GRAVITAS-301: A Study of Itacitinib or Placebo in Combination With Corticosteroids for Treatment of Acute Graft-Versus-Host Disease

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03139604
• Collaborator: (none)
• Enrollment: 439
• Locations: 129
• Arms: 2
• Actual Duration (Months): 35.8
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate itacitinib or placebo in combination with corticosteroids as first-line treatment of participants with Grade II to IV acute graft-versus-host disease (aGVHD).

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease (GVHD)	Drug: Itacitinib; Drug: Placebo; Drug: Prednisone; Drug: Methylprednisolone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 439 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: GRAVITAS-301: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease
• Actual Study Start Date: Jul 19, 2017
• Actual Primary Completion Date: May 2, 2019
• Actual Study Completion Date: Jul 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Itacitinib Itacitinib plus corticosteroids	Drug: Itacitinib; Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids.; Other Names: INCB039110 ; Drug: Prednisone; Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.; Other Names: Deltasone Prednicot predniSONE Intensol Rayos Sterapred Sterapred DS ; Drug: Methylprednisolone; Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.; Other Names: Medrol Medrol Dosepak Solu-Medrol
Placebo Comparator: Placebo Matching placebo plus corticosteroids	Drug: Placebo; Matching placebo tablets administered orally once daily (QD) plus corticosteroids.; Drug: Prednisone; Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day.; Other Names: Deltasone Prednicot predniSONE Intensol Rayos Sterapred Sterapred DS ; Drug: Methylprednisolone; Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment.; Other Names: Medrol Medrol Dosepak Solu-Medrol

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index [Day 28]

   Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).

Secondary Outcome Measures

1. Nonrelapse Mortality [Month 6,9,12 and 24]

   Defined as the percentage of participants who died due to causes other than malignancy relapse.

2. Duration of Response [Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months]

   Defined as the interval from first response until GVHD progression or death.

3. Cmax of Itacitinib When Administered in Combination With Corticosteroids [Protocol-defined timepoints up to Day 28]

   Defined as maximum observed plasma concentration.

4. Cmin of Itacitinib When Administered in Combination With Corticosteroids [Protocol-defined timepoints up to Day 28]

   Defined as minimum observed plasma concentration.

5. Tmax of Itacitinib When Administered in Combination With Corticosteroids [Protocol-defined timepoints up to Day 28]

   Defined as time to maximum plasma concentration.

6. AUC of Itacitinib When Administered in Combination With Corticosteroids [Protocol-defined timepoints up to Day 28]

   Defined as area under the concentration-time curve.

7. CL/F of Itacitinib When Administered in Combination With Corticosteroids [Protocol-defined timepoints up to Day 28]

   Defined as oral dose clearance.

8. Time to Response [End of Study, total particpation expected to average 24 months]

   Defined as the interval from treatment initiation to first response

9. Relapse Rate of Malignant and Nonmalignant Hematologic Disease [Randomization through end of Study, study duration expected to average 24 months]

   Defined as the proportion of subjects whose underlying hematologic disease relapses

10. Malignancy Relapse-related Mortality Rate [Randomization through end of Study, study duration expected to average 24 months]

    Defined as the proportion of subjects whose malignancy relapses and has a fatal outcome.

11. Failure-free Survival [6 months from randomization]

    Defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD)

12. Overall Survival (OS) [End of Study up to approximately 24 months]

    Defined as the interval from study enrollment to death due to any cause.

13. Number of Treatment-emergent Adverse Events With INCB39110 [30-35 days after end of treatment, approximately 24 months]

    Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment

14. Incidence Rate of Secondary Graft Failure [Randomization through end of Study, study duration expected to average 24 months]

    Defined as > 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (< 0.5 × 109/L) and/or thrombocytopenia (< 20 × 109/L) within 2 months of transplantion

15. Proportion of Subjects Who Discontinue Corticosteroids [Days 28, 56, 100, and 180]

    Average and cumulative corticosteroid dose usage will be calculated and proportion of subjects discontinuing corticosteroids will be tabulated

16. Proportion of Subjects Who Discontinue Immunosuppressive Medications [Days 56 and 100]

    Summary statistics of subjects discontinuing immunosuppressive medications will be calculated

17. Incidence Rate of aGVHD Flares [up to day 100]

18. Incidence Rate of cGVHD [Days 180 and 365]

19. Objective Response Rate [Days 14, 56 and 100]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.

• Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen.

• Evidence of myeloid engraftment. Use of growth factor supplementation is allowed.

• Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min measured or calculated by Cockroft Gault equation.

• Willing to avoid pregnancy or fathering children.

• Able to give written informed consent and comply with all study visits and procedures.

• Able to swallow and retain oral medication.

Exclusion Criteria:

• Has received more than 1 allo-HSCT.

• Has received more than 2 days of systemic corticosteroids for aGVHD.

• Presence of GVHD overlap syndrome.

• Presence of an active uncontrolled infection.

• Known human immunodeficiency virus infection.

• Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation.

• Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.

• Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.

• Severe organ dysfunction unrelated to underlying GVHD, including:

• Cholestatic disorders or unresolved veno-occlusive disease of the liver.

• Clinically significant or uncontrolled cardiac disease.

• Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.

• Currently breast feeding.

• Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.

• Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.

• Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego (UCSD) - Moores Cancer Center	La Jolla	California	United States	92093-0698
2	University of Southern California	Los Angeles	California	United States	90033
3	University of California, Los Angeles (UCLA) - Medical Center	Los Angeles	California	United States	90095-1678
4	Stanford Cancer Center	Stanford	California	United States	94305
5	University of Colorado - Aurora Cancer Center	Aurora	Colorado	United States	80045
6	University of Florida (UF) - Division of Hematology & Oncology	Gainesville	Florida	United States	32610
7	University of Miami - Sylvester Cancer Center	Miami	Florida	United States	33136
8	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
9	University of Illinois at Chicago	Chicago	Illinois	United States	60612
10	University of Chicago	Chicago	Illinois	United States	60637
11	Advocate Lutheran General Hospital - Oncology Specialists SC	Park Ridge	Illinois	United States	60028
12	Indiana University (IU) Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
13	Indiana Blood and Marrow Transplant	Indianapolis	Indiana	United States	46237
14	University of Iowa	Iowa City	Iowa	United States	52242
15	University of Kansas Cancer Center	Westwood	Kansas	United States	66205
16	Tulane University Medical Center	New Orleans	Louisiana	United States	70112
17	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
18	Tufts Medical Center	Boston	Massachusetts	United States	02111
19	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
20	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
21	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
22	University of Michigan	Ann Arbor	Michigan	United States	48109
23	Henry Ford Hospital	Detroit	Michigan	United States	48202
24	Spectrum Health	Grand Rapids	Michigan	United States	49503
25	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
26	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
27	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
28	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
29	John Theurer Cancer Center At Hackensack UMC	Hackensack	New Jersey	United States	07601
30	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903-2681
31	Northwell Health	Lake Success	New York	United States	11042
32	Columbia University	New York	New York	United States	10032
33	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
34	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
35	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
36	Wake Forest Baptist Medical Center - Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
37	Oncology Hematology in Cincinnati	Cincinnati	Ohio	United States	45236
38	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
39	The Ohio State University (OSU)	Columbus	Ohio	United States	43210
40	University of Oklahoma - Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
41	Oregon Health & Science University (OHSU)	Portland	Oregon	United States	97239-3098
42	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
43	University of Pittsburgh Medical Center (UPMC) - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
44	Greenville Health System	Greenville	South Carolina	United States	29615
45	Methodist Healthcare Foundation	Memphis	Tennessee	United States	38104
46	Sarah Cannon Research Institute, LLC (SCRI)	Nashville	Tennessee	United States	37203
47	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
48	Texas Transplant Institute	San Antonio	Texas	United States	78229
49	University of Virginia Medical Center	Charlottesville	Virginia	United States	22908
50	St Vincents Hospital Sydney Limited	Darlinghurst		Australia	NSW 2010
51	Ordensklinikum Linz GmbH Elisabethinen	Linz		Austria	4020
52	ZNA Stuivenberg	Antwerpen		Belgium	2060
53	General Hospital Sint-Jan Brugge-Oostend	Brugge		Belgium	8000
54	Institut Jules Bordet	Brussels		Belgium	1000
55	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
56	Universitair Ziekenhuis Gent (UZG)	Gent		Belgium	9000
57	Jessa Ziekenhuis	Hasselt		Belgium	3500
58	Hopital universitaire du Sart Tilman de Liege	Liege 1		Belgium	4000
59	AZ Delta	Roeselare		Belgium	8800
60	UHKT Prague - Institute of Hematology and Blood Transfusion	Praha 2		Czechia	128 20
61	Helsinki University Central Hospital	Helsinki		Finland	00290
62	CHU Amiens Picardie - Hopital Sud	Amiens		France	80054
63	CHRU de Lille-Hopital Claude Huriez	LILLE Cedex		France	59037
64	Hotel Dieu Hospital - Hematologie	Nantes		France	44000
65	Hopital Saint Louis	Paris		France	75010
66	Hopital Haut Leveque - CHU Bordeaux - Maladies du sang	Pessac		France	33604
67	Hopital de Hautepierre	Strasbourg cedex		France	67098
68	Institut Claudius Regaud-Universitaire du Cancer Toulouse Oncopol	Toulouse Cedex 9		France	31059
69	CHU de Nancy	Vandoeuvre les Nancy		France	54500
70	University Clinic Carl Gustav Carus, Technical University Dresden	Dresden		Germany	1307
71	Universitatsklinikum Freiburg - Klinik fur Innere Medizin I	Freiburg		Germany	79106
72	Universitatsklinikum Hamburg - Eppendorf	Hamburg		Germany	20246
73	Universitaet zu Koln - Universitaetsklinikum Koeln (Uniklinik Koeln)	Köln		Germany	50924
74	Universitaetsklinikum Leipzig	Leipzig		Germany	4103
75	Universitaetsmedizin der Johannes Gutenberg	Mainz		Germany	55131
76	UKGM Marburg Innere Medizin: Haematologie Onkolog	Marburg		Germany	35043
77	General Hospital of Thessaloniki G. Papanikolaou - Hematology Department	Chortiátis		Greece	57010
78	Rambam Health Care Campus	Haifa		Israel	3109601
79	Hadassah Hebrew University Medical Center Ein Karem	Jerusalem		Israel	9112001
80	Chaim Sheba Medical Center	Ramat Gan		Israel	5262160
81	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	6423906
82	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo		Italy	24127
83	C.T.M.O. Ospedale Roberto Binaghi ATS Cagliari	Cagliari		Italy	09126
84	Azienda Ospedaliero Universitaria (AOU) Policlinico - Vittorio Emanuele - Presidio Ospedaliero Ferrarotto Alessi	Catania		Italy	95124
85	Azienda Ospedaliero Universitaria Careggi	Firenze		Italy	50134
86	ASST Grande Ospedale Metropolitano Niguarda	Milano		Italy	20162
87	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano	Milan		Italy	20122
88	IRCCS Ospedale San Raffaele	Milan		Italy	20132
89	Clinica Ematologica CTA, Ospedale "San Gerardo" di Monza	Monza		Italy	20900
90	Casa di Cura La Maddalena	Palermo		Italy	90146
91	Fondazione IRCCS Policlinco San Matteo	Pavia		Italy	27100
92	Presidio Ospedaliero Pescara	Pescara		Italy	65124
93	Azienda Ospedaliera Bianchi-Melacrino-Morelli Ospedali Riuniti	Reggio Calabria		Italy	89124
94	Azienda Unità Sanitaria Locale di Reggio Emilia	Reggio Emilia		Italy	42123
95	University of Rome La Sapienza	Roma		Italy	00161
96	Istituto Clinico Humanitas	Rozzano		Italy	20089
97	A.O.U. Città della Salute e della Scienza di Torino	Torino		Italy	10126
98	SOC Clinica Ematologica, Azienda Ospediero-Universitaria di Udine	Udine		Italy	33100
99	Seoul National University Hospital	Seoul		Korea, Republic of	3080
100	Auckland District Health Board	Auckland		New Zealand	1023
101	Centrum Onkologii- Instytut w Gliwicach	Gliwice		Poland	44-101
102	Klinika Transplantacji Komorek Krwiotworczych - Instytut Hematologii i Transfuzjologii	Warsaw		Poland	02-776
103	Instituto Portugues de Oncologia de Lisboa Francisco Gentil EPE (IPO-Lisboa)	Lisboa		Portugal	1099-023
104	Centro Hospitalar Lisboa Norte - Hospital de Santa Maria	Lisboa		Portugal	1649-035
105	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto		Portugal	4200-072
106	Hospital de la Santa Creu i Sant Pau - Servei de Hematologia Clinica	Barcelona		Spain	08025
107	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
108	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain	08036
109	Instituto Catalan de Oncologia - Hospital Duran i Reynals	Barcelona		Spain	08907
110	Complejo Hospitalario Universitario de Granada - Hospital Universitario Virgen de las Nieves	Granada		Spain	18014
111	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
112	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
113	Hospital Universitario La Paz	Madrid		Spain	28046
114	Hospital Universitario Puerta de Hierro Majadahonda	Madrid		Spain	28222
115	Hospital Universitario de Salamanca	Salamanca		Spain	37007
116	Hospital Universitario de Donostia	San Sebastián		Spain	20014
117	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
118	Hospital Clinico de Santiago de Compostela	Santiago de Compostela		Spain	15706
119	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
120	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
121	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
122	Universtity Hospital Basel - Haematology	Basel		Switzerland	4031
123	Hopitaux Universitaires de Geneve	Geneve		Switzerland	1211
124	Universitaetsspital Zuerich - Klinik fuer Haematology	Zuerich		Switzerland	CH-8091
125	China Medical University Hospital	Taichung		Taiwan	40447 ROC
126	Addenbrooke's Hospital	Cambridge		United Kingdom	CB2 0QQ
127	University Hospital of Wales	Cardiff		United Kingdom	CF14 4XW
128	Hammersmith Hospital	London		United Kingdom	W12 0HS
129	Nottingham University Hospitals	Nottingham		United Kingdom	NG5 1PB

Sponsors and Collaborators

• Incyte Corporation

Investigators

• Study Director: Rodica Morariu-Zamfir, MD, Incyte Corporation

Study Documents (Full-Text)

• Study Protocol - Aug 13, 2018
• Statistical Analysis Plan - Jul 23, 2019

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03139604
• Other Study ID Numbers: INCB 39110-301
• First Posted: May 4, 2017
• Last Update Posted: Aug 11, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Acute graft-versus-host disease; Janus kinase (JAK) inhibitor; itacitinib; corticosteroids; allogeneic hematopoietic stem cell transplant (allo-HSCT)
• Additional relevant MeSH terms: Graft vs Host Disease; Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 128 investigative sites in 19 different countries.
Pre-assignment Detail	A total of 498 participants were screened for this study, of which 59 participants were screen failures and 439 participants were randomized to treatment.

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Period Title: Overall Study
STARTED	219	220
COMPLETED	0	0
NOT COMPLETED	219	220

Baseline Characteristics

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids	Total
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Total of all reporting groups
Overall Participants	219	220	439
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.6 (13.53)	54.0 (12.96)	53.8 (13.23)
Sex: Female, Male (Count of Participants)
Female	82 37.4%	91 41.4%	173 39.4%
Male	137 62.6%	129 58.6%	266 60.6%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	17 7.8%	22 10%	39 8.9%
Not Hispanic or Latino	167 76.3%	169 76.8%	336 76.5%
Not Reported	17 7.8%	14 6.4%	31 7.1%
Unknown	12 5.5%	9 4.1%	21 4.8%
Other	6 2.7%	5 2.3%	11 2.5%
Missing	0 0%	1 0.5%	1 0.2%
Race/Ethnicity, Customized (Number) [Number]
White/Caucasian	196 89.5%	194 88.2%	390 88.8%
Black/African-American	8 3.7%	5 2.3%	13 3%
Asian	4 1.8%	4 1.8%	8 1.8%
American-Indian/Alaska Native	0 0%	2 0.9%	2 0.5%
Other	10 4.6%	11 5%	21 4.8%
Missing	1 0.5%	4 1.8%	5 1.1%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index
Description	Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Number (95% Confidence Interval) [Percentage of Participants]	74.0 33.8%	66.4 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Itacitinib Plus Corticosteroids, Placebo Plus Corticosteroids
	Comments	binomial distribution
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0782
	Comments	Not adjusted for multiplicity with interim and final analyses
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.959 to 2.204
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Nonrelapse Mortality
Description	Defined as the percentage of participants who died due to causes other than malignancy relapse.
Time Frame	Month 6,9,12 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
6 Months	36 16.4%	37 16.8%
9 Months	46 21%	45 20.5%
12 Months	51 23.3%	52 23.6%
24 Months	56 25.6%	52 23.6%

3. Secondary Outcome

Title	Duration of Response
Description	Defined as the interval from first response until GVHD progression or death.
Time Frame	Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Median (95% Confidence Interval) [days]	587	NA

4. Secondary Outcome

Title	Cmax of Itacitinib When Administered in Combination With Corticosteroids
Description	Defined as maximum observed plasma concentration.
Time Frame	Protocol-defined timepoints up to Day 28

Outcome Measure Data

Analysis Population Description

All subjects who receive at least 1 dose of study drug and provide at least 1 plasma sample after study drug administration will be considered as potential PK evaluable subjects. The data presented is from Day 7.

Arm/Group Title	Itacitinib Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	162
Mean (Standard Deviation) [nM]	796 (642)

5. Secondary Outcome

Title	Cmin of Itacitinib When Administered in Combination With Corticosteroids
Description	Defined as minimum observed plasma concentration.
Time Frame	Protocol-defined timepoints up to Day 28

Outcome Measure Data

Analysis Population Description

All subjects who receive at least 1 dose of study drug and provide at least 1 plasma sample after study drug administration will be considered as potential PK evaluable subjects. The data presented is from Day 7 as this is more representative of true steady state. Day 28 is positively biased as non responders are withdrawn from study by D28.

Arm/Group Title	Itacitinib Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	62
Mean (Standard Deviation) [nM]	72.5 (121)

6. Secondary Outcome

Title	Tmax of Itacitinib When Administered in Combination With Corticosteroids
Description	Defined as time to maximum plasma concentration.
Time Frame	Protocol-defined timepoints up to Day 28

Outcome Measure Data

Analysis Population Description

All subjects who receive at least 1 dose of study drug and provide at least 1 plasma sample after study drug administration will be considered as potential PK evaluable subjects. The data presented is from Day 7.

Arm/Group Title	Itacitinib Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	62
Median (Full Range) [hrs]	2.1

7. Secondary Outcome

Title	AUC of Itacitinib When Administered in Combination With Corticosteroids
Description	Defined as area under the concentration-time curve.
Time Frame	Protocol-defined timepoints up to Day 28

Outcome Measure Data

Analysis Population Description

All subjects who receive at least 1 dose of study drug and provide at least 1 plasma sample after study drug administration will be considered as potential PK evaluable subjects. The data presented is from Day 7.

Arm/Group Title	Itacitinib Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	62
Mean (Standard Deviation) [nM*h]	6720 (6210)

8. Secondary Outcome

Title	CL/F of Itacitinib When Administered in Combination With Corticosteroids
Description	Defined as oral dose clearance.
Time Frame	Protocol-defined timepoints up to Day 28

Outcome Measure Data

Analysis Population Description

All subjects who receive at least 1 dose of study drug and provide at least 1 plasma sample after study drug administration will be considered as potential PK evaluable subjects. The data presented is from Day 7.

Arm/Group Title	Itacitinib Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	62
Mean (Standard Deviation) [L/h]	104 (76.7)

9. Secondary Outcome

Title	Time to Response
Description	Defined as the interval from treatment initiation to first response
Time Frame	End of Study, total particpation expected to average 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population who were responders

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	195	185
Mean (Standard Deviation) [days]	9.9 (6.25)	10.1 (5.37)

10. Secondary Outcome

Title	Relapse Rate of Malignant and Nonmalignant Hematologic Disease
Description	Defined as the proportion of subjects whose underlying hematologic disease relapses
Time Frame	Randomization through end of Study, study duration expected to average 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	217	220
Number [percentage]	12.4	11.4

11. Secondary Outcome

Title	Malignancy Relapse-related Mortality Rate
Description	Defined as the proportion of subjects whose malignancy relapses and has a fatal outcome.
Time Frame	Randomization through end of Study, study duration expected to average 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Number [percentage]	6.4	7.7

12. Secondary Outcome

Title	Failure-free Survival
Description	Defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD)
Time Frame	6 months from randomization

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Number [proportion of participants]	44.29 20.2%	40.00 18.2%

13. Secondary Outcome

Title	Overall Survival (OS)
Description	Defined as the interval from study enrollment to death due to any cause.
Time Frame	End of Study up to approximately 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Median (Full Range) [days]	365	348.5

14. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events With INCB39110
Description	Adverse events reported for the first time or worsening of a pre-existing event after the first dose of study treatment
Time Frame	30-35 days after end of treatment, approximately 24 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	215	216
Number [participants]	208 95%	214 97.3%

15. Secondary Outcome

Title	Incidence Rate of Secondary Graft Failure
Description	Defined as > 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (< 0.5 × 109/L) and/or thrombocytopenia (< 20 × 109/L) within 2 months of transplantion
Time Frame	Randomization through end of Study, study duration expected to average 24 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Number [participants]	2 0.9%	0 0%

16. Secondary Outcome

Title	Proportion of Subjects Who Discontinue Corticosteroids
Description	Average and cumulative corticosteroid dose usage will be calculated and proportion of subjects discontinuing corticosteroids will be tabulated
Time Frame	Days 28, 56, 100, and 180

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	215	216
Day 28	3 1.4%	3 1.4%
Day 56	16 7.3%	11 5%
Day 100	39 17.8%	45 20.5%
Day 180	39 17.8%	45 20.5%

17. Secondary Outcome

Title	Proportion of Subjects Who Discontinue Immunosuppressive Medications
Description	Summary statistics of subjects discontinuing immunosuppressive medications will be calculated
Time Frame	Days 56 and 100

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Day 56	12 5.5%	10 4.5%
Day 100	11 5%	8 3.6%

18. Secondary Outcome

Title	Incidence Rate of aGVHD Flares
Time Frame	up to day 100

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Number [participants]	42 19.2%	48 21.8%

19. Secondary Outcome

Title	Incidence Rate of cGVHD
Time Frame	Days 180 and 365

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Day 180	25 11.4%	36 16.4%
Day 365	43 19.6%	58 26.4%

20. Secondary Outcome

Title	Objective Response Rate
Time Frame	Days 14, 56 and 100

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population

Arm/Group Title	Itacitinib Plus Corticosteroids	Placebo Plus Corticosteroids
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.	Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.
Measure Participants	219	220
Day 14	170 77.6%	160 72.7%
Day 56	138 63%	124 56.4%
Day 100	92 42%	96 43.6%

Adverse Events

Time Frame	30 days after last dose approximately up to 24 months
Arm/Group Title	Itacitinib Plus Corticosteroids		Placebo Plus Corticosteroids		Total
Arm/Group Description	Itacitinib was administered at a starting dose of 200 mg orally once daily QD (2 × 100 mg tablets) in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.		Matching placebo was administered orally once daily QD in combination with steroids i.e. methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose that is appropriate for the severity of the disease.		Total
All Cause Mortality
	Itacitinib Plus Corticosteroids		Placebo Plus Corticosteroids		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/215 (32.1%)		69/216 (31.9%)		138/431 (32%)
Serious Adverse Events
	Itacitinib Plus Corticosteroids		Placebo Plus Corticosteroids		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	133/215 (61.9%)		131/216 (60.6%)		264/431 (61.3%)
Blood and lymphatic system disorders
Anaemia	3/215 (1.4%)	3	2/216 (0.9%)	2	5/431 (1.2%)	5
Bicytopenia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Febrile neutropenia	7/215 (3.3%)	8	8/216 (3.7%)	10	15/431 (3.5%)	18
Hypofibrinogenaemia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Leukopenia	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Microangiopathic haemolytic anaemia	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Neutropenia	3/215 (1.4%)	3	3/216 (1.4%)	3	6/431 (1.4%)	6
Pancytopenia	4/215 (1.9%)	5	0/216 (0%)	0	4/431 (0.9%)	5
Thrombocytopenia	3/215 (1.4%)	3	6/216 (2.8%)	6	9/431 (2.1%)	9
Thrombotic microangiopathy	3/215 (1.4%)	3	3/216 (1.4%)	3	6/431 (1.4%)	6
Agranulocytosis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Bone marrow failure	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Haemolysis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Cardiac disorders
Atrial fibrillation	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Atrial flutter	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Cardiac arrest	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Cardiac failure congestive	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Myocardial infarction	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Congenital, familial and genetic disorders
Bartter's syndrome	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Ear and labyrinth disorders
Vertigo	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Eye disorders
Photophobia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Gastrointestinal disorders
Abdominal pain	2/215 (0.9%)	2	5/216 (2.3%)	5	7/431 (1.6%)	7
Diarrhoea	10/215 (4.7%)	11	13/216 (6%)	15	23/431 (5.3%)	26
Diverticular perforation	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Gastritis erosive	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Haemoperitoneum	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Ileus	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Large intestinal haemorrhage	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Lower gastrointestinal haemorrhage	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Nausea	2/215 (0.9%)	2	1/216 (0.5%)	1	3/431 (0.7%)	3
Pancreatitis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Pneumatosis intestinalis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Vomiting	3/215 (1.4%)	3	4/216 (1.9%)	4	7/431 (1.6%)	7
Anal haemorrhage	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Anal inflammation	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Gastrointestinal haemorrhage	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Intestinal ischaemia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Small intestinal obstruction	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Upper gastrointestinal haemorrhage	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
General disorders
Asthenia	2/215 (0.9%)	2	2/216 (0.9%)	2	4/431 (0.9%)	4
Fatigue	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
General physical health deterioration	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Multiple organ dysfunction syndrome	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Oedema	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Oedema peripheral	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Pyrexia	15/215 (7%)	19	10/216 (4.6%)	10	25/431 (5.8%)	29
Hepatobiliary disorders
Cholecystitis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Hepatic failure	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Venoocclusive liver disease	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Immune system disorders
Acute graft versus host disease	1/215 (0.5%)	1	3/216 (1.4%)	3	4/431 (0.9%)	4
Acute graft versus host disease in skin	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Graft versus host disease	1/215 (0.5%)	1	3/216 (1.4%)	3	4/431 (0.9%)	4
Graft versus host disease in gastrointestinal tract	3/215 (1.4%)	3	6/216 (2.8%)	6	9/431 (2.1%)	9
Graft versus host disease in lung	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Acute graft versus host disease in intestine	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Hypersensitivity	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Infections and infestations
Abscess	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Acute sinusitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Adenovirus infection	3/215 (1.4%)	3	1/216 (0.5%)	1	4/431 (0.9%)	4
Aspergillus infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
BK virus infection	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Bacteraemia	0/215 (0%)	0	4/216 (1.9%)	4	4/431 (0.9%)	4
Bacterial sepsis	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Bronchitis	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Bronchopulmonary aspergillosis	3/215 (1.4%)	3	1/216 (0.5%)	1	4/431 (0.9%)	4
Campylobacter infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Cerebral toxoplasmosis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Cholecystitis infective	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Clostridium difficile colitis	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Clostridium difficile infection	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Cystitis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Cytomegalovirus infection	2/215 (0.9%)	2	3/216 (1.4%)	3	5/431 (1.2%)	5
Cytomegalovirus infection reactivation	6/215 (2.8%)	6	1/216 (0.5%)	2	7/431 (1.6%)	8
Cytomegalovirus viraemia	5/215 (2.3%)	5	5/216 (2.3%)	5	10/431 (2.3%)	10
Diverticulitis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Encephalitis	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Enterovirus infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Epstein-Barr virus infection reactivation	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Escherichia infection	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Escherichia sepsis	2/215 (0.9%)	2	2/216 (0.9%)	2	4/431 (0.9%)	4
Fungal infection	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Gastroenteritis norovirus	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Gastroenteritis rotavirus	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Gastrointestinal infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Herpes zoster	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Influenza	1/215 (0.5%)	1	3/216 (1.4%)	3	4/431 (0.9%)	4
Lower respiratory tract infection fungal	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Mucormycosis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Neutropenic sepsis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Ophthalmic herpes zoster	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Oral candidiasis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Oral herpes	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Pneumonia	11/215 (5.1%)	12	13/216 (6%)	15	24/431 (5.6%)	27
Pneumonia bacterial	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pneumonia cytomegaloviral	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Pneumonia influenzal	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Pneumonia necrotising	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Pneumonia pneumococcal	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pneumonia pseudomonal	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pseudomonal sepsis	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Pseudomonas infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Respiratory syncytial virus infection	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Respiratory tract infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Respiratory tract infection fungal	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Rhinovirus infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Sepsis	5/215 (2.3%)	5	6/216 (2.8%)	6	11/431 (2.6%)	11
Septic shock	2/215 (0.9%)	2	6/216 (2.8%)	6	8/431 (1.9%)	8
Sinusitis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Staphylococcal bacteraemia	1/215 (0.5%)	1	4/216 (1.9%)	4	5/431 (1.2%)	5
Toxoplasmosis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Urinary tract infection	3/215 (1.4%)	4	1/216 (0.5%)	1	4/431 (0.9%)	5
Varicella zoster virus infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Viral diarrhoea	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Viral haemorrhagic cystitis	3/215 (1.4%)	3	0/216 (0%)	0	3/431 (0.7%)	3
Viral upper respiratory tract infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Wound infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Adenoviral hepatitis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Arthritis bacterial	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Cellulitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Coronavirus infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Cytomegalovirus colitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Disseminated aspergillosis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Enterococcal bacteraemia	0/215 (0%)	0	3/216 (1.4%)	3	3/431 (0.7%)	3
Epstein-Barr virus infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Escherichia bacteraemia	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Fungal sepsis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Gastrointestinal candidiasis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Klebsiella sepsis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Meningoencephalitis herpetic	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Osteomyelitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Parainfluenzae virus infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Peritonitis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Pseudomonal bacteraemia	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pyelonephritis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Sepsis syndrome	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Sinusitis aspergillus	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Sinusitis fungal	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Streptococcal urinary tract infection	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Upper respiratory tract infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Urosepsis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Vascular device infection	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Injury, poisoning and procedural complications
Extradural haematoma	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Fall	1/215 (0.5%)	1	3/216 (1.4%)	3	4/431 (0.9%)	4
Foot fracture	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Wrist fracture	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Head injury	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Skin laceration	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Toxicity to various agents	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Transplant dysfunction	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Transplant failure	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Investigations
Alanine aminotransferase increased	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Aspartate aminotransferase increased	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Blood alkaline phosphatase increased	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Blood fibrinogen decreased	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Liver function test increased	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Neutrophil count decreased	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Weight decreased	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
White blood cell count decreased	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Blood bilirubin increased	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Clostridium test positive	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Electrocardiogram T wave abnormal	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Enterococcus test positive	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Klebsiella test positive	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Rotavirus test positive	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Transaminases increased	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Metabolism and nutrition disorders
Cachexia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Dehydration	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Failure to thrive	2/215 (0.9%)	2	2/216 (0.9%)	2	4/431 (0.9%)	4
Hypercholesterolaemia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Hyperglycaemia	4/215 (1.9%)	4	5/216 (2.3%)	5	9/431 (2.1%)	9
Hyperkalaemia	2/215 (0.9%)	2	3/216 (1.4%)	3	5/431 (1.2%)	5
Hypertriglyceridaemia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Hypokalaemia	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Malnutrition	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Metabolic acidosis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Steroid diabetes	2/215 (0.9%)	2	0/216 (0%)	0	2/431 (0.5%)	2
Musculoskeletal and connective tissue disorders
Muscular weakness	2/215 (0.9%)	2	1/216 (0.5%)	1	3/431 (0.7%)	3
Musculoskeletal pain	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Myopathy	3/215 (1.4%)	3	2/216 (0.9%)	2	5/431 (1.2%)	5
Pain in extremity	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Soft tissue necrosis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Amyotrophy	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Back pain	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Chronic lymphocytic leukaemia recurrent	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Malignant neoplasm progression	2/215 (0.9%)	2	2/216 (0.9%)	2	4/431 (0.9%)	4
Myelodysplastic syndrome	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Myeloid leukaemia	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Nasal cavity cancer	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Post transplant lymphoproliferative disorder	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
T-cell lymphoma recurrent	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Acute myeloid leukaemia recurrent	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Blast cell crisis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Leukaemia recurrent	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Nervous system disorders
Encephalopathy	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Lethargy	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Limbic encephalitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Neurotoxicity	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Peripheral motor neuropathy	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Posterior reversible encephalopathy syndrome	1/215 (0.5%)	2	0/216 (0%)	0	1/431 (0.2%)	2
Presyncope	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Seizure	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Syncope	4/215 (1.9%)	4	1/216 (0.5%)	1	5/431 (1.2%)	5
Toxic encephalopathy	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Altered state of consciousness	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Cerebral haemorrhage	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Cerebrovascular accident	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Diabetic coma	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Generalised tonic-clonic seizure	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Polyneuropathy	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Spinal subdural haematoma	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Status epilepticus	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Psychiatric disorders
Confusional state	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Mental status changes	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Substance-induced psychotic disorder	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	8/215 (3.7%)	8	5/216 (2.3%)	5	13/431 (3%)	13
Cystitis haemorrhagic	4/215 (1.9%)	4	0/216 (0%)	0	4/431 (0.9%)	4
Dysuria	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Haematuria	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Renal impairment	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Bullous oedema of the bladder	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Ureterolithiasis	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Reproductive system and breast disorders
Testicular pain	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Acute respiratory distress syndrome	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Acute respiratory failure	0/215 (0%)	0	2/216 (0.9%)	2	2/431 (0.5%)	2
Dyspnoea exertional	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Epistaxis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Haemothorax	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Hypoxia	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Obliterative bronchiolitis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Organising pneumonia	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Pleuritic pain	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Pneumonitis	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Pulmonary embolism	2/215 (0.9%)	2	2/216 (0.9%)	2	4/431 (0.9%)	4
Respiratory failure	3/215 (1.4%)	3	5/216 (2.3%)	5	8/431 (1.9%)	8
Chronic obstructive pulmonary disease	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Haemoptysis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pneumothorax	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Pulmonary alveolar haemorrhage	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Respiratory distress	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Skin and subcutaneous tissue disorders
Angioedema	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Ecchymosis	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Rash maculo-papular	1/215 (0.5%)	2	0/216 (0%)	0	1/431 (0.2%)	2
Vascular disorders
Hypotension	1/215 (0.5%)	1	2/216 (0.9%)	2	3/431 (0.7%)	3
Microangiopathy	1/215 (0.5%)	1	1/216 (0.5%)	1	2/431 (0.5%)	2
Embolism	1/215 (0.5%)	1	0/216 (0%)	0	1/431 (0.2%)	1
Shock	0/215 (0%)	0	1/216 (0.5%)	1	1/431 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Itacitinib Plus Corticosteroids		Placebo Plus Corticosteroids		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	207/215 (96.3%)		206/216 (95.4%)		413/431 (95.8%)
Blood and lymphatic system disorders
Anaemia	63/215 (29.3%)	80	54/216 (25%)	66	117/431 (27.1%)	146
Neutropenia	36/215 (16.7%)	57	40/216 (18.5%)	59	76/431 (17.6%)	116
Thrombocytopenia	73/215 (34%)	87	69/216 (31.9%)	77	142/431 (32.9%)	164
Leukopenia	6/215 (2.8%)	8	11/216 (5.1%)	14	17/431 (3.9%)	22
Pancytopenia	11/215 (5.1%)	11	6/216 (2.8%)	6	17/431 (3.9%)	17
Eye disorders
Dry eye	18/215 (8.4%)	18	17/216 (7.9%)	19	35/431 (8.1%)	37
Vision blurred	7/215 (3.3%)	7	12/216 (5.6%)	13	19/431 (4.4%)	20
Gastrointestinal disorders
Abdominal pain	26/215 (12.1%)	32	26/216 (12%)	28	52/431 (12.1%)	60
Constipation	25/215 (11.6%)	27	21/216 (9.7%)	22	46/431 (10.7%)	49
Diarrhoea	42/215 (19.5%)	48	43/216 (19.9%)	60	85/431 (19.7%)	108
Dry mouth	14/215 (6.5%)	15	18/216 (8.3%)	24	32/431 (7.4%)	39
Nausea	38/215 (17.7%)	47	33/216 (15.3%)	45	71/431 (16.5%)	92
Vomiting	23/215 (10.7%)	26	25/216 (11.6%)	27	48/431 (11.1%)	53
Dyspepsia	10/215 (4.7%)	10	13/216 (6%)	13	23/431 (5.3%)	23
General disorders
Asthenia	12/215 (5.6%)	15	19/216 (8.8%)	19	31/431 (7.2%)	34
Fatigue	28/215 (13%)	32	37/216 (17.1%)	54	65/431 (15.1%)	86
Oedema	7/215 (3.3%)	7	16/216 (7.4%)	16	23/431 (5.3%)	23
Oedema peripheral	53/215 (24.7%)	55	53/216 (24.5%)	61	106/431 (24.6%)	116
Pyrexia	34/215 (15.8%)	44	31/216 (14.4%)	38	65/431 (15.1%)	82
Infections and infestations
Cytomegalovirus infection	16/215 (7.4%)	20	10/216 (4.6%)	12	26/431 (6%)	32
Cytomegalovirus infection reactivation	26/215 (12.1%)	35	24/216 (11.1%)	26	50/431 (11.6%)	61
Cytomegalovirus viraemia	34/215 (15.8%)	38	26/216 (12%)	30	60/431 (13.9%)	68
Upper respiratory tract infection	17/215 (7.9%)	25	17/216 (7.9%)	19	34/431 (7.9%)	44
Urinary tract infection	15/215 (7%)	15	17/216 (7.9%)	19	32/431 (7.4%)	34
Epstein-Barr virus infection reactivation	11/215 (5.1%)	11	6/216 (2.8%)	6	17/431 (3.9%)	17
Nasopharyngitis	7/215 (3.3%)	8	11/216 (5.1%)	12	18/431 (4.2%)	20
Oral candidiasis	11/215 (5.1%)	13	11/216 (5.1%)	11	22/431 (5.1%)	24
Pneumonia	5/215 (2.3%)	6	11/216 (5.1%)	11	16/431 (3.7%)	17
Injury, poisoning and procedural complications
Fall	20/215 (9.3%)	22	21/216 (9.7%)	23	41/431 (9.5%)	45
Investigations
Alanine aminotransferase increased	30/215 (14%)	39	21/216 (9.7%)	23	51/431 (11.8%)	62
Aspartate aminotransferase increased	23/215 (10.7%)	37	13/216 (6%)	18	36/431 (8.4%)	55
Blood alkaline phosphatase increased	12/215 (5.6%)	14	16/216 (7.4%)	19	28/431 (6.5%)	33
Blood cholesterol increased	16/215 (7.4%)	19	11/216 (5.1%)	13	27/431 (6.3%)	32
Blood creatinine increased	25/215 (11.6%)	27	19/216 (8.8%)	20	44/431 (10.2%)	47
Gamma-glutamyltransferase increased	11/215 (5.1%)	11	7/216 (3.2%)	8	18/431 (4.2%)	19
Platelet count decreased	38/215 (17.7%)	45	22/216 (10.2%)	25	60/431 (13.9%)	70
Neutrophil count decreased	15/215 (7%)	18	9/216 (4.2%)	11	24/431 (5.6%)	29
Weight decreased	11/215 (5.1%)	11	8/216 (3.7%)	10	19/431 (4.4%)	21
White blood cell count decreased	12/215 (5.6%)	18	10/216 (4.6%)	11	22/431 (5.1%)	29
Metabolism and nutrition disorders
Decreased appetite	24/215 (11.2%)	26	23/216 (10.6%)	26	47/431 (10.9%)	52
Hyperglycaemia	47/215 (21.9%)	56	50/216 (23.1%)	57	97/431 (22.5%)	113
Hyperkalaemia	9/215 (4.2%)	11	16/216 (7.4%)	23	25/431 (5.8%)	34
Hypertriglyceridaemia	31/215 (14.4%)	33	27/216 (12.5%)	34	58/431 (13.5%)	67
Hypoalbuminaemia	12/215 (5.6%)	13	23/216 (10.6%)	26	35/431 (8.1%)	39
Hypocalcaemia	16/215 (7.4%)	17	20/216 (9.3%)	21	36/431 (8.4%)	38
Hypokalaemia	40/215 (18.6%)	51	35/216 (16.2%)	43	75/431 (17.4%)	94
Hypomagnesaemia	27/215 (12.6%)	46	21/216 (9.7%)	28	48/431 (11.1%)	74
Hyponatraemia	16/215 (7.4%)	27	22/216 (10.2%)	27	38/431 (8.8%)	54
Hypophosphataemia	14/215 (6.5%)	18	11/216 (5.1%)	13	25/431 (5.8%)	31
Musculoskeletal and connective tissue disorders
Arthralgia	23/215 (10.7%)	24	18/216 (8.3%)	19	41/431 (9.5%)	43
Back pain	17/215 (7.9%)	20	21/216 (9.7%)	25	38/431 (8.8%)	45
Muscular weakness	23/215 (10.7%)	24	19/216 (8.8%)	20	42/431 (9.7%)	44
Pain in extremity	14/215 (6.5%)	15	13/216 (6%)	13	27/431 (6.3%)	28
Nervous system disorders
Dizziness	23/215 (10.7%)	24	17/216 (7.9%)	19	40/431 (9.3%)	43
Headache	20/215 (9.3%)	21	32/216 (14.8%)	39	52/431 (12.1%)	60
Tremor	27/215 (12.6%)	28	19/216 (8.8%)	21	46/431 (10.7%)	49
Dysgeusia	11/215 (5.1%)	12	2/216 (0.9%)	3	13/431 (3%)	15
Neuropathy peripheral	6/215 (2.8%)	6	11/216 (5.1%)	11	17/431 (3.9%)	17
Psychiatric disorders
Insomnia	22/215 (10.2%)	23	25/216 (11.6%)	26	47/431 (10.9%)	49
Anxiety	17/215 (7.9%)	17	13/216 (6%)	13	30/431 (7%)	30
Renal and urinary disorders
Acute kidney injury	11/215 (5.1%)	13	21/216 (9.7%)	23	32/431 (7.4%)	36
Dysuria	17/215 (7.9%)	18	8/216 (3.7%)	8	25/431 (5.8%)	26
Respiratory, thoracic and mediastinal disorders
Cough	32/215 (14.9%)	35	42/216 (19.4%)	54	74/431 (17.2%)	89
Dyspnoea	28/215 (13%)	31	15/216 (6.9%)	19	43/431 (10%)	50
Rhinorrhoea	6/215 (2.8%)	6	14/216 (6.5%)	15	20/431 (4.6%)	21
Epistaxis	9/215 (4.2%)	9	11/216 (5.1%)	11	20/431 (4.6%)	20
Skin and subcutaneous tissue disorders
Pruritus	13/215 (6%)	14	17/216 (7.9%)	24	30/431 (7%)	38
Dry skin	6/215 (2.8%)	6	12/216 (5.6%)	16	18/431 (4.2%)	22
Rash	11/215 (5.1%)	11	3/216 (1.4%)	3	14/431 (3.2%)	14
Vascular disorders
Hypertension	46/215 (21.4%)	52	31/216 (14.4%)	35	77/431 (17.9%)	87
Hypotension	16/215 (7.4%)	16	11/216 (5.1%)	11	27/431 (6.3%)	27

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Clinical Study Agreement