Methoxsalen and Extracorporeal Photopheresis (ECP) for the Treatment of Pediatric Participants With Steroid Refractory Acute Graft Versus Host Disease

• Sponsor: Therakos, Inc., a Mallinckrodt Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02524847
• Collaborator: (none)
• Enrollment: 29
• Locations: 32
• Arm: 1
• Actual Duration (Months): 41.8
• Patients Per Site: 0.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, multicenter study of the efficacy of UVADEX® (methoxsalen) Sterile Solution in conjunction with THERAKOS® CELLEX® Photopheresis Systems (ECP) in pediatric participants with steroid-refractory aGvHD. The study is composed of Screening, Treatment, and Follow-up Periods.

Condition or Disease	Intervention/Treatment	Phase
Steroid Refractory Acute Graft Versus Host Disease	Drug: Methoxsalen; Procedure: Extracorporeal Photopheresis (ECP)	Phase 3

Detailed Description

Screening:

After the informed consent/assent form (ICF) is signed, the screening assessments will be performed in a single visit to establish the eligibility of the participant, based on inclusion and exclusion criteria, as well as aGvHD grading. Scheduling of the first week of ECP treatments and the arrangements for availability of typed and cross-matched donor packed red blood cells (PRBCs) for transfusion, if required, will be made in advance of participants entering the Treatment Period.

Treatment Period:

Once eligibility is established, participants will enter the 12-week ECP Treatment Period. The availability of typed and cross-matched donor PRBCs for transfusion during treatment, if needed, should be established prior to the scheduling of ECP treatments.

Participants will be allowed to continue standard aGvHD prophylaxis regimens (e.g., cyclosporine, tacrolimus, methotrexate, mycophenolate mofetil) without the addition of new therapies. Participants will be allowed to discontinue prophylaxis regimens for reasons of toxicity, and will also be allowed to switch to another prophylaxis medication within the same class (e.g., the calcineurin inhibitors cyclosporine and tacrolimus) for reasons of toxicity.

All participants enrolled in this trial will have received corticosteroids for the treatment of aGvHD. After entering the treatment period on study, tapering of steroids by total weekly decrements of 12.5% to 25% of the steroid dose at initiation of ECP therapy is permitted after a sustained response of aGvHD has been observed for at least 3 consecutive days, with the suggested goal to decrease the starting steroid dose by at least 50% 4 weeks after initiation of ECP.

Follow-Up Period:

After completion of the 12-week Treatment Period, participants may continue ECP treatment on commercial product at the Principal Investigator's discretion. Acute GvHD status will be assessed 4 weeks after completion of the Treatment Period. Participant survival will be assessed by passive follow-up (chart review) 26 weeks after initiation of ECP treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Single-Arm Study to Assess the Efficacy of UVADEX® (Methoxsalen) Sterile Solution in Conjunction With the THERAKOS® CELLEX® Photopheresis System in Pediatric Patients With Steroid-Refractory Acute Graft-vs-Host Disease (aGvHD)
• Actual Study Start Date: Jan 20, 2016
• Actual Primary Completion Date: Jul 16, 2019
• Actual Study Completion Date: Jul 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Methoxsalen with ECP Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.	Drug: Methoxsalen; Sterile solution used in conjunction with photopheresis procedure.; Other Names: UVADEX® ; Procedure: Extracorporeal Photopheresis (ECP); Other Names: THERAKOS® CELLEX® Photopheresis System

Outcome Measures

Primary Outcome Measures

1. Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4 [4 weeks]

   OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment

Secondary Outcome Measures

1. Number of Participants With Adverse Events [16 weeks]

   Clinically significant changes in vital signs, laboratory values and investigations are reported as adverse events. Summary data are provided below, with details listed in the adverse events module.

2. Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8 [8 weeks]

   OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment

3. Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12 [12 weeks]

   OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment

4. Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index [16 weeks]

   Duration of first response is presented for patients whose disease progressed. Duration of response is defined in the following way: Patients whose response failed: Date at which 1st disease progression occurs - date of 1st response +1. Patients whose response did not relapse: Date of 16 week follow-up or final assessment prior to week 16 (if patient withdrew early) - date of 1st response.

5. Overall Response Rate (ORR) According to the Modified Glucksberg Criteria [4 weeks, 8 weeks, and 12 weeks]

   ORR is defined as the percentage of patients who achieve an overall response after 4 weeks, 8 weeks, and 12 weeks of ECP treatment according to a scoring algorithm applied to calculate the grade of aGvHD using the modified Glucksberg Criteria.

6. Cumulative Dose of Daily Steroids [From diagnosis of aGvHD to 12 Weeks]

   Steroids administered from diagnosis of aGvHD to 12 Weeks after initiation of ECP treatment

7. Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria [at 4, 8 and 12 weeks]

   Number of patients whose skin was rated as Stage 0 - 4 using the modified Glucksberg criteria based on the Graft versus Host Disease (GvHD) rash - Stages are defined as 0=No GvHD rash, 1=Maculopapular rash on <25% body surface area (BSA), 2=Maculopapular rash on 25-50% BSA, 3=Maculopapular rash on >50% BSA, and 4=Generalized erythroderma plus bullous formation, which are blisters bigger than 5 mm across

8. Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria [at 4, 8 and 12 weeks]

   Number of patients whose liver was rated as Stage 0 - 4 on the modified Glucksberg criteria - Stages are based on level of bilirubin, defined as: Stage 0 = Bilirubin < 2.0 mg/dL, Stage 1 = Bilirubin 2.0-3.0 mg/dL, Stage 2 = Bilirubin 3.1-6.0 mg/dL, Stage 3 = Bilirubin 6.1-15.0 mg/dL, and Stage 4 = Bilirubin > 15.0 mg/dL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

1. Male or female 1 to 21 years of age at the time of consent

2. Steroid-refractory grade B-D aGvHD.

• Steroid-refractory is defined as a failure to respond to steroid treatment, with failure to respond defined as any grade B-D (IBMTR grading) aGvHD that shows progression ≥ 3 days, or no improvement by 5 days of treatment with 2 mg/kg/day methylprednisolone or equivalent in participants with lower gastrointestinal (GI) or liver disease, or skin disease associated with bullae. Grade D organ involvement will be limited to skin and liver.

• Steroid refractory may also be defined as a failure to respond to 1 mg/kg/day of methylprednisolone or equivalent in participants with disease confined to upper GI disease or lesser degrees of skin GvHD

• Participants with lack of complete response after 2 weeks of steroid treatment

1. A Lansky scale Performance Status score ≥ 30

2. Laboratory values are within the following limits, assessed within 3 days of the first study treatment:

• Absolute neutrophil count > 0.5 × 10^9/liter (L)

• Creatinine level < 2 times the upper limit of normal

1. For participants with isolated upper GI symptoms, pre-Screening biopsy results to confirm diagnosis of aGvHD

2. Female participants of childbearing potential and nonsterilized males who are sexually active with a female partner must be practicing highly effective, reliable, and medically approved contraceptive regimen throughout their participation in the study and for 3 months following the last ECP treatment. Or, for the US only, abstinence may be used in place of an approved contraceptive regimen. Females of childbearing potential are those who have reached the onset of menarche, or 8 years of age, whichever comes first. Approved contraceptive methods for female participants of childbearing potential or nonsterilized males who are sexually active with a female partner are as follows:

• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

• Established use of oral, injectable, or implanted hormonal methods of contraception.

• Placement of an intrauterine device or intrauterine system

1. Signed informed consent/assent is obtained before conducting any study procedures; the parent, legal guardian, or legally authorized representative of a minor must also provide written informed consent

Exclusion:

1. Currently enrolled in another clinical trial for the treatment of aGvHD

2. Use of any experimental regimens or medication(s) for aGvHD treatment

3. Treatment with > 2.0 mg/kg/day of methylprednisolone equivalents for aGvHD within 30 days prior to the first study treatment

4. Overt signs of relapse of the underlying condition

5. Uncontrolled viral, fungal, or bacterial infection

6. Platelet count < 20.0 × 10^9/L, despite platelet transfusion

7. Inability to tolerate the extracorporeal volume shifts associated with ECP treatment

8. Uncontrolled GI bleeding

9. Veno-occlusive liver disease

10. Life expectancy < 4 weeks

11. Participant requires invasive ventilation or vasopressor support

12. Known human immunodeficiency virus (HIV) or hepatitis B or C virus infection (proof of seronegativity within 6 months of screening is required)

13. Known allergy or hypersensitivity to methoxsalen, Uvadex, or its excipients

14. Known hypersensitivity and allergy to heparin and Anticoagulant Citrate Dextrose Formula-A (ACD-A)

15. Co-existing photosensitive disease (e.g., porphyria, systemic lupus erythematosus, albinism) or aphakia

16. Coagulation disorders that cannot be corrected with simple transfusion

17. Co-existing melanoma, basal cell, or squamous cell skin carcinoma

18. Previous splenectomy

19. White blood cell count greater than 25,000 cubic millimeter (mm^3)

20. Currently being treated with any systemic immunosuppressive or biologic therapy for the treatment of a medical condition other than aGvHD

21. Female participant is breastfeeding or pregnant

22. Any medical concerns that may pose risk to the participant

23. Any psychological, familial, sociological, and/or geographical condition that may potentially hamper compliance with the study protocol and follow-up schedule

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
3	Yale University	New Haven	Connecticut	United States	06520
4	Children's National Medical Center	Washington	District of Columbia	United States	20010
5	Children's Healthcare of Atlanta, Emory - Children's Center	Atlanta	Georgia	United States	30322
6	Lurie Children's Hospital	Chicago	Illinois	United States	60611
7	Boston Children's Hospital	Boston	Massachusetts	United States	02115
8	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
9	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
10	University Hospitals Rainbow Babies & Children's	Cleveland	Ohio	United States	44106
11	Cleveland Clinic Children's	Cleveland	Ohio	United States	44195
12	Oregon Health and Science University	Portland	Oregon	United States	97239
13	Vanderbilt University Medical Center - Ingram Cancer Institute	Nashville	Tennessee	United States	37232
14	MD Anderson Cancer Care Center	Houston	Texas	United States	77030
15	University of Utah	Salt Lake City	Utah	United States	84112
16	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
17	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
18	St Anna Kinderspital	Wien		Austria	1090
19	Hopital Necker Enfants Malades	Paris		France	75015
20	Hôpital universitaire Robert Debré	Paris		France	75019
21	Universitätsklinikum Leipzig, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abteilung für Hämatologie und Internistische Onkologie	Leipzig		Germany	04103
22	Klinikum rechts der Isar, TU München, Klinik- und Poliklinik für Kinder- und Jugendmedizin, Kinderklinik München Schwabing	München		Germany	80804
23	University Hospital Tuebingen	Tübingen		Germany	72076
24	Universitaetsklinikum Ulm, Kinder- und Jugendmedizin	Ulm		Germany	89075
25	United St Istvan and St Laszlo Hospital	Budapest		Hungary	1097
26	U.O.C. Clinica di Oncoematologia Pediatrica Azienda Ospedaliera di Padova	Padova		Italy	35128
27	Pediatric Hospital Bambinu Gesu Rome	Rome		Italy	00165
28	Vall d'Hebron University Hospital	Barcelona		Spain	8035
29	Hospital Infantil Universitario "Nino Jesus"	Madrid		Spain	28009
30	University Hospital Salamanca	Salamanca		Spain	37007
31	Hospital LA FE	Valencia		Spain	46026
32	Great North Children's Hospital (RVI)	Newcastle		United Kingdom	NE1 4LP

Sponsors and Collaborators

• Therakos, Inc., a Mallinckrodt Company

Investigators

• Study Director: Clinical Team Leader, Mallinckrodt

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 27, 2017

More Information

Publications

None provided.

• Responsible Party: Therakos, Inc., a Mallinckrodt Company
• ClinicalTrials.gov Identifier: NCT02524847
• Other Study ID Numbers: TKS-2014-001
• First Posted: Aug 17, 2015
• Last Update Posted: Sep 11, 2020
• Last Verified: Jul 1, 2020

• 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
• Additional relevant MeSH terms: Graft vs Host Disease; Methoxsalen

Study Results

Participant Flow

Pre-assignment Detail	Participants were recruited by multiple treatment centers in the United States and Europe

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with extracorporeal photopheresis (ECP) procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Period Title: Overall Study
STARTED	29
Completed Treatment Up to Week 12	14
Started Second Line Treatment	5
COMPLETED	15
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.6 (5.02)
Sex: Female, Male (Count of Participants)
Female	12 41.4%
Male	17 58.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 17.2%
Not Hispanic or Latino	24 82.8%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	1 3.4%
Black or African American	2 6.9%
White	22 75.9%
Other	4 13.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Achieving Overall Response (OR) Using the Modified International Bone Marrow Transplant Registry (IBMTR) Severity Index at Week 4
Description	OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Count of Participants [Participants]	16 55.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Methoxsalen With ECP
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	t-test, 2 sided
	Comments	2-sided p-value for testing the null hypothesis H0: Standard therapy has a CR+PR rate = 10% after 4 weeks, using the exact Binomial test.
Method of Estimation	Estimation Parameter	Overall response rate (%)
	Estimated Value	55.2
	Confidence Interval	(2-Sided) 95%; 35.7 to 73.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Clinically significant changes in vital signs, laboratory values and investigations are reported as adverse events. Summary data are provided below, with details listed in the adverse events module.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Any serious AE	12 41.4%
Non-serious TEAE at 5% threshold	17 58.6%
Death for any cause	3 10.3%

3. Secondary Outcome

Title	Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 8
Description	OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Evaluable Participants (Participants with appropriate efficacy data at the given time point)

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	73.7 254.1%

4. Secondary Outcome

Title	Percentage of Participants Achieving Overall Response (OR) Using Modified IBMTR Severity Index at Week 12
Description	OR using the modified IBMTR Severity Index is defined as complete response (CR) + partial response (PR) as follows: CR: complete resolution of all signs and symptoms of aGvHD in all evaluable organs without addition of next-line systemic treatment PR: improvement of 1 stage in 1 or more aGvHD target organs without progression in others and without addition of next-line systemic treatment
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Evaluable Participants (Participants with appropriate efficacy data at the given time point)

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	14
Number (95% Confidence Interval) [percentage of participants]	78.6 271%

5. Secondary Outcome

Title	Duration of Response (Days) Within 16 Weeks Using Modified IBMTR Severity Index
Description	Duration of first response is presented for patients whose disease progressed. Duration of response is defined in the following way: Patients whose response failed: Date at which 1st disease progression occurs - date of 1st response +1. Patients whose response did not relapse: Date of 16 week follow-up or final assessment prior to week 16 (if patient withdrew early) - date of 1st response.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

Population meeting the criterion

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	18
Median (Full Range) [days]	13.5

6. Secondary Outcome

Title	Overall Response Rate (ORR) According to the Modified Glucksberg Criteria
Description	ORR is defined as the percentage of patients who achieve an overall response after 4 weeks, 8 weeks, and 12 weeks of ECP treatment according to a scoring algorithm applied to calculate the grade of aGvHD using the modified Glucksberg Criteria.
Time Frame	4 weeks, 8 weeks, and 12 weeks

Outcome Measure Data

Analysis Population Description

All participants with a score at the given time point

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Week 4	50 172.4%
Week 8	63.2 217.9%
Week 12	78.6 271%

7. Secondary Outcome

Title	Cumulative Dose of Daily Steroids
Description	Steroids administered from diagnosis of aGvHD to 12 Weeks after initiation of ECP treatment
Time Frame	From diagnosis of aGvHD to 12 Weeks

Outcome Measure Data

Analysis Population Description

All participants

Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Median (Full Range) [mg]	1917

8. Secondary Outcome

Title	Number of Patients With Skin Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Description	Number of patients whose skin was rated as Stage 0 - 4 using the modified Glucksberg criteria based on the Graft versus Host Disease (GvHD) rash - Stages are defined as 0=No GvHD rash, 1=Maculopapular rash on <25% body surface area (BSA), 2=Maculopapular rash on 25-50% BSA, 3=Maculopapular rash on >50% BSA, and 4=Generalized erythroderma plus bullous formation, which are blisters bigger than 5 mm across
Time Frame	at 4, 8 and 12 weeks

Outcome Measure Data

Analysis Population Description

All participants with scores at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Stage 0	9 31%
Stage 1	8 27.6%
Stage 2	3 10.3%
Stage 3	3 10.3%
Stage 4	0 0%
Stage 0	11 37.9%
Stage 1	5 17.2%
Stage 2	1 3.4%
Stage 3	1 3.4%
Stage 4	0 0%
Stage 0	10 34.5%
Stage 1	2 6.9%
Stage 2	1 3.4%
Stage 3	1 3.4%
Stage 4	0 0%

9. Secondary Outcome

Title	Number of Patients With Liver Rated as Stage 0 - 4 Using the Modified Glucksberg Criteria
Description	Number of patients whose liver was rated as Stage 0 - 4 on the modified Glucksberg criteria - Stages are based on level of bilirubin, defined as: Stage 0 = Bilirubin < 2.0 mg/dL, Stage 1 = Bilirubin 2.0-3.0 mg/dL, Stage 2 = Bilirubin 3.1-6.0 mg/dL, Stage 3 = Bilirubin 6.1-15.0 mg/dL, and Stage 4 = Bilirubin > 15.0 mg/dL
Time Frame	at 4, 8 and 12 weeks

Outcome Measure Data

Analysis Population Description

All participants with scores at the given time point

Arm/Group Title	All Participants
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
Measure Participants	29
Stage 0	19 65.5%
Stage 1	1 3.4%
Stage 2	1 3.4%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	13 44.8%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	12 41.4%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%

Adverse Events

Time Frame	Up to 16 weeks
Arm/Group Title	Methoxsalen With ECP
Arm/Group Description	Participants receive methoxsalen 20 µg/ml in conjunction with ECP procedure three times per week for Weeks 1 to 4, and two times per week for Weeks 5 to 12.
All Cause Mortality
	Methoxsalen With ECP
	Affected / at Risk (%)	# Events
Total	3/29 (10.3%)
Serious Adverse Events
	Methoxsalen With ECP
	Affected / at Risk (%)	# Events
Total	12/29 (41.4%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/29 (3.4%)
Pancytopenia	1/29 (3.4%)
General disorders
Pyrexia	2/29 (6.9%)
General physical health deterioration	1/29 (3.4%)
Immune system disorders
Acute graft versus host disease	2/29 (6.9%)
Acute graft versus host disease in intestine	1/29 (3.4%)
Acute graft versus host disease in liver	1/29 (3.4%)
Graft versus host disease	1/29 (3.4%)
Infections and infestations
Aspergilloma	1/29 (3.4%)
Bk virus infection	1/29 (3.4%)
Cellulitis	1/29 (3.4%)
Cystitis viral	1/29 (3.4%)
Cytomegalovirus infection	1/29 (3.4%)
Device related infection	1/29 (3.4%)
Hepatitis E	1/29 (3.4%)
Metabolism and nutrition disorders
Hyperkalaemia	1/29 (3.4%)
Hypokalaemia	1/29 (3.4%)
Hypomagnesaemia	1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/29 (3.4%)
Nervous system disorders
Haemorrhage intracranial	1/29 (3.4%)
Renal and urinary disorders
Cystitis haemorrhagic	1/29 (3.4%)
Renal failure	1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/29 (3.4%)
Vascular disorders
Hypertension	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Methoxsalen With ECP
	Affected / at Risk (%)	# Events
Total	17/29 (58.6%)
Gastrointestinal disorders
Abdominal pain	4/29 (13.8%)
Nausea	4/29 (13.8%)
General disorders
Pyrexia	3/29 (10.3%)
Immune system disorders
Hypogammaglobulinaemia	3/29 (10.3%)
Infections and infestations
Clostridium difficile infection	2/29 (6.9%)
Cytomegalovirus infection	2/29 (6.9%)
Pneumonia	2/29 (6.9%)
Investigations
Immunoglobulins decreased	2/29 (6.9%)
Metabolism and nutrition disorders
Hyperglycaemia	3/29 (10.3%)
Hypocalcaemia	3/29 (10.3%)
Hyperkalaemia	2/29 (6.9%)
Hypophosphataemia	2/29 (6.9%)
Malnutrition	2/29 (6.9%)
Psychiatric disorders
Depression	2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/29 (13.8%)
Vascular disorders
Hypertension	4/29 (13.8%)
Hypotension	3/29 (10.3%)

Limitations/Caveats

This study did have a notable limitation in its single-group study design. This may limit a more robust assessment vs standard of care alone for primary endpoint of overall response and secondary endpoints steroid sparing and disease progression.

More Information

Certain Agreements

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

There IS 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.