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Clinical Trial Results:
A multicentre study for the long-term follow-up of HLH patients who received treatment with NI-0501, an anti-interferon gamma monoclonal antibody

Summary
EudraCT number	2012-005753-23
Trial protocol	IT CZ DE ES AT SE GB FR NL
Global end of trial date	18 May 2021

Results information
Results version number	v1(current)
This version publication date	21 Jul 2022
First version publication date	21 Jul 2022
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

NI-0501-05

ISRCTN number

US NCT number

NCT02069899

WHO universal trial number (UTN)

Other trial identifiers

US IND: 111015

Sponsor organisation name

Swedish Orphan Biovitrum

Sponsor organisation address

12 Chemin des Aulx, Plan les Ouates, Switzerland, 1228

Public contact

Radmila Kanceva/Senior Medical Director Immunology, Sobi AG , +46 8697 2000, Radmila.Kanceva@sobi.com

Scientific contact

Radmila Kanceva/Medical Development Lead Immunology, Sobi AG , +46 8697 2000, Radmila.Kanceva@sobi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

09 Jul 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

18 May 2021

Global end of trial reached?

Yes

Global end of trial date

18 May 2021

Was the trial ended prematurely?

Main objective of the trial

• To monitor the long-term safety profile of NI-0501, hereafter referred to as emapalumab • To assess hemophagocytic lymphohistiocytosis (HLH) participants’ survival after emapalumab treatment • To assess duration of response to emapalumab treatment (i.e., maintenance of HLH control) • To assess post-hematopoietic stem cell transplantation (HSCT) outcome measures, if applicable • To assess background disease activity in participants with secondary forms of HLH • To study the elimination profile of emapalumab • To evaluate the pharmacodynamic effects (levels of circulating total interferon gamma [IFNγ]) • To assess the immunogenicity of emapalumab

Protection of trial subjects

The informed consent form had to be signed by the participant (as required by local law) or by the participant's parents or legally authorized representative prior to any study-related procedures, with the assent of participants who were deemed suitable to provide it, as applicable. Written informed consent/assent was obtained from all participants or their parents/legally authorized representative prior to enrolment into the study, as dictated by the Declaration of Helsinki. The method of obtaining and documenting informed consent and the contents of the consent complied with International Conference on Harmonisation-Good Clinical Practice and all applicable regulatory requirement(s).

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Aug 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Italy: 26

Country: Number of subjects enrolled

United States: 24

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The Enrolled-04 cohort comprised 37 patients treated in Study NI-0501-04, and the Enrolled-06 cohort comprised 14 patients treated in Study NI-0501-06. The Enrolled-CU cohort comprised 7 patients who had previously been treated through a compassionate use (CU) request and were not treated in either Study NI-0501-04 or NI-0501-06.

Screening details

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

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Enrolled-04 Cohort

Arm description

Participants enrolled in Study NI-0501-04 were invited to participate in long-term follow-up for 1 year after either HSCT or 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. Participants for whom an appropriate donor was not identified by Week 8, or in cases where HSCT was delayed for reasons unrelated to the administration of emapalumab, could continue receiving treatment with emapalumab beyond the foreseen 8 weeks in 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 Study NI-0501-05, the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study, or an adjusted dose was administered.

Arm type

Interventional for selected participants

Investigational medicinal product name

Emapalumab

Investigational medicinal product code

Other name

NI-0501

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Treatment with emapalumab was not planned for all enrolled participants. For participants who continued receiving emapalumab in the context of 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

Arm description

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).

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Enrolled-CU Cohort

Arm description

In exceptional cases, at the spontaneous request of a treating physician, compassionate use (CU) treatment with emapalumab was granted to 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 under these circumstances were invited to participate for long-term follow-up for 1 year after either HSCT or the last administration of emapalumab. Participants could have continued treatment with emapalumab 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.

Arm type

Interventional for selected participants

Investigational medicinal product name

Emapalumab

Investigational medicinal product code

Other name

NI-0501

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Number of subjects in period 1	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Started	37	14	7
Treated with emapalumab in current study	22 ^[1]	0 ^[2]	5
Completed	24	13	4
Not completed	13	1	3
Consent withdrawn by subject	2	-	-
Adverse event, non-fatal	6	-	1
Serious adverse event, fatal	1	-	-
No matching reasons found	-	1	-
Withdrew to receive emapalumab in Study NI-0501-CU	-	-	1
Lost to follow-up	1	-	1
Patient transferred to receive transplant	1	-	-
Early termination	1	-	-
Patient death	1	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 22 participants in the Enrolled-04 Cohort were treated with emapalumab in the current study; being treated with emapalumab was not a criterion for study completion.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: No participants in the Enrolled-06 Cohort were treated with emapalumab in the current study; being treated with emapalumab was not a criterion for study completion.

Baseline characteristics

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Reporting group title

Enrolled-04 Cohort

Reporting group description

Reporting group title

Enrolled-06 Cohort

Reporting group description

Reporting group title

Enrolled-CU Cohort

Reporting group description

Reporting group values	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort	Total
Number of subjects	37	14	7	58
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	24	0	4	28
Children (2-11 years)	13	8	3	24
Adolescents (12-17 years)	0	5	0	5
Adults (18-64 years)	0	1	0	1
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age continuous
Units: years
median (full range (min-max))	1 (0.2 to 10.2)	12 (2.2 to 25.5)	1.7 (0.6 to 10.6)	-
Gender categorical
Units: Subjects
Female	19	10	4	33
Male	18	4	3	25
Race
Units: Subjects
White/Caucasian	27	11	5	43
Asian	4	0	1	5
Black/African descent	3	2	1	6
Other	3	0	0	3
Not collected/missing	0	1	0	1

End points

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Reporting group title

Enrolled-04 Cohort

Reporting group description

Reporting group title

Enrolled-06 Cohort

Reporting group description

Reporting group title

Enrolled-CU Cohort

Reporting group description

Primary: Number of Participants With Adverse Events

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End point title

Number of Participants With Adverse Events ^[1]

End point description

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

End point type

Primary

End point timeframe

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

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was carried out; this end point was the number of participants with an adverse event during the study.

End point values	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Number of subjects analysed	37	14	7
Units: Participants	37	12	7

No statistical analyses for this end point

Secondary: Cumulative Duration of Response

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End point title

Cumulative Duration of Response ^[2]

End point description

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).

End point type

Secondary

End point timeframe

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

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Data were available only for participants in the Enrolled-04 Cohort.

End point values	Enrolled-04 Cohort
Number of subjects analysed	37
Units: day
arithmetic mean (standard deviation)	70.7 ± 56.35

No statistical analyses for this end point

Secondary: Duration of First Response

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End point title

Duration of First Response ^[3]

End point description

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 lower limit of normal (LLN), lactate dehydrogenase <1.5 × upper 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.

End point type

Secondary

End point timeframe

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

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only data from Enrolled-06 Cohort were available.

End point values	Enrolled-06 Cohort
Number of subjects analysed	14
Units: day
median (inter-quartile range (Q1-Q3))	61 (9.00 to 358.00)

No statistical analyses for this end point

Secondary: Overall Survival: Number of Participants Alive

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End point title

Overall Survival: Number of Participants Alive

End point description

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 some participants had their last emapalumab dose in the parent study, data from NI-0501-04, NI-0501-05 and NI-0501-06 studies were considered for the assessment of overall survival. Kaplan-Meier methodology was used for estimation. Median overall survival was not reached in any of the groups as 28 of the 37 participants (75.7%) in the Enrolled-04 Cohort, all 14 participants (100.0%) in the Enrolled-06 Cohort, and 5 participants (71.4%) were alive at last observation or 12 months post last dose, whichever came first.

End point type

Secondary

End point 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)

End point values	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Number of subjects analysed	37	14	7
Units: Participants	28	14	2

No statistical analyses for this end point

Secondary: Post-HSCT outcome indices

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End point title

Post-HSCT outcome indices ^[4]

End point description

Engraftment failure 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. Achievement of donor chimerism was considered based on donor chimerism in peripheral blood completed, that is, donor cells >95%. The number of participants who reported graft-versus-host-disease as an AE in Study NI-0501-05 provided the occurrence of graft-versus-host-disease.

End point type

Secondary

End point timeframe

From HSCT to 12 months post-HSCT

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only participants in the Enrolled-04 and Enrolled-CU cohorts underwent HSCT.

End point values	Enrolled-04 Cohort	Enrolled-CU Cohort
Number of subjects analysed	29 ^[5]	2 ^[6]
Units: Participants
number (not applicable)
Engraftment failure rate	6	1
Achievement of donor chimerism	22	0
Occurrence of graft-versus-host-disease	7	2

Notes
[5] - Of the 37 participants, 29 (78.4%) underwent HSCT
[6] - Of the 7 participants, 2 (28.6%) underwent HSCT

No statistical analyses for this end point

Secondary: Background Disease Activity: Macrophage Activation Syndrome in sHLH participants

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End point title

Background Disease Activity: Macrophage Activation Syndrome in sHLH participants ^[7]

End point description

MAS activity was monitored using a visual analog scale (VAS) ranging from 0 to 10 with a higher score indicating higher disease activity.

End point type

Secondary

End point timeframe

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

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is relevant only to participants in the Enrolled-06 Cohort.

End point values	Enrolled-06 Cohort
Number of subjects analysed	14 ^[8]
Units: Score on a scale
arithmetic mean (standard deviation)
Baseline	0 ± 0
Day 100	0 ± 0
Month 12/End of Study	0.2 ± 0.48

Notes
[8] - Baseline: 13 participants Day 100: 12 participants Month 12/End of Study: 13 participants

No statistical analyses for this end point

Secondary: Circulating Emapalumab Levels: Enrolled-04 Cohort

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End point title

Circulating Emapalumab Levels: Enrolled-04 Cohort ^[9]

End point description

Circulating emapalumab levels in participants who continued to receive treatment with emapalumab in the current study (NI-0501-05). Samples were not taken once it had been determined that emapalumab was below the measurable level of of 62.5 µg/L.

End point type

Secondary

End point timeframe

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

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is relevant only to participants in the Enrolled-04 Cohort.

End point values	Enrolled-04 Cohort
Number of subjects analysed	37 ^[10]
Units: µg/L
arithmetic mean (standard deviation)
First infusion day (Infusion Day 1)	165148.4 ± 175057.98
Last infusion day (Infusion Day 188)	157849.0 ± 66180.28
12 months post-transplant	80.5 ± 43.52

Notes
[10] - Day 1: 22 participants Day 188: 2 participants 12 months post-transplant: 12 participants

No statistical analyses for this end point

Secondary: Circulating Emapalumab Levels: Enrolled-06 Cohort

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End point title

Circulating Emapalumab Levels: Enrolled-06 Cohort ^[11]

End point description

Circulating emapalumab levels in the Enrolled-06 Cohort who did not continue to receive treatment with emapalumab in the current study (NI-0501-05). Samples were not taken once it had been determined that emapalumab was below the measurable level of 62.5 µg/L.

End point type

Secondary

End point timeframe

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

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is relevant only to participants in the Enrolled-06 Cohort.

End point values	Enrolled-06 Cohort
Number of subjects analysed	14 ^[12]
Units: μg/L
arithmetic mean (standard deviation)
Baseline (first NI-0501-05 visit)	20968.0 ± 18226.14
Day 100	8515.3 ± 6814.50
Month 6	1628.5 ± 1427.46

Notes
[12] - Baseline: 12 participants Day 100: 10 participants Month 6: 8 participants

No statistical analyses for this end point

Secondary: Total Human Interferon Gamma Levels: Enrolled-04 Cohort

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End point title

Total Human Interferon Gamma Levels: Enrolled-04 Cohort ^[13]

End point description

Concentrations of human interferon gamma (IFNγ) levels for participants in the Enrolled-04 Cohort. IFNγ concentrations post-dose are the sum of free and bound IFNγ. It should be noted that participants had already been treated with emapalumab at the time of enrollment into Study NI-0501-05. In addition, the number of observations and median values fluctuated, as the duration and the timing of the PD samples varied between participants.

End point type

Secondary

End point timeframe

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

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is relevant only to participants in the Enrolled-04 Cohort.

End point values	Enrolled-04 Cohort
Number of subjects analysed	37 ^[14]
Units: ng/L
arithmetic mean (standard deviation)
First infusion day (Infusion Day 1)	5290.4 ± 4992.27
Day 100 post-transplant	3613.6 ± 6052.31
12 months post-transplant	447.4 ± 1096.99

Notes
[14] - Infusion Day 1: 11 participants Day 100 post-transplant: 23 participants 12 months:24 participants

No statistical analyses for this end point

Secondary: Total Human Interferon Gamma Levels: Enrolled-06 Cohort

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End point title

Total Human Interferon Gamma Levels: Enrolled-06 Cohort ^[15]

End point description

Concentrations of IFNγ levels for participants in the Enrolled-06 Cohort. IFNγ concentrations post-dose are the sum of free and bound IFNγ. It should be noted that participants had already been treated with emapalumab at the time of enrollment into Study NI-0501-05.

End point type

Secondary

End point timeframe

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

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is relevant only to participants in the Enrolled-06 Cohort.

End point values	Enrolled-06 Cohort
Number of subjects analysed	13 ^[16]
Units: ng/L
arithmetic mean (standard deviation)
Baseline	5544.3 ± 8285.12
Day 100	2958.7 ± 6762.6
Month 12/End of Study	1111.0 ± 1311.04

Notes
[16] - Baseline: 13 participants Day 100: 12 participants Month 12/End of Study: 9 participants

No statistical analyses for this end point

Secondary: Number of Participants with Antidrug Antibodies

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End point title

Number of Participants with Antidrug Antibodies

End point description

The number of participants in which antidrug antibodies (ADA)-confirmed positive samples were noted.

End point type

Secondary

End point timeframe

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

End point values	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Number of subjects analysed	32	14	7
Units: Participants	1	3	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

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

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Enrolled-04 Cohort

Reporting group description

Participants enrolled in Study NI-0501-04 were invited to participate in long-term follow-up for 1 year either after HSCT or 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 cases 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 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 Study NI-0501-05, the dose and timing was either carried forward from the last administered emapalumab dose as part of the parent study, or an adjusted dose was administered.

Reporting group title

Enrolled-06 Cohort

Reporting group description

Reporting group title

Enrolled-CU Cohort

Reporting group description

In exceptional cases, at the spontaneous request of a treating physician, compassionate use (CU) treatment with emapalumab 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 under these circumstances 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 with emapalumab 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.

Serious adverse events	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Total subjects affected by serious adverse events
subjects affected / exposed	28 / 37 (75.68%)	3 / 14 (21.43%)	6 / 7 (85.71%)
number of deaths (all causes)	9	0	2
number of deaths resulting from adverse events	9	0	2
Vascular disorders
Circulatory collapse
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Hypertension
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shock
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Condition aggravated
subjects affected / exposed	5 / 37 (13.51%)	1 / 14 (7.14%)	2 / 7 (28.57%)
occurrences causally related to treatment / all	0 / 6	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	6 / 37 (16.22%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 8	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Acute graft versus host disease in intestine
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaphylactic reaction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Engraftment syndrome
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pulmonary alveolar haemorrhage
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1
Pulmonary oedema
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
Device breakage
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Blood stem cell transplant failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Engraft failure
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Right ventricular dysfunction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Neurological decompensation
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Subdural hygroma
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Coombs positive haemolytic anaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombotic microangiopathy
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Eye movement disorder
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumatosis intestinalis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Autoimmune hepatitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myositis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Still's disease
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ear infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enterococcal infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epstein-Barr virus infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gianotti-Crosti syndrome
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Klebsiella sepsis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia cytomegaloviral
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudomonal sepsis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	2 / 7 (28.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Staphylococcal sepsis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Enrolled-04 Cohort	Enrolled-06 Cohort	Enrolled-CU Cohort
Total subjects affected by non serious adverse events
subjects affected / exposed	37 / 37 (100.00%)	12 / 14 (85.71%)	7 / 7 (100.00%)
Vascular disorders
Flushing
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Hyperaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Hypertension
subjects affected / exposed	9 / 37 (24.32%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	9	0	1
Hypotension
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	5	0	1
General disorders and administration site conditions
Catheter site pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Complication associated with device
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Complication of device insertion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Condition aggravated
subjects affected / exposed	5 / 37 (13.51%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	6	0	2
Face oedema
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Fatigue
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Fibrosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gait disturbance
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Influenza like illness
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Localised oedema
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Mucosal inflammation
subjects affected / exposed	7 / 37 (18.92%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	7	0	0
Oedema
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	0	0
Pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pyrexia
subjects affected / exposed	17 / 37 (45.95%)	1 / 14 (7.14%)	1 / 7 (14.29%)
occurrences all number	26	1	2
Swelling face
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Visceral pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Xerosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Immune system disorders
Acute graft versus host disease in skin
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Allergy to immunoglobulin therapy
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Bacille Calmette-Guerin scar reactivation
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Engraftment syndrome
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Food allergy
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Graft versus host disease
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Graft versus host disease in gastrointestinal tract
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Graft versus host disease in liver
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Graft versus host disease in skin
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	4	0	1
Reproductive system and breast disorders
Scrotal swelling
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	1
Cough
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	0	0
Dysphonia
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Dyspnoea
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Epistaxis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Haemothorax
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Lung infiltration
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Nasal congestion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Nasal flaring
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 37 (2.70%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	1	1	0
Pleural effusion
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Pneumothorax
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pulmonary haemorrhage
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Pulmonary hypertension
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pulmonary mass
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Respiratory distress
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	1
Respiratory failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Sinus congestion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Sleep apnoea syndrome
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Sneezing
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Tachypnoea
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Irritability
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	7	0	0
Major depression
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Restlessness
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Separation anxiety disorder
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Investigations
Acinetobacter test positive
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Adenovirus test positive
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Alanine aminotransferase increased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Atypical mycobacterium test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
BK polyomavirus test positive
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Blood albumin decreased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Blood creatinine increased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Blood electrolytes abnormal
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Blood immunoglobulin G decreased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	0	0
Campylobacter test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Candida test positive
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Clostridium test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Cytomegalovirus test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Herpes simplex test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Human rhinovirus test positive
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Klebsiella test positive
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Mycobacterium test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Neutrophil count decreased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	8	0	0
Norovirus test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Oxygen saturation decreased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pseudomonas test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Respirovirus test positive
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Roseolovirus test positive
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Transaminases increased
subjects affected / exposed	4 / 37 (10.81%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	0	0
Ubiquinone decreased
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Urine output increased
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Injury, poisoning and procedural complications
Adverse event following immunisation
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Allergic transfusion reaction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Arthropod bite
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Blood stem cell transplant failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Burns first degree
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Contusion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Engraft failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Femoral neck fracture
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Foot fracture
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Infusion related reaction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin abrasion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin laceration
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Subdural haematoma
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Torus fracture
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Transfusion reaction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Transplant dysfunction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Unintentional medical device removal
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Vascular access complication
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Congenital, familial and genetic disorders
Sickle cell trait
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Cardiac disorders
Bradycardia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Cyanosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Left ventricular hypertrophy
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pericardial effusion
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Right ventricular dysfunction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Tachycardia
subjects affected / exposed	6 / 37 (16.22%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	9	0	0
Nervous system disorders
Epilepsy
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Headache
subjects affected / exposed	2 / 37 (5.41%)	2 / 14 (14.29%)	0 / 7 (0.00%)
occurrences all number	2	2	0
Hydrocephalus
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hypotonia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Neuralgia
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Nystagmus
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Opisthotonus
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Paraesthesia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pleocytosis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Seizure
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Somnolence
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Subdural effusion
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Haemolytic anaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Increased tendency to bruise
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Iron deficiency anaemia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Lymphocytosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Lymphopenia
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Macrocytosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Neutropenia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Thrombotic microangiopathy
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Eye disorders
Dry eye
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Eye movement disorder
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Maculopathy
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Ocular hyperaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Periorbital oedema
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Retinal disorder
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Retinal ischaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Vision blurred
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Abdominal pain
subjects affected / exposed	8 / 37 (21.62%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	9	0	0
Ascites
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Constipation
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Dental caries
subjects affected / exposed	0 / 37 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)
occurrences all number	0	2	0
Diarrhoea
subjects affected / exposed	11 / 37 (29.73%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	17	0	0
Diverticulum
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Duodenal ulcer
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Enterocolitis haemorrhagic
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Gastric mucosa erythema
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastritis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Haematochezia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Lip ulceration
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Nausea
subjects affected / exposed	3 / 37 (8.11%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	4	1	0
Oral mucosal discolouration
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Oral pain
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Pancreatitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	1
Rectal prolapse
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	2	0
Stomatitis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Tongue ulceration
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Umbilical hernia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Vomiting
subjects affected / exposed	9 / 37 (24.32%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	17	0	0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 37 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)
occurrences all number	0	2	0
Drug-induced liver injury
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hepatic steatosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hyperbilirubinaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hyperplastic cholecystopathy
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	2
Dermatitis allergic
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Dermatitis contact
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Drug eruption
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Drug reaction with eosinophilia and systemic symptoms
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Dry skin
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Erythema
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Hyperhidrosis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Ingrowing nail
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Panniculitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Papule
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Petechiae
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	0	0
Pruritus
subjects affected / exposed	5 / 37 (13.51%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	5	0	0
Rash
subjects affected / exposed	7 / 37 (18.92%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	11	0	1
Rash erythematous
subjects affected / exposed	5 / 37 (13.51%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	6	1	0
Rash macular
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Rash maculo-papular
subjects affected / exposed	5 / 37 (13.51%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	9	0	0
Rash papular
subjects affected / exposed	2 / 37 (5.41%)	1 / 14 (7.14%)	1 / 7 (14.29%)
occurrences all number	2	1	1
Rash pruritic
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin disorder
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Skin exfoliation
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin lesion
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	2
Urticaria
subjects affected / exposed	1 / 37 (2.70%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	1	1	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Anuria
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Dysuria
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Nephrolithiasis
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Oliguria
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Pelvi-ureteric obstruction
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Renal failure
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Hypothyroidism
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Secondary adrenocortical insufficiency
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 37 (5.41%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	2	1	0
Arthritis
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Back pain
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Bone pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Flank pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Growth failure
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hypertrophic osteoarthropathy
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Joint swelling
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Muscle spasms
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Osteonecrosis
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Osteopenia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Still's disease
subjects affected / exposed	0 / 37 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)
occurrences all number	0	2	0
Infections and infestations
Adenovirus infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	3	0	1
BK virus infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Bacillus bacteraemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Candida infection
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	2
Cestode infection
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Clostridium difficile infection
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	3	0	0
Croup infectious
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Cytomegalovirus chorioretinitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Cytomegalovirus infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Cytomegalovirus infection reactivation
subjects affected / exposed	5 / 37 (13.51%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	6	0	0
Enterobacter sepsis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Enterococcal bacteraemia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Enterovirus infection
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Epstein-Barr viraemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Epstein-Barr virus infection
subjects affected / exposed	1 / 37 (2.70%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	1	1	0
Escherichia bacteraemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Folliculitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastroenteritis adenovirus
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Gastroenteritis norovirus
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Gastroenteritis salmonella
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Herpes simplex gastritis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Human herpesvirus 6 infection reactivation
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Influenza
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Klebsiella bacteraemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Meningitis enterococcal
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Oesophageal candidiasis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Oral candidiasis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Gastroenteritis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Otitis externa
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Parainfluenzae virus infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Periorbital cellulitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Pharyngitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Pneumonia bacterial
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Pseudomonal sepsis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Rhinitis
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	2 / 7 (28.57%)
occurrences all number	3	0	3
Rhinovirus infection
subjects affected / exposed	1 / 37 (2.70%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	1	1	0
Serratia bacteraemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Sinusitis bacterial
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Skin bacterial infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Staphylococcal bacteraemia
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	8	0	0
Staphylococcal infection
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Tracheitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Tracheobronchitis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Upper respiratory tract infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Urinary tract infection
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Urinary tract infection bacterial
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Urinary tract infection viral
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Viral haemorrhagic cystitis
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Viral infection
subjects affected / exposed	0 / 37 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)
occurrences all number	0	1	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 37 (2.70%)	4 / 14 (28.57%)	1 / 7 (14.29%)
occurrences all number	1	5	2
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Fluid overload
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	4	0	0
Fluid retention
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hypercalcaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	1
Hypercreatininaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hyperglycaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Hypernatraemia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Hypoalbuminaemia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hypocalcaemia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	0	1
Hypokalaemia
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	2 / 7 (28.57%)
occurrences all number	4	0	2
Hypomagnesaemia
subjects affected / exposed	3 / 37 (8.11%)	0 / 14 (0.00%)	2 / 7 (28.57%)
occurrences all number	4	0	3
Hypophagia
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Hypophosphataemia
subjects affected / exposed	2 / 37 (5.41%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Malnutrition
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0
Metabolic acidosis
subjects affected / exposed	0 / 37 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	1
Milk soy protein intolerance
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0
Poor feeding infant
subjects affected / exposed	1 / 37 (2.70%)	0 / 14 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0

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Were there any global substantial amendments to the protocol? Yes

05 Dec 2013

United States, Version 2.0 - Modification to reflect increased frequency of visits pre- and post-HSCT; visits initially performed monthly basis were to be performed weekly - Addition of flexibility added to the visits to be performed - Addition of clarification regarding patients who, in the context of Study NI-0501-05, could continue receiving emapalumab beyond the 8 weeks foreseen in the Study NI-0501-04 protocol or in the NI-0501-CU protocol, including additional flexibility to be given in the assessment to be performed - Clarification that vaccinations were to be avoided until emapalumab was detected in serum and of what was not considered a protocol deviation - Addition of assessment of clinical response 1 month post-HSCT - Addition of consistency of visit description overall design section with explanations on how to adapt the SOA in the event conditioning and possibly the HSCT were performed before patient inclusion in Study NI-0501-05 - Addition of assessments to be performed, most of which were noninvasive - Addition of laboratory parameters of d-Dimers, gamma-glutamyl transferase, and lactate dehydrogenase and removal of proteinemia from safety laboratory assessments - Addition of evaluation for viral pathogens every 2 weeks as long as emapalumab was detectable in the serum - Addition of chest X-rays to detect tuberculosis at least every 3 weeks until 30 days post-HSCT and potentially at Day 60 post-HSCT, as long as emapalumab was detectable in the serum - Addition of text to Section 9.2, clarifying the potential risks linked to treatment applied only to patients receiving emapalumab during Study NI-0501-05 - Modification of Appendix A for patients still receiving NI-0501, to ensure transition from the on-drug to off-drug part of protocol was clear and accounted for variations in timing for conditioning and HSCT among patients - Modification of Appendix B, to clarify dosing regimen was responsibility of sponsor based on PK results

16 Dec 2013

Europe, Version 2.0 - Implementation of consistency with the US “twin” protocol to ensure patients in Europe had the same long-term follow-up monitoring as patients in the US and to allow for a combined analysis of the data generated by patients in Europe and the US - Implementation of recommendations made by the NI-0501-04 Scientific Steering Committee and Data Monitoring Committee based on the preliminary data assessment of the first patient enrolled - Modification of study design to increase the frequency of pre- and post-HSCT visits and implement flexibility to ensure assessments were adapted to patients’ condition and emapalumab concentrations detected - Modification of study design to account for patients whose conditioning and HSCT occurred during the short-term follow-up period for Study NI-0501-04 - Provide flexibility for the efficacy and safety assessments of patients who continued to receive emapalumab beyond Study NI-0501-04 - Clarification: that vaccinations were to be avoided until emapalumab concentration was detectable; surrounding what was not considered a protocol deviation; that stopping rules applied only to patients who continued receiving emapalumab - Addition of assessment of clinical response 1 month post-HSCT - Addition of a 1-week time-window for follow-up visits to be performed beyond 30 days post-HSCT - Specification that unplanned visits might occur to allow for additional assessments or treatment required - Modification of schedule of assessments (SOA) to ensure consistency with text of the protocol - Modification to risk analysis text to clarify potential risks linked to treatment applied only to patients still on treatment during Study NI-0501-05 - Modification of Appendix A, SOA for patients still receiving NI-0501, to be consistent with that in Study NI-0501-04 (version 3.0) - Modification of Appendix B, Investigational medicinal produce preparation and handling - Removal of Appendix E, NI-0501-04 protocol

16 Jan 2015

Europe, Version 2.1 - Update to Appendix A, SOA for patients still receiving NI-0501, to ensure consistency with text of protocol regarding recording of physical examination findings and vital sign measurements at each visit

11 Feb 2015

United States, Version 2.2 - Refer to the changes made under Europe amendment version 2.1, as the same modifications were made

26 Oct 2017

Europe, Version 3.0 - Addition of information regarding MAS to study rationale and update of studies included in clinical development program - Update of study objectives to include assessment of duration of response, post-HSCT outcome measures, background of disease activity, PD effects and the profile of relevant HLH biomarkers - Update to study design to expand the patient population to include subjects who participated in a previous emapalumab clinical study in which no long-term follow up was already planned and to state that patients having received emapalumab under the NI-0501-CU protocol could also be considered for enrollment whenever appropriate - Modification of the study design to remove details on the last visit performed and to remove the visits foreseen at the time of HSCT - Addition of details to study design for patients who underwent or were to undergo HSCT and for patients who whom HSCT was not planned - Update to inclusion criteria to include males with partner(s) of childbearing age must have agreed to take appropriate precautions to avoid pregnancy until 6 months after receipt of the last dose of emapalumab - Update to patient background and treatment care to clarify any treatment ongoing at the time of study entry was to be continued as deemed necessary by the Investigator and that patients receiving prophylactic treatments for infections at study entry were to continue therapy as long as emapalumab concentrations are detectable in serum - Clarification there was no restriction in the use of medications, except for live or attenuated-live vaccinations that were to be avoided as long as emapalumab concentrations were detectable in serum - Revision of study endpoints to clarify safety, efficacy, PK, PD, and immunogenicity assessments and to remove clinical response and survival from the monitoring of background disease activity - Removal of select laboratory parameters - Addition of serious criteria to AE assessment and clarification

31 Oct 2017

United States, Version 3.0 - Refer to the changes made under Europe amendment version 3.0, as the same modifications were made

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A multicentre study for the long-term follow-up of HLH patients who received treatment with NI-0501, an anti-interferon gamma monoclonal antibody

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Adverse Events

Primary: Number of Participants With Adverse Events

Secondary: Cumulative Duration of Response

Secondary: Cumulative Duration of Response

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Secondary: Overall Survival: Number of Participants Alive

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Secondary: Background Disease Activity: Macrophage Activation Syndrome in sHLH participants

Secondary: Background Disease Activity: Macrophage Activation Syndrome in sHLH participants

Secondary: Circulating Emapalumab Levels: Enrolled-04 Cohort

Secondary: Circulating Emapalumab Levels: Enrolled-04 Cohort

Secondary: Circulating Emapalumab Levels: Enrolled-06 Cohort

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Substantial protocol amendments (globally)

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Denmark
Estonia
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Greece
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Outside EU/EEA

Clinical trials

Clinical Trial Results: A multicentre study for the long-term follow-up of HLH patients who received treatment with NI-0501, an anti-interferon gamma monoclonal antibody

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Adverse Events

Primary: Number of Participants With Adverse Events

Secondary: Cumulative Duration of Response

Secondary: Cumulative Duration of Response

Secondary: Duration of First Response

Secondary: Duration of First Response

Secondary: Overall Survival: Number of Participants Alive

Secondary: Overall Survival: Number of Participants Alive

Secondary: Post-HSCT outcome indices

Secondary: Post-HSCT outcome indices

Secondary: Background Disease Activity: Macrophage Activation Syndrome in sHLH participants

Secondary: Background Disease Activity: Macrophage Activation Syndrome in sHLH participants

Secondary: Circulating Emapalumab Levels: Enrolled-04 Cohort

Secondary: Circulating Emapalumab Levels: Enrolled-04 Cohort

Secondary: Circulating Emapalumab Levels: Enrolled-06 Cohort

Secondary: Circulating Emapalumab Levels: Enrolled-06 Cohort

Secondary: Total Human Interferon Gamma Levels: Enrolled-04 Cohort

Secondary: Total Human Interferon Gamma Levels: Enrolled-04 Cohort

Secondary: Total Human Interferon Gamma Levels: Enrolled-06 Cohort

Secondary: Total Human Interferon Gamma Levels: Enrolled-06 Cohort

Secondary: Number of Participants with Antidrug Antibodies

Secondary: Number of Participants with Antidrug Antibodies

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A multicentre study for the long-term follow-up of HLH patients who received treatment with NI-0501, an anti-interferon gamma monoclonal antibody