NI-0501-05 and NI-0501-04 studies were considered for the assessment of overall survival. Kaplan-Meier methodology was used for estimation.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=37 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Overall Survival (Enrolled-04 Cohort)	NA days Median and Inter-Quartile Range was not reached due to low number of events.	—	—

SECONDARY outcome

Timeframe: From the date of last of emapalumab dose to the date of death or last contact or 12 months after last dose, whichever came first (maximum 366 days)

Overall survival was defined as time from the date of last emapalumab dose to the date of death. Participants without an event were censored at the time of last contact or 12 months after last dose (whichever came first). As participants in the Enrolled-06 Cohort did not receive emapalumab in the current study, data from both NI-0501-05 and NI-0501-06 studies were considered for the assessment of overall survival. Kaplan-Meier methodology was used for estimation.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=14 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Overall Survival (Enrolled-06 Cohort)	NA days Median and Inter-Quartile Range was not reached due to no event.	—	—

SECONDARY outcome

Timeframe: From HSCT up to 12 months

For participants who underwent HSCT either in parent study (NI-0501-04) or current study (NI-0501-05), engraftment rate was based on the number of participants experiencing primary or secondary graft failure (blood stem cell transplant failure, engraft failure, or transplant dysfunction), as reported as an adverse event.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=29 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Percentage of Participants Who Achieved Engraftment (Enrolled-04 Cohort)	20.7 percentage of participants Interval 9.8 to 38.4	—	—

SECONDARY outcome

Timeframe: From HSCT to 12 months

For participants who underwent HSCT, achievement of donor chimerism was considered based on donor chimerism in peripheral blood completed, that is, donor cells \>95%.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=29 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Percentage of Participants Who Achieved Donor Chimerism (Enrolled-04 Cohort)	72.4 percentage of participants Interval 54.3 to 85.3	—	—

SECONDARY outcome

Timeframe: From HSCT to 12 months

Occurrence of graft-versus-host-disease, reported in Study NI-0501-05 as an AE.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=29 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Percentage of Participants With Graft-versus-host-disease (Enrolled-04 Cohort)	24.1 percentage of participants Interval 12.2 to 42.1	—	—

SECONDARY outcome

Timeframe: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study

MAS activity was monitored using a visual analogue scale ranging from 0 to 10 with a higher score indicted higher disease activity.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=13 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort) Baseline	0.0 score on a scale Standard Deviation 0.0	—	—
MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort) Day 100	0.0 score on a scale Standard Deviation 0.0	—	—
MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort) Month 12/End of Study	0.2 score on a scale Standard Deviation 0.48	—	—

SECONDARY outcome

Timeframe: First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, last infusion day (infusion Day 188), 12 months post-transplant

Population: Enrolled-04 population included participants previously enrolled and treated in Study NI-0501-04 (participants with primary HLH) who provided informed consent for participation in Study NI-0501-05 and who had data available for specified timepoints. Circulating emapalumab level post-transplant included participants who had HSCT and data available at 12 months post-HSCT (Samples were not to be taken once it had been determined that emapalumab was below measurable level of 62.5 µg/L).

Circulating Emapalumab level in Enrolled-04 Cohort who continued to receive treatment with emapalumab in the current study (NI-0501-05).

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=22 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Circulating Emapalumab Level (Enrolled-04 Cohort) Infusion Day 1	165148.4 µg/L Standard Deviation 175057.98	—	—
Circulating Emapalumab Level (Enrolled-04 Cohort) Infusion Day 188	157849.0 µg/L Standard Deviation 66180.28	—	—
Circulating Emapalumab Level (Enrolled-04 Cohort) 12 months post-transplant	80.5 µg/L Standard Deviation 43.52	—	—

SECONDARY outcome

Timeframe: Baseline (first NI-0501-05 visit), Day 100, Month 6

Population: Enrolled-06 population included participants previously enrolled and treated in Study NI-0501-06 (participants with MAS in Still's disease) who provided informed consent for participation in Study NI-0501-05 and had available data at specified timepoints (Samples were not to be taken once it had been determined that emapalumab was below measurable level of 62.5 µg/L).

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=12 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Circulating Emapalumab Level (Enrolled-06 Cohort) Baseline	20968.0 µg/L Standard Deviation 18226.14	—	—
Circulating Emapalumab Level (Enrolled-06 Cohort) Day 100	8515.3 µg/L Standard Deviation 6814.50	—	—
Circulating Emapalumab Level (Enrolled-06 Cohort) Month 6	1628.5 µg/L Standard Deviation 1427.46	—	—

SECONDARY outcome

Timeframe: First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, Day 100 post-transplant, 12 months post-transplant

Population: Enrolled-04 population included participants previously enrolled and treated in Study NI-0501-04 (participants with primary HLH) who provided informed consent for participation in Study NI-0501-05 and who had data available for specified timepoints. Total human interferon gamma levels post-transplant included participants who underwent HSCT and data available at Day 100 and 12 months post-HSCT.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=24 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Total Human Interferon Gamma Levels (Enrolled-04 Cohort) Infusion Day 1	5290.4 ng/L Standard Deviation 4992.27	—	—
Total Human Interferon Gamma Levels (Enrolled-04 Cohort) Day 100 post-transplant	3613.6 ng/L Standard Deviation 6052.31	—	—
Total Human Interferon Gamma Levels (Enrolled-04 Cohort) 12 months post-transplant	447.4 ng/L Standard Deviation 1096.99	—	—

SECONDARY outcome

Timeframe: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=13 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Total Human Interferon Gamma Levels (Enrolled-06 Cohort) Baseline	5544.3 ng/L Standard Deviation 8285.12	—	—
Total Human Interferon Gamma Levels (Enrolled-06 Cohort) Day 100	2958.7 ng/L Standard Deviation 6762.62	—	—
Total Human Interferon Gamma Levels (Enrolled-06 Cohort) Month 12/End of Study	1111.0 ng/L Standard Deviation 1311.04	—	—

SECONDARY outcome

Timeframe: From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days)

Population: Participants who previously received treatment in a parent study (NI-0501-04 or NI-0501-06) or under CU and who provided informed consent for participation in Study NI-0501-05. Number of participants analysed included participants who had available data for anti-drug antibody.

Outcome measures

Outcome measures
Measure	Enrolled-04 Cohort n=32 Participants Participants enrolled in Study NI-0501-04 were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. For participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT was delayed for reasons unrelated to the administration of emapalumab, they could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05) at the request of the investigator, providing a favorable benefit/risk assessment of treatment was established. Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of this study (NI-0501-05), the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose was administered, if necessary.	Enrolled-06 Cohort n=14 Participants All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 were invited to participate for long-term follow-up for 1 year after the last administration of emapalumab. Participants did not receive emapalumab in the current study (NI-0501-05).	Enrolled-CU Cohort n=7 Participants In exceptional cases, at the spontaneous request of a treating physician, CU treatment was granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who received at least 1 dose of emapalumab were invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants could have continued treatment in the context of the current Study (NI-0501-05) while stem cell donor search was ongoing, or if the investigator assessed that continuation of treatment was beneficial.
Number of Participants With Anti-drug Antibody	1 Participants	3 Participants	0 Participants

Adverse Events

Enrolled-04 Cohort

Serious events: 28 serious events

Other events: 37 other events

Deaths: 9 deaths

Enrolled-06 Cohort

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Enrolled-CU Cohort

Serious events: 6 serious events

Other events: 7 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Radmila Kanceva/Senior Medical Director Immunology

Sobi AG

Phone: + 41 22 551 91 63

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review results communication prior to public release. The PI shall consider the comments received from the sponsor and shall delete any confidential information. The sponsor may require the delay of publication submission if it contains any patentable subject matter which requires protection.
Publication restrictions are in place

Restriction type: OTHER