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

University Hospital, Akershus

Status and phase: Completed; Phase 2; Phase 1

Conditions: Crohn Disease

Treatments: Drug: 5-aminolevulinic acid; Procedure: Blue light photopheresis; Procedure: Continuous Mononuclear Cell Collection (CMNC); Procedure: Transfusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04164849

twostepala

Details and patient eligibility

About

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).

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

7 participants in 1 patient group

5-ALA photopheresis

Experimental group

Description:

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.

Treatment:

Procedure: Blue light photopheresis

Drug: 5-aminolevulinic acid

Procedure: Transfusion

Procedure: Continuous Mononuclear Cell Collection (CMNC)