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

NCT ID: NCT04164849

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-22
• Study Completion Date: 2023-10-31

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).

Conditions

Crohn Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

5-aminolevulinic acid

Intervention Type: DRUG

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

Blue light photopheresis

Intervention Type: PROCEDURE

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

Transfusion

Intervention Type: PROCEDURE

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

Continuous Mononuclear Cell Collection (CMNC)

Intervention Type: PROCEDURE

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.

Interventions

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

Intervention Type: DRUG

Blue light photopheresis

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

Intervention Type: PROCEDURE

Transfusion

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

Intervention Type: 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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: lead

Responsible Party

Jørgen Jahnsen

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Akershus University Hospital

Lorenskog, Akershus, Norway

Countries

Norway

Other Identifiers

twostepala

Identifier Type: -

Identifier Source: org_study_id