Clinical trial NCT04164849: Extracorporeal Photopheresis of Patients With Crohn's Disease Using 5-aminolevulinic Acid
Official title: Extracorporeal Photopheresis of Patients With Crohn's Disease Using 5-aminolevulinic Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Crohn Disease
Keywords: Crohns Disease
Photopheresis
5-aminolevulinic acid
Gliolan
UVA-PIT
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
First posted: 2019-11-15
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A combined phase 1/2 pilot study with emphasize on safety/tolerability but also clinical efficacy/effect
Primary purpose: TREATMENT

Brief summary: In the clinical trial the investigators will assess efficacy, safety and tolerability after single and multiple doses of 3 millimolar 5 aminolevulinic acid (Gliolan®) in combination with blue-light (405 nanometer) photopheresis in patients with active crohns disease. The study is a proof-of-concept pilot with up to 10 included patients where every patient will get active treatment. The use of 5-aminolevulinic acid in combination with blue-light photopheresis is a first-in-human trial. Primary endpoints include clinical response and adverse events (safety). Secondary endpoints include endoscopic improvement, quality of life questionnaires, faecal calprotectin, C-reactive protein and mechanisms of action (differences in t-cells and other cells before and after treatment). All patients will get treatment every 2 weeks for 10 weeks (6 treatments-induction) with evaluation at week 13. If any effect on week 13 eligible for study extension with treatment every 4 weeks for up to 12 months for the first 5 patients. The latter 5 patients will be referred to standard of care on the week 13 visit. Through the study the investigators will see if this kind of photopheresis is safe and can be an option for a larger randomized-controlled-trial. In addition the investigators will see if photopheresis as an option can be further developed for other diseases as well (ie other T-cell mediated diseases or patients already receiving photopheresis as a treatment).


Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Age above 18
3. Male or female patient with active Crohn's disease (6)
4. Women of childbearing potential (WOCBP) will have to use highly effective methods of contraception throughout the entire study.
5. Inadequate response (a) or intolerance to biological therapy

   a. Inadequate response on ongoing treatment is defined as: i. Progressive disease: increasing Harvey Bradshaw Index/Calprotectin/Simple Endoscopic Score for Crohns Disease and/or worsening of radiologic images after 6 months.

   ii. Stable disease: no-response after 6 months
6. Active inflammation in the gut documented by

   1. Harvey Bradshaw Index \>5 and
   2. Endoscopy with Simple Endoscopic Score for Crohns Disease equal to or above 6 points or equal to or above 4 points if only isolated ileitis is present and/or
   3. Inflammatory marker; fecal calprotectin \> 250 and/or C reactive protein \> 5

Exclusion Criteria:

1. Photosensitive comorbidities, porphyria or known hypersensitivity to 5-aminolevulinic acid or porphyrins
2. Patients with aphakia
3. Pregnant or breast-feeding women. A negative urine pregnancy test must be demonstrated in female patients of child-bearing potential at the Screening Visit and before every treatment.
4. Ongoing cardiac and pulmonary diseases or aspartate transaminase alanine aminotransferase, Bilirubin or International Normalized Ratio value ≥ 3x upper limit of normal or clinically significant electrocardiogram findings
5. Subjects with polyneuropathy
6. Uncontrolled infection or fever
7. History of heparin-induced thrombocytopenia, absolute neutrophil count \<1x109, platelet count \<20x10 9
8. Body weight below 40 kg
9. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements.
10. Presence of other gastrointestinal diseases potentially influencing the study endpoints
11. History of any clinically significant disease or disorder which in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the result or the patient's ability to participate in the study.

Primary outcomes:
measure: Clinical response
timeFrame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and 3 months after last treatment
measure: Safety and tolerability adverse events
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-PR interval
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-PR segment
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-QT interval
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-ST segment
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-T wave
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability Electrocardiogram-QRS complex
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability vital signs
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Safety and tolerability blood pressure
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Alkaline phosphatase
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Aspartate transferase
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Alanine aminotransferase
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Albumin
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Bilirubin
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Gamma glutamyltransferase
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: White cell count
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Neutrophil granulocytes
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Lymphocytes
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Monocytes
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Eosinophile granulocytes
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Basophile granulocytes
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Platelet count
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Mean Cell Volume
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Mean Cell hemoglobin
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: International Normalized Ratio
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Hemoglobin
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Calcium
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Potassium
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Sodium
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Creatinin
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Lactate Dehydrogenase
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Cholesterol
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Total Protein
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
measure: Carbamide
timeFrame: Before every treatment visit (every second week from week 0-10, every 4th week from week 14-62, week 28 for patients not eligible for study extension and latter 5 patients) in addition to week 64 and 3 months after last treatment.
Secondary outcomes:
measure: CD4+ and CD8+ T cell subpopulations
timeFrame: Week 0, 10 (all patients) and 50 (patients of the first 5 subjects eligible for study extension)
measure: Apoptosis and necrosis
timeFrame: Week 0, 10 (all patients) and 50 (patients of the first 5 subjects eligible for study extension)
measure: Clinical remission
timeFrame: Week 13 and/or sustained/delayed response in week 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and 3 months after last treatment.
measure: Endoscopic efficacy
timeFrame: Week 13 (all patients) and 64 (patients of the first 5 subjects eligible for study extension) with baseline visit as reference.
measure: Faecal calprotectin
timeFrame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and/or 3 months after last treatment
measure: Concentration of C reactive protein in blood
timeFrame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and/or 3 months after last treatment
measure: Quality of life questionnaire Short-Form 36 (SF-36)
timeFrame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and/or 3 months after last treatment
measure: Quality of life questionnaire Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: Week 13, 26 (28 for patients not eligible for study extension and the latter 5 patients), 38, 50, 64 and/or 3 months after last treatment
Other outcomes:
Locations:
city: Lorenskog
country: Norway
facility: Akershus University Hospital
state: Akershus
Study officials:
References: