A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)

• Sponsor: Swedish Orphan Biovitrum (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03311854
• Collaborator: (none)
• Enrollment: 14
• Locations: 5
• Arm: 1
• Actual Duration (Months): 26.9
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD). Emapalumab is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine which contributes to the inflammation and tissue damage seen in MAS. The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in sJIA or AOSD participants developing MAS, presenting an inadequate response to high dose glucocorticoid treatment.

Condition or Disease	Intervention/Treatment	Phase
Macrophage Activation Syndrome; Lymphohistiocytosis, Hemophagocytic; Arthritis, Juvenile; Adult Onset Still Disease	Drug: Emapalumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot, Open-label, Single Arm, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
• Actual Study Start Date: Feb 20, 2018
• Actual Primary Completion Date: May 19, 2020
• Actual Study Completion Date: May 19, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Emapalumab

Drug: Emapalumab; Emapalumab was administered at an initial dose of 6 mg/kg by intravenous infusion. Emapalumab treatment continued at a dose of 3 mg/kg, every 3 days until study day 15, and then twice-a-week for an additional 2 weeks, i.e., until study day 28. The emapalumab regimen could be adapted (the frequency between infusions shortened, the dose increased, or the treatment prolonged beyond 4 weeks) upon assessment of a favourable benefit-risk profile. There was a 4-week off-drug follow-up period (up to Week 8).; Other Names: Gamifant

Outcome Measures

Primary Outcome Measures

1. Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious) [Up to Week 8]

2. Evolution of Laboratory Parameters [Up to Week 8]

   Shifts from baseline in the following MAS-relevant laboratory parameters are reported: Leukocytes Platelets Lactate dehydrogenase (LDH) Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Ferritin C-reactive protein Activated partial thromboplastin time (aPTT) Prothrombin time D-dimer Fibrinogen

3. Number of Participants Withdrawn Due to Safety Reasons [Up to Week 8]

4. Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment [Week 8]

   Remission from MAS was evaluated according to the following criteria: Resolution of clinical signs and symptoms according to the investigator (MAS clinical signs and symptoms activity score ≤ 1) and Normalization of laboratory parameters relevant to MAS, as follows: WBC count and platelet count above the LLN. LDH below 1.5 × the ULN. ALT and AST both below 1.5 × the ULN. Fibrinogen higher than 100 mg/dL. Ferritin levels decreased by at least 80 % from values at screening or baseline (whichever was higher) or below 2000 ng/mL, whichever was lower.

5. Time to First MAS Remission [Up to Week 8]

6. Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study [Up to Week 8]

   Permanently tapering by at least 50% of the equivalent dose of prednisone. This was defined as achieving reduction of 50% of the baseline dose [SD0] and maintaining the reduction until the end of study).

7. Time to Achievement of Permanent Glucocorticoids Tapering [Up to Week 8]

   Time to achievement of permanent glucocorticoid tapering by at least 50% of the equivalent dose of prednisone administered at emapalumab treatment start.

8. Survival Time [Up to Week 8]

   Number of participants alive at the end of the study

9. Number of Participants Withdrawn From the Study Due to Lack of Efficacy [Up to Week 8]

   Number of participants withdrawn from the study due to lack of efficacy

10. Levels of Emapalumab Concentration [Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.]

    On all infusion days, PK samples were collected before the infusion start and between 15 and 30 minutes after infusion completion. In addition, following the first emapalumab infusion, PK samples were collected approximately 24 and 48 hours post-infusion, and following the second emapalumab infusion, PK samples were collected approximately 48 hours post-infusion. Upon treatment completion, PK samples were collected on all non-infusion visits until the 4-week follow-up visit/EOS.

11. Pharmacodynamic Parameters [Up to Week 8]

    Levels of total INF-gamma, CXCL9 and CXCL10

12. Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity [Up to Week 8]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 0 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients of both genders

• For sJIA patients: Confirmed sJIA diagnosis. For patients presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility. For AOSD patients: confirmed AOSD diagnosis as per Yamaguchi criteria.

• Diagnosis of active MAS.

• An inadequate response to high dose i.v. glucocorticoid treatment administered for at least 3 days as per local standard of care (including but not limited to pulses of 30 mg/kg PDN on 3 consecutive days). High dose i.v. glucocorticoid should not be lower than 2 mg/kg/day of PDN equivalent in 2 divided doses (or at least 60 mg/day in patients of 30 kg or more). In case of rapid worsening of the patient's condition and/or lab parameters, inclusion may occur within less than 3 days from starting high dose i.v. glucocorticoids.

• Tocilizumab, TNF inhibitors and canakinumab, if administered, have to be discontinued before emapalumab initiation.

• Having received guidance on contraception for both male and female patients sexually active and having reached puberty. Females of child-bearing potential require use of highly effective contraceptive measures. Males with partners(s) of child-bearing potential must agree to take appropriate precautions.

• Informed consent provided by the patient (as required by local law), or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable.

Exclusion Criteria:

• Diagnosis of suspected or confirmed primary HLH or HLH consequent to a neoplastic disease.

• Active mycobacteria (typical and atypical), Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.

• Clinical suspicion of latent tuberculosis.

• Positive serology for HIV antibodies.

• Presence of malignancy.

• Patients who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, CNS, liver or renal function that in the opinion of the Investigator may significantly affect likelihood to respond to treatment and/or assessment of emapalumab safety.

• History of hypersensitivity or allergy to any component of the study drug

• Receipt of a BCG vaccine within 12 weeks prior to screening.

• Receipt of live or attenuated live vaccines (other than BCG) within 6 weeks prior to screening.

• Pregnant or lactating female patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children'S Hospital	Cincinnati	Ohio	United States	45229
2	Hôpital Necker-Enfants Malades, Unité d'Immunologie-hématologie et Rhumatologie pédiatriques	Paris		France	75743
3	IRCCS Ospedale Pediatrico, Bambino Gesù	Rome		Italy	00165
4	Hospital Sant Joan de Deu	Barcelona		Spain	08950
5	Great Ormond Street Hospital for Children	London		United Kingdom	WC1N 3JH

Sponsors and Collaborators

• Swedish Orphan Biovitrum

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 7, 2020
• Statistical Analysis Plan - Apr 22, 2021

More Information

Publications

None provided.

• Responsible Party: Swedish Orphan Biovitrum
• ClinicalTrials.gov Identifier: NCT03311854
• Other Study ID Numbers: NI-0501-06
• First Posted: Oct 17, 2017
• Last Update Posted: May 17, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Swedish Orphan Biovitrum: Emapalumab; Gamifant; Macrophage activation syndrome; Secondary hemophagocytic lymphohistiocytosis; Interferon-gamma; Systemic juvenile idiopathic arthritis; Adult-onset Still's disease; MAS; HLH; sHLH; IFN-gamma; IFNγ; sJIA; AOSD; NI-0501-06; NI-0501
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Still's Disease, Adult-Onset; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Syndrome

Study Results

Participant Flow

Arm/Group Title	All Treated Population
Arm/Group Description	Of the 16 patients who were screened for the study, 14 were enrolled. All 14 patients completed the study; no patient was withdrawn after the start of treatment. All 14 patients received emapalumab and were included in the all treated population.
Period Title: Overall Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Enrolled Participants
Arm/Group Description	Baseline data are provided for all participants who were enrolled in the study.
Overall Participants	14
Age (Count of Participants)
<=18 years	13 92.9%
Between 18 and 65 years	1 7.1%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.9 (6.6)
Sex: Female, Male (Count of Participants)
Female	10 71.4%
Male	4 28.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 14.3%
White	11 78.6%
More than one race	0 0%
Unknown or Not Reported	1 7.1%
Region of Enrollment (Count of Participants)
United States	3 21.4%
Italy	7 50%
United Kingdom	2 14.3%
Spain	1 7.1%
France	1 7.1%

Outcome Measures

1. Primary Outcome

Title	Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious)
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Number of participants with a TEAE	13 92.9%
Number of participants with a serious TEAE	6 42.9%
Number of participants with a severe TEAE	2 14.3%
Number of participants with a moderate TEAE	10 71.4%
Number of participants with a mild TEAE	13 92.9%
Number of participants with a TEAE related to emapalumab	4 28.6%
Number of participants with a TEAE unrelated to emapalumab	13 92.9%
Number of participants with a TEAE with an outcome of recovered/resolved	13 92.9%
Number of participants with a TEAE with an outcome of not recovered/not resolved	3 21.4%
Number of participants with a TEAE with an outcome of recovering/resolving	1 7.1%
Number of participants with a TEAE with an outcome of unknown	1 7.1%

2. Primary Outcome

Title	Evolution of Laboratory Parameters
Description	Shifts from baseline in the following MAS-relevant laboratory parameters are reported: Leukocytes Platelets Lactate dehydrogenase (LDH) Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Ferritin C-reactive protein Activated partial thromboplastin time (aPTT) Prothrombin time D-dimer Fibrinogen
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Leukocytes: From a high value at baseline to a value within the reference range at Week 8	2 14.3%
Leukocytes: From a low value at baseline to a value within the reference range at Week 8	4 28.6%
Leukocytes: From a low value at baseline to a high value at Week 8	2 14.3%
Platelets: From a high value at baseline to a value within the reference range at Week 8	1 7.1%
Platelets: From a low value at baseline to a value within the reference range at Week 8	6 42.9%
Platelets: From a low value at baseline to a high value at Week 8	3 21.4%
LDH: From a high value at baseline to a value within the reference range at Week 8	6 42.9%
ALT: From a high value at baseline to a value within the reference range at Week 8	10 71.4%
ALT: From a high value at baseline to a low value at Week 8	1 7.1%
AST: From a high value at baseline to a value within the reference range at Week 8	11 78.6%
Ferritin: From a high value at baseline to a value within the reference range at Week 8	11 78.6%
Ferritin: From a high value at baseline to a low value at Week 8	2 14.3%
C-reactive protein: From a high value at baseline to a value within the reference range at Week 8	9 64.3%
aPTT: From a high value at baseline to a value within the reference range at Week 8	1 7.1%
aPTT: From a high value at baseline to a low value at Week 8	1 7.1%
aPTT: From a value within the reference range at baseline to a low value at Week 8	3 21.4%
aPTT: From a low value at baseline to a value within the reference range at Week 8	1 7.1%
aPTT: From a low value at baseline to a high value at Week 8	1 7.1%
Prothrombin time: From a high value at baseline to a value within the reference range at Week 8	5 35.7%
Prothrombin time: From a high value at baseline to a low value at Week 8	1 7.1%
Prothrombin time: From a value within the reference range at baseline to a low value at Week 8	3 21.4%
Prothrombin time: From a low value at baseline to a value within the reference range at Week 8	1 7.1%
D-dimer: From a high value at baseline to a value within the reference range at Week 8	8 57.1%
Fibrinogen: From a high value at baseline to a value within the reference range at Week 8	1 7.1%
Fibrinogen: From a value within the reference range at baseline to a high value at Week 8	1 7.1%
Fibrinogen: From a low value at baseline to a value within the reference range at Week 8	5 35.7%
Fibrinogen: From a low value at baseline to a high value at Week 8	1 7.1%

3. Primary Outcome

Title	Number of Participants Withdrawn Due to Safety Reasons
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	0 0%

4. Primary Outcome

Title	Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment
Description	Remission from MAS was evaluated according to the following criteria: Resolution of clinical signs and symptoms according to the investigator (MAS clinical signs and symptoms activity score ≤ 1) and Normalization of laboratory parameters relevant to MAS, as follows: WBC count and platelet count above the LLN. LDH below 1.5 × the ULN. ALT and AST both below 1.5 × the ULN. Fibrinogen higher than 100 mg/dL. Ferritin levels decreased by at least 80 % from values at screening or baseline (whichever was higher) or below 2000 ng/mL, whichever was lower.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	11 78.6%

5. Primary Outcome

Title	Time to First MAS Remission
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Median (95% Confidence Interval) [days]	25

6. Primary Outcome

Title	Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study
Description	Permanently tapering by at least 50% of the equivalent dose of prednisone. This was defined as achieving reduction of 50% of the baseline dose [SD0] and maintaining the reduction until the end of study).
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	12 85.7%

7. Primary Outcome

Title	Time to Achievement of Permanent Glucocorticoids Tapering
Description	Time to achievement of permanent glucocorticoid tapering by at least 50% of the equivalent dose of prednisone administered at emapalumab treatment start.
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Median (95% Confidence Interval) [days]	14.5

8. Primary Outcome

Title	Survival Time
Description	Number of participants alive at the end of the study
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	14 100%

9. Primary Outcome

Title	Number of Participants Withdrawn From the Study Due to Lack of Efficacy
Description	Number of participants withdrawn from the study due to lack of efficacy
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	0 0%

10. Primary Outcome

Title	Levels of Emapalumab Concentration
Description	On all infusion days, PK samples were collected before the infusion start and between 15 and 30 minutes after infusion completion. In addition, following the first emapalumab infusion, PK samples were collected approximately 24 and 48 hours post-infusion, and following the second emapalumab infusion, PK samples were collected approximately 48 hours post-infusion. Upon treatment completion, PK samples were collected on all non-infusion visits until the 4-week follow-up visit/EOS.
Time Frame	Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.

Outcome Measure Data

Analysis Population Description

Emapalumab concentrations were below the detection limit for all patients at SD0, except for Patient 501-001, in whom the emapalumab concentration (pre-dose) was 62108.4 μg/L. It should be noted that on SD1, the measurement results of emapalumab were below the detection limit for Patient 501-001, so it could not be ruled out that the samples from SD0 and SD1 for this patient were interchanged.

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab. Note: the Week 4 Visit 2 (post-dose) emapalumab concentration levels were based on 7 participants.
Measure Participants	14
Study Day 0 (pre-dose)	5455.444 (19985.0660)
Study Day 0 (post-dose)	104740.254 (20994.1054)
Week 4 Visit 2 (pre-dose)	115472.076 (58676.7953)
Week 4 Visit 2 (post-dose)	212900.657 (87466.3031)
4-week follow-up Visit/EoS	46447.462 (33657.0174)

11. Primary Outcome

Title	Pharmacodynamic Parameters
Description	Levels of total INF-gamma, CXCL9 and CXCL10
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population: Study Day 0	All Treated Population: 4-week Follow-up Visit/EoS
Arm/Group Description	Levels measured pre-dose on Study Day 0 in participants in the all treated population which included all patients who received any part of an infusion of emapalumab.	Levels measured at the 4-week follow-up visit/EoS in participants in the all treated population which included all patients who received any part of an infusion of emapalumab.
Measure Participants	14	14
CXCL9	21986.010 (29405.8787)	255.654 (596.4149)
CXCL10	7935.418 (9115.2857)	639.102 (1058.9589)
Total IFN-γ	425.528 (1191.8391)	2132.656 (2967.4920)

12. Primary Outcome

Title	Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
Description	The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
Time Frame	Up to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
Measure Participants	14
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Adverse events were recorded in patients from Study Day 0 (the day of the first emapalumab administration), during emapalumab treatment, and up to and including the 4-week follow-up visit/end of study (a minimum duration of 56 days). All adverse events were followed up for outcome at end of study; all serious adverse events were followed up until resolution.
Adverse Event Reporting Description	While all adverse events reported by the participants or their relatives or observed by the Investigator or their staff during the clinical study from the signature of the informed consent form up to and including the end-of-study visit were recorded, only treatment-emergent adverse events (those that occurred after the start of the first emapalumab administration) are reported here.
Arm/Group Title	All Treated Population
Arm/Group Description	The all treated population included all patients who received any part of an infusion of emapalumab.
All Cause Mortality
	All Treated Population
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	All Treated Population
	Affected / at Risk (%)	# Events
Total	6/14 (42.9%)
Blood and lymphatic system disorders
Thrombocytopenia	1/14 (7.1%)	1
Cardiac disorders
Cardiopulmonary failure	1/14 (7.1%)	1
Intracardiac thrombus	1/14 (7.1%)	1
Pericarditis	1/14 (7.1%)	1
Gastrointestinal disorders
Pneumatosis intestinalis	1/14 (7.1%)	1
Infections and infestations
Cytomegalovirus infection reactivation	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Still's disease	1/14 (7.1%)	1
Nervous system disorders
Juvenile myoclonic epilepsy	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Rash	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	All Treated Population
	Affected / at Risk (%)	# Events
Total	13/14 (92.9%)
Blood and lymphatic system disorders
Leukopenia	1/14 (7.1%)	1
Neutropenia	1/14 (7.1%)	1
Thrombocytopenia	1/14 (7.1%)	1
Cardiac disorders
Cardiopulmonary failure	1/14 (7.1%)	1
Intracardiac thrombus	1/14 (7.1%)	1
Pericarditis	1/14 (7.1%)	1
Sinus bradycardia	1/14 (7.1%)	1
Tachycardia	1/14 (7.1%)	1
Ear and labyrinth disorders
Tympanic membrane hyperaemia	1/14 (7.1%)	1
Eye disorders
Eye oedema	1/14 (7.1%)	1
Eye pruritus	1/14 (7.1%)	1
Gastrointestinal disorders
Diarrhoea	3/14 (21.4%)	4
Abdominal pain	1/14 (7.1%)	1
Abdominal pain upper	1/14 (7.1%)	1
Nausea	1/14 (7.1%)	1
Pneumatosis intestinalis	1/14 (7.1%)	1
General disorders
Injection site reaction	2/14 (14.3%)	2
Catheter site thrombosis	1/14 (7.1%)	1
Chest pain	1/14 (7.1%)	1
Condition aggravated	1/14 (7.1%)	1
Pyrexia	1/14 (7.1%)	4
Secretion discharge	1/14 (7.1%)	1
Hepatobiliary disorders
Cholelithiasis	1/14 (7.1%)	1
Hepatic steatosis	1/14 (7.1%)	1
Immune system disorders
Drug hypersensitivity	1/14 (7.1%)	1
Infections and infestations
Cytomegalovirus infection reactivation	3/14 (21.4%)	3
Cytomegalovirus infection	1/14 (7.1%)	1
Nasopharyngitis	1/14 (7.1%)	1
Viral infection	1/14 (7.1%)	1
Injury, poisoning and procedural complications
Allergic transfusion reaction	1/14 (7.1%)	1
Contusion	1/14 (7.1%)	1
Infusion related reaction	1/14 (7.1%)	1
Investigations
Adenovirus test positive	1/14 (7.1%)	1
BK polyomavirus test positive	1/14 (7.1%)	1
Body temperature increased	1/14 (7.1%)	1
Cytomegalovirus test positive	1/14 (7.1%)	1
Respirovirus test positive	1/14 (7.1%)	1
Metabolism and nutrition disorders
Hyperglycaemia	3/14 (21.4%)	3
Hyperkalaemia	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Still's disease	1/14 (7.1%)	1
Tenosynovitis	1/14 (7.1%)	1
Nervous system disorders
Headache	2/14 (14.3%)	4
Axonal neuropathy	1/14 (7.1%)	1
Juvenile myoclonic epilepsy	1/14 (7.1%)	1
Lethargy	1/14 (7.1%)	1
Peripheral sensorimotor neuropathy	1/14 (7.1%)	1
Seizure	1/14 (7.1%)	1
Psychiatric disorders
Anxiety	1/14 (7.1%)	1
Confusional state	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/14 (7.1%)	2
Dyspnoea	1/14 (7.1%)	1
Epistaxis	1/14 (7.1%)	3
Pharyngeal erythema	1/14 (7.1%)	2
Pleural effusion	1/14 (7.1%)	1
Tachypnoea	1/14 (7.1%)	1
Skin and subcutaneous tissue disorders
Rash	4/14 (28.6%)	4
Acanthosis nigricans	1/14 (7.1%)	1
Dermatitis diaper	1/14 (7.1%)	1
Dry skin	1/14 (7.1%)	1
Rash erythematous	1/14 (7.1%)	1
Rash maculo-papular	1/14 (7.1%)	1
Rash pruritic	1/14 (7.1%)	1
Skin ulcer	1/14 (7.1%)	1
Vascular disorders
Hypertension	3/14 (21.4%)	3
Thrombophlebitis superficial	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.