Extracorporeal Photopheresis of Patients With Crohn's Disease Using 5-aminolevulinic Acid

Study Purpose

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 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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04164849
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital, Akershus
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Norway
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Crohn Disease

Arms & Interventions

Arms

Experimental: 5-ALA photopheresis

All patients will receive 5-aminolevulinic acid (5-ALA) in combination with blue light photopheresis. The investigators will collect mononuclear cells by connecting patient to Spectra Optia with CMNC (continuous mononuclear cell collection protocol), and these cells will include active T-lymphocytes. 5-ALA will be incubated for 1 hour to produce photoactive protoporphyrin-IX (PpIX) before light exposure.

Interventions

Drug: - 5-aminolevulinic acid

5-aminolevulinic acid (30 mg/ml) will be added to mononuclear cells in a dose of 3 millimolar and incubated for 1 hour

Procedure: - Blue light photopheresis

The mononuclear cells incubated with 5-aminolevulinic acid for 1 hour will be exposed to blue light.

Procedure: - Transfusion

The treated cells are transferred back to the patient as a standard blood transfusion

Procedure: - Continuous Mononuclear Cell Collection (CMNC)

The mononuclear cells are collected using the Spectra Optia with the Continuous Mononuclear Cell Collection protocol. 90 ml of mononuclear cells will be collected and 100 ml of 0,9% saline will be added to dilute the cells before incubation with drug and photopheresis.

Contact a Trial Team

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International Sites

Akershus University Hospital, Lorenskog, Akershus, Norway

Status

Recruiting

Address

Akershus University Hospital

Lorenskog, Akershus, 1478

Site Contact

Jorgen Jahnsen, PhD

jorgen.jahnsen@medisin.uio.no

+4767966013

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