his study will explore the safety and activity of ECP treatment with UVADEX in inducing a
clinical response (i. e., a CDAI decrease greater than or equal to 100 from baseline and/or a
CDAI < 150) over a 12-week period in moderately active Crohn’s disease (CDAI greater than or
equal to 220 to < 450) patients who are refractory or intolerant to immunosuppressants and/or
anti-TNF agents. This study will also assess response to continued treatment during a
12-week Extension Period in patients who have a clinical response at Week 12 of the Treatment
Period and elect to participate in the Extension Period.
Inclusion Criteria:
- Signed and dated informed consent must be obtained prior to conducting any study
procedure.
- Patients must be greater than or equal to 18 years of age.
- Patients must have a body weight greater than or equal to 40 kg (88 lb).
- Patients must have had Crohnâs disease for at least 6 months duration (with colitis,
ileitis, or ileocolitis) confirmed by radiography or endoscopy.
- Patients must have a CDAI greater than or equal to 220 to < 450.
- Patients must have a CRP concentration > 10. 0 mg/L (1. 0 mg/dL) or evidence of active
inflammatory luminal Crohnâs disease as demonstrated by superficial and/or deep
ulcerations, pseudopolyps, and/or ulcerated stenosis on colonoscopy within 8 weeks of
screening.
- Patients who are receiving corticosteroids must be on a prednisone equivalent dose
less than or equal to 25 mg/day or an oral (PO) budesonide dose less than or equal to
9 mg/day.
- Patients who are receiving any of the following concomitant Crohnâs disease
medications must have been on a stable dose of these medications for the specified
period of time PRIOR TO confirmation of eligibility (this time period may include
screening): aminosalicylates, antibiotics, and immunosuppressants (i. e., 6 MP, MTX, or
AZA) for at least 4 weeks; corticosteroids or PO budesonide for at least 2 weeks;
anti-TNF agents (i. e., infliximab or adalimumab) for at least 8 weeks.
- Patients who have failed treatment with immunosuppressants and/or anti-TNF agents.
Patients are considered to have failed treatment with these medications if they are
refractory or intolerant to their use, regardless of prior or ongoing treatment with
corticosteroids.
Refractoriness to immunosuppressant therapies and/or anti-TNF agents is defined as patients
continuing to have active Crohnâs disease despite prior or current treatment with one or
more of the following: AZA 2-3 mg/kg/day for 12 weeks; 6-MP 1. 0-1. 5 mg/kg/day for 12 weeks;
MTX 25 mg/wk for 8 weeks; infliximab greater than or equal to 5 mg/kg for 4 weeks (at least
one infusion); adalimumab greater than or equal to 40 mg subcutaneous (SC) for 4 weeks (at
least two injections).
Intolerance to immunosuppressants and/or anti-TNF agents is defined as patients
experiencing related side effects to one or more of the agents listed above that limit or
proscribe their use (e. g. leukopenia, hepatitis, infusion reactions, or drug-induced lupus)
at doses needed to adequately control the activity of their Crohnâs disease.
- Patients who have discontinued treatment with any of the following Crohnâs disease
medications must have done so for the specified period of time prior to confirmation
of eligibility (this time period may include screening): antibiotics,
aminosalicylates, corticosteroids, or PO budesonide for at least 2 weeks;
immunosuppressants (i. e., 6-MP, MTX, or AZA), or anti TNF agents (i. e., infliximab or
adalimumab) for at least 8 weeks; other investigative therapies - non biologics for at
least 4 weeks and biologics for at least 8 weeks.
- Patients who have fistulae are permitted, provided: patients have predominantly
luminal Crohnâs disease, and fistulae are not associated with abscess formation.
- Patients must have a platelet count greater than or equal to 50,000/microL (50. 0 x
109/L).
- Female patients must be: postmenopausal, surgically incapable of bearing children, or
practicing an acceptable method of birth control (acceptable methods include hormonal
contraceptives, intrauterine device, and spermicide and barrier). Abstinence or
partner/spouse sterility may also qualify at the Investigatorâs discretion. If a
female patient is of childbearing potential, she must have a negative urine pregnancy
test at screening. Male patients must also commit to using adequate contraceptive
precautions (condoms). All patients (both males and females of childbearing
potential) must commit to using adequate contraceptive precautions throughout their
participation in the study and for at least 3 months following their last ECP
treatment
- Patients must be able and willing to comply with all study procedures.
Exclusion Criteria:
- Patients who are concomitantly using biologic agents other than anti-TNF agents;
cyclosporine (CSA), tacrolimus (FK506), mycophenolate mofetil (MMF), or
investigational Crohnâs disease therapies.
- Patients who, in the opinion of the Investigator, may not be able to remain on a
stable dose of a concomitant Crohnâs disease medication during the 12-week Treatment
Period.
- Patients with currently symptomatic untreated diarrhea, due to conditions other than
inflammatory Crohnâs disease (e. g., bacterial or parasitic gastroenteritis, bile salt
diarrhea, or bacterial overgrowth).
- Patients with symptomatic intestinal strictures.
- Patients with stomas.
- Patients with other local manifestations of Crohnâs disease such as abscesses, or
other disease manifestations for which surgery might be indicated, or which might
preclude utilization of a CDAI to assess response to therapy (such as âshort gutâ
syndrome).
- Patients who are unable to tolerate the extracorporeal volume shifts associated with
ECP treatment due to the presence of any of the following conditions: uncompensated
congestive heart failure, pulmonary edema, severe chronic obstructive pulmonary
disease, severe asthma, renal failure, or hepatic failure.
- Patients receiving total parenteral nutrition, as the sole source of nutrition, within
3 weeks of screening.
- Female patients whose hemoglobin (Hgb) is < 8. 5 g/dL or male patients whose Hgb is <
10. 0 g/dL at screening.
- Patients with a poor tolerability of venipuncture or a lack of adequate venous access
for required treatments and blood sampling.
- Patients who have a known hypersensitivity or allergy to psoralen (methoxsalen).
- Patients who have a known hypersensitivity or allergy to both heparin and citrate
products.
- Female patients who are pregnant and/or lactating.
- Patients who have been enrolled in any investigational study for the treatment of
Crohnâs disease within 4 weeks of enrollment for non biologic therapies and within 8
weeks of enrollment for biologic therapies.
- Patients who have any of the following: a co-existing melanoma, squamous cell skin
carcinoma, aphakia, photosensitive disease (e. g., porphyria, systemic lupus
erythematosus, or albinism), a white blood cell count > 25,000 mm3, a previous
splenectomy, or a clinically significant coagulation disorder.
General Hospital of Vienna, Vienna, Austria
Hospital Erasme/ULB, Brussels, Belgium
UZ Leuven, Leuven, Belgium
Universitat St Josef, Bochum, Germany
Krankenhaus Duren gem.GmbH, Duren, Germany
Universitatsklinik Essen, Essen, Germany
Universitatsklinikum, Jena, Germany
Universitatsklinikum Mannheim, Mannheim, Germany
University Hospital Munich-Grosshadem, Munich, Germany
Klinikum Oldenberg, Oldenburg, Germany
Medizinische Universitatsklinik Ulm, Ulm, Germany
NIH, Bethesda, Maryland, United States
Metropolitian Gastroenterology Group, Chevy Chase, Maryland, United States
Morristown Memorial Hospital, Morristown, New Jersey, United States
Mount Sinai Medical Center, New York, New York, United States
