SUPPORTS: Study of orBec® With Prednisone Therapy in the Treatment of Patients With Graft Versus Host Disease (GVHD)

• Sponsor: Soligenix (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00926575
• Collaborator: (none)
• Enrollment: 140
• Locations: 3
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 46.7
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

Use of an oral topically-active glucocorticoid with limited side effects will control the gastrointestinal inflammatory process of GVHD and minimize glucocorticoid exposure.

Condition or Disease	Intervention/Treatment	Phase
Acute Gastrointestinal Graft vs Host Disease	Drug: oral beclomethasone 17,21-dipropionate; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of the Safety and Efficacy of orBec® (Oral Beclomethasone 17,21-Dipropionate)in Conjunction With Ten Days of High-Dose Prednisone Therapy in the Treatment of Patients With Gastrointestinal GVHD
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: orBec® Investigational drug	Drug: oral beclomethasone 17,21-dipropionate; Two tablets QID for 50 days; Other Names: orBec BDP
Placebo Comparator: Placebo Control	Drug: Placebo; Two tablets QID for 50 days

Outcome Measures

Primary Outcome Measures

1. The Proportion of Subjects With GVHD Treatment Failure [Day 80]

   The primary endpoint is the occurrence (yes, no) during the 80-day study period of GVHD treatment failure defined as use of prednisone or equivalent IV corticosteroids at doses higher than stated in the protocol, or use of any additional other glucocorticoid (including unblinded BDP) or addition of other immunosuppressant medications, in response to uncontrolled signs or symptoms of GVHD

Secondary Outcome Measures

1. Cumulative Exposure to Prednisone [Day 80]

2. Survival Status [Day 200]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Receipt of allogeneic hematopoietic cell transplant

• Diagnosis of GI graft vs. host disease (GVHD)

• No GI infection

• Must be able to swallow tablets

• Must be able to read and understand informed consent

• Adequate birth control methods for the duration of the study

Exclusion Criteria:

• Significant Skin GVHD

• Liver GVHD

• Persistent vomiting

• HIV positive

• Pregnancy/lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Buffalo	New York	United States
2		Durham	North Carolina	United States
3		Seattle	Washington	United States

Sponsors and Collaborators

• Soligenix

Investigators

• Principal Investigator: Keith Sullivan, MD, Duke University
• Principal Investigator: David Hockenbery, MD, Fred Hutchinson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hockenbery DM, Cruickshank S, Rodell TC, Gooley T, Schuening F, Rowley S, David D, Brunvand M, Berryman B, Abhyankar S, Bouvier M, McDonald GB. A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease. Blood. 2007 May 15;109(10):4557-63. Epub 2007 Jan 23.
• McDonald GB, Bouvier M, Hockenbery DM, Stern JM, Gooley T, Farrand A, Murakami C, Levine DS. Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host disease: a randomized, controlled trial. Gastroenterology. 1998 Jul;115(1):28-35.

• Responsible Party: Soligenix
• ClinicalTrials.gov Identifier: NCT00926575
• Other Study ID Numbers: BDP-GVHD-03
• First Posted: Jun 23, 2009
• Last Update Posted: Dec 6, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Soligenix: BDP; orBec; GVHD; beclomethasone dipropionate; bone marrow transplant; hematopoietic cell transplant; HCT; stem cell transplant; marrow transplant; SCT; beclomethasone 17,21-dipropionate
• Additional relevant MeSH terms: Graft vs Host Disease; Beclomethasone

Study Results

Participant Flow

Arm/Group Title	Active	Placebo
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)
Period Title: Overall Study
STARTED	70	70
COMPLETED	54	53
NOT COMPLETED	16	17

Baseline Characteristics

Arm/Group Title	Active	Placebo	Total
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)	Total of all reporting groups
Overall Participants	70	70	140
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	62 88.6%	66 94.3%	128 91.4%
>=65 years	8 11.4%	4 5.7%	12 8.6%
Sex: Female, Male (Count of Participants)
Female	34 48.6%	36 51.4%	70 50%
Male	36 51.4%	34 48.6%	70 50%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects With GVHD Treatment Failure
Description	The primary endpoint is the occurrence (yes, no) during the 80-day study period of GVHD treatment failure defined as use of prednisone or equivalent IV corticosteroids at doses higher than stated in the protocol, or use of any additional other glucocorticoid (including unblinded BDP) or addition of other immunosuppressant medications, in response to uncontrolled signs or symptoms of GVHD
Time Frame	Day 80

Outcome Measure Data

Analysis Population Description

Data was not analyzed as the study was terminated due to futility

Arm/Group Title	Active	Placebo
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)
Measure Participants	0	0

2. Secondary Outcome

Title	Cumulative Exposure to Prednisone
Time Frame	Day 80

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)
Measure Participants	0	0

3. Secondary Outcome

Title	Survival Status
Time Frame	Day 200

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)
Measure Participants	0	0

Adverse Events

Time Frame	Day 1 to Day 80
Arm/Group Title	Active		Placebo
Arm/Group Description	oral beclomethasone 17,21-dipropionate (BDP)
All Cause Mortality
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/70 (45.7%)		28/70 (40%)
Blood and lymphatic system disorders
Acute myeloid leukemia progression	0/70 (0%)		1/70 (1.4%)
Angiopathic Anemia	0/70 (0%)		1/70 (1.4%)
Leukemic Relapse	0/70 (0%)		1/70 (1.4%)
Multiple myeloma progression	1/70 (1.4%)		0/70 (0%)
Recurrent AML	1/70 (1.4%)		0/70 (0%)
Relapsed ALL	0/70 (0%)		1/70 (1.4%)
Relapsed AML	0/70 (0%)		1/70 (1.4%)
Thrombotic Thrombocytopenic purpura	0/70 (0%)		1/70 (1.4%)
Cardiac disorders
Atrial fibrillation	0/70 (0%)		1/70 (1.4%)
Endocrine disorders
Diabetic Ketoacidosis	1/70 (1.4%)		0/70 (0%)
Gastrointestinal disorders
Abdominal Cramps	1/70 (1.4%)		0/70 (0%)
Ascites	1/70 (1.4%)		0/70 (0%)
Diarrhea	4/70 (5.7%)		2/70 (2.9%)
Increased Abdominal Cramping	0/70 (0%)		1/70 (1.4%)
Intermittent Diarrhea	0/70 (0%)		1/70 (1.4%)
Intractable Nausea	0/70 (0%)		1/70 (1.4%)
Intractable vomiting	0/70 (0%)		1/70 (1.4%)
Loose Stool	0/70 (0%)		1/70 (1.4%)
Nausea	2/70 (2.9%)		1/70 (1.4%)
Obstruction gastric	0/70 (0%)		1/70 (1.4%)
Peritoneal Perforation	1/70 (1.4%)		0/70 (0%)
Vomiting	2/70 (2.9%)		1/70 (1.4%)
Watery Diarrhea	1/70 (1.4%)		0/70 (0%)
General disorders
Disease Progression	1/70 (1.4%)		1/70 (1.4%)
Drug Withdrawal Syndrome	0/70 (0%)		1/70 (1.4%)
DVT	1/70 (1.4%)		0/70 (0%)
Fatigue	0/70 (0%)		1/70 (1.4%)
Fever	2/70 (2.9%)		1/70 (1.4%)
Flank Pain	0/70 (0%)		1/70 (1.4%)
Multi-organ failure	1/70 (1.4%)		0/70 (0%)
Progressive disease	0/70 (0%)		1/70 (1.4%)
Immune system disorders
Acute GVHD flare	1/70 (1.4%)		0/70 (0%)
Lower GI GVHD	0/70 (0%)		1/70 (1.4%)
Infections and infestations
Back Pain	0/70 (0%)		1/70 (1.4%)
Bacteraemia	1/70 (1.4%)		1/70 (1.4%)
BK Viruria	1/70 (1.4%)		0/70 (0%)
BK Virus Cystitis	0/70 (0%)		1/70 (1.4%)
BK Virus Infection	1/70 (1.4%)		0/70 (0%)
Bronchiolitis	0/70 (0%)		1/70 (1.4%)
Clostridium difficile infection	1/70 (1.4%)		0/70 (0%)
CMV infection	2/70 (2.9%)		0/70 (0%)
CMV infection/reactivation	1/70 (1.4%)		0/70 (0%)
CMV Pneumonitis	1/70 (1.4%)		0/70 (0%)
CMV reaction	1/70 (1.4%)		0/70 (0%)
CMV Reactivation	0/70 (0%)		1/70 (1.4%)
Gram Negative Bacilli Hyperbilirubinemia	1/70 (1.4%)		0/70 (0%)
Gram Negative Bacteremia	1/70 (1.4%)		0/70 (0%)
Gram Positive Bacteremia	1/70 (1.4%)		0/70 (0%)
Lower Extremities Cellulitis	0/70 (0%)		1/70 (1.4%)
Nocardia sepsis	0/70 (0%)		1/70 (1.4%)
Pneumonia	1/70 (1.4%)		1/70 (1.4%)
Pneumonia fungal	1/70 (1.4%)		0/70 (0%)
Progressive multifocal leukoencephalopathy	1/70 (1.4%)		0/70 (0%)
Right orbital cellulitis	1/70 (1.4%)		0/70 (0%)
Rotavirus infection	1/70 (1.4%)		0/70 (0%)
Sepsis	1/70 (1.4%)		0/70 (0%)
Septic Pneumonia	0/70 (0%)		1/70 (1.4%)
Septic Shock	1/70 (1.4%)		0/70 (0%)
Skin GVHD	1/70 (1.4%)		0/70 (0%)
Staph Bacteremia	1/70 (1.4%)		0/70 (0%)
Viral Respiratory-type Infection	1/70 (1.4%)		0/70 (0%)
Injury, poisoning and procedural complications
Fall	0/70 (0%)		1/70 (1.4%)
Investigations
RSV Positive	0/70 (0%)		1/70 (1.4%)
Metabolism and nutrition disorders
Dehydration	0/70 (0%)		1/70 (1.4%)
Malnutrition	0/70 (0%)		1/70 (1.4%)
Poor PO Intake	0/70 (0%)		1/70 (1.4%)
Hyperglycaemia	2/70 (2.9%)		0/70 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	0/70 (0%)		1/70 (1.4%)
Weakness	0/70 (0%)		1/70 (1.4%)
Pain: Bone Diffuse	1/70 (1.4%)		0/70 (0%)
Nervous system disorders
Dizziness	0/70 (0%)		1/70 (1.4%)
Headache	0/70 (0%)		1/70 (1.4%)
Meningismus	0/70 (0%)		1/70 (1.4%)
Seizure	0/70 (0%)		1/70 (1.4%)
Psychiatric disorders
Mental Status Changes	1/70 (1.4%)		0/70 (0%)
Renal and urinary disorders
Acute Renal Failure	1/70 (1.4%)		0/70 (0%)
Renal failure	2/70 (2.9%)		1/70 (1.4%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress with Respiratory Failure	0/70 (0%)		1/70 (1.4%)
Hypoxia	0/70 (0%)		1/70 (1.4%)
Pleural effusion	1/70 (1.4%)		0/70 (0%)
Respiratory distress	1/70 (1.4%)		0/70 (0%)
Tachyarrhythmia absoluta	0/70 (0%)		1/70 (1.4%)
Vascular disorders
Hypertension Worsened	0/70 (0%)		1/70 (1.4%)
Other (Not Including Serious) Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/70 (100%)		70/70 (100%)
Blood and lymphatic system disorders
Anaemia	5/70 (7.1%)		4/70 (5.7%)
Neutropenia	7/70 (10%)		7/70 (10%)
Trombocytopenia	9/70 (12.9%)		6/70 (8.6%)
Cardiac disorders
Tachycardia	4/70 (5.7%)		6/70 (8.6%)
Endocrine disorders
Adrenal insufficiency	4/70 (5.7%)		3/70 (4.3%)
Eye disorders
Dry Eye	7/70 (10%)		1/70 (1.4%)
Vision Blurred	5/70 (7.1%)		4/70 (5.7%)
Gastrointestinal disorders
Abdominal distension	1/70 (1.4%)		4/70 (5.7%)
Abdominal pain	20/70 (28.6%)		14/70 (20%)
Abdominal pain upper	2/70 (2.9%)		3/70 (4.3%)
Constipation	5/70 (7.1%)		4/70 (5.7%)
Diarrhoea	33/70 (47.1%)		17/70 (24.3%)
Dry Mouth	9/70 (12.9%)		8/70 (11.4%)
Dyspepsia	5/70 (7.1%)		3/70 (4.3%)
Flatulence	5/70 (7.1%)		3/70 (4.3%)
Nausea	22/70 (31.4%)		21/70 (30%)
Retching	3/70 (4.3%)		0/70 (0%)
Vomiting	12/70 (17.1%)		17/70 (24.3%)
Pyrexia	12/70 (17.1%)		9/70 (12.9%)
General disorders
Asthenia	7/70 (10%)		6/70 (8.6%)
Early Satiety	4/70 (5.7%)		1/70 (1.4%)
Chills	2/70 (2.9%)		3/70 (4.3%)
Fatigue	17/70 (24.3%)		22/70 (31.4%)
Oedema	3/70 (4.3%)		2/70 (2.9%)
Oedema Peripheral	6/70 (8.6%)		8/70 (11.4%)
Immune system disorders
Acute graft versus host disease in skin	5/70 (7.1%)		5/70 (7.1%)
Hypogammagluobulinaemia	6/70 (8.6%)		3/70 (4.3%)
Infections and infestations
Bacteraemia	6/70 (8.6%)		1/70 (1.4%)
BK virus infection	5/70 (7.1%)		2/70 (2.9%)
Clostridial infection	4/70 (5.7%)		0/70 (0%)
Cytomegalovirus infection	15/70 (21.4%)		11/70 (15.7%)
Cytomegalovirus viraemia	5/70 (7.1%)		4/70 (5.7%)
Epstein- Barr virus infection	4/70 (5.7%)		1/70 (1.4%)
Staphylococcal infection	1/70 (1.4%)		3/70 (4.3%)
Upper respiratory tract infection	2/70 (2.9%)		3/70 (4.3%)
Investigations
Blood Creatinine increased	5/70 (7.1%)		5/70 (7.1%)
Breath sounds abnormal	3/70 (4.3%)		1/70 (1.4%)
Hepatic enzyme increased	3/70 (4.3%)		0/70 (0%)
Blood lactate dehyrogenase increase	1/70 (1.4%)		3/70 (4.3%)
Neutrophil count increased	0/70 (0%)		3/70 (4.3%)
Protein total decreased	1/70 (1.4%)		3/70 (4.3%)
Transaminases increased	2/70 (2.9%)		4/70 (5.7%)
Weight decreased	8/70 (11.4%)		5/70 (7.1%)
Metabolism and nutrition disorders
Anorexia	7/70 (10%)		3/70 (4.3%)
Cushingoid	5/70 (7.1%)		3/70 (4.3%)
Decreased appetite	16/70 (22.9%)		13/70 (18.6%)
Dehydration	3/70 (4.3%)		3/70 (4.3%)
Fluid retension	3/70 (4.3%)		0/70 (0%)
Fluid overload	0/70 (0%)		5/70 (7.1%)
Hyperglycaemia	11/70 (15.7%)		12/70 (17.1%)
Hyperkalaemia	9/70 (12.9%)		9/70 (12.9%)
Hypoalbuminaemia	2/70 (2.9%)		3/70 (4.3%)
Hypocalcaemia	1/70 (1.4%)		3/70 (4.3%)
Hypokalaemia	8/70 (11.4%)		9/70 (12.9%)
Hypomagnesaemia	6/70 (8.6%)		4/70 (5.7%)
Hyponatraemia	5/70 (7.1%)		4/70 (5.7%)
Hypophosphataemia	3/70 (4.3%)		4/70 (5.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/70 (5.7%)		4/70 (5.7%)
back pain	3/70 (4.3%)		5/70 (7.1%)
Muscular weakness	3/70 (4.3%)		6/70 (8.6%)
Myalgia	4/70 (5.7%)		5/70 (7.1%)
Pain in extremity	4/70 (5.7%)		3/70 (4.3%)
Nervous system disorders
Dizziness	3/70 (4.3%)		3/70 (4.3%)
Dysgeusia	3/70 (4.3%)		0/70 (0%)
Headache	9/70 (12.9%)		9/70 (12.9%)
Neuropathy peripheral	2/70 (2.9%)		4/70 (5.7%)
Tremor	7/70 (10%)		8/70 (11.4%)
Psychiatric disorders
Anxiety	4/70 (5.7%)		3/70 (4.3%)
Depression	7/70 (10%)		3/70 (4.3%)
Insomnia	9/70 (12.9%)		9/70 (12.9%)
Renal and urinary disorders
Dysuria	3/70 (4.3%)		5/70 (7.1%)
Haematuria	3/70 (4.3%)		0/70 (0%)
Pollakiuria	3/70 (4.3%)		1/70 (1.4%)
Renal failure	8/70 (11.4%)		6/70 (8.6%)
Respiratory, thoracic and mediastinal disorders
Cough	4/70 (5.7%)		12/70 (17.1%)
Dyspnoea	3/70 (4.3%)		5/70 (7.1%)
Dyspnoea exertional	5/70 (7.1%)		5/70 (7.1%)
Rales	0/70 (0%)		3/70 (4.3%)
Epstaxis	3/70 (4.3%)		2/70 (2.9%)
Nasal congestion	4/70 (5.7%)		2/70 (2.9%)
Wheezing	3/70 (4.3%)		2/70 (2.9%)
Rhinorrhoea	1/70 (1.4%)		7/70 (10%)
Sinus congestion	1/70 (1.4%)		3/70 (4.3%)
Skin and subcutaneous tissue disorders
Dry Skin	6/70 (8.6%)		0/70 (0%)
Ecchymosis	4/70 (5.7%)		0/70 (0%)
Erythema	4/70 (5.7%)		8/70 (11.4%)
Pruritus	5/70 (7.1%)		5/70 (7.1%)
Rash	9/70 (12.9%)		10/70 (14.3%)
Rash Macular	2/70 (2.9%)		3/70 (4.3%)
Vascular disorders
Deep vein thrombosis	3/70 (4.3%)		1/70 (1.4%)
Hypertension	19/70 (27.1%)		7/70 (10%)
Hypotension	3/70 (4.3%)		4/70 (5.7%)

Limitations/Caveats

DSMB terminated study for futility; no safety concerns during analysis of patient population. Overall, 1 SAE considered possibly related to study drug, all others were not related to study drug.

More Information

Certain Agreements

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