Clinical trial NCT04986605: Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis
Official title: The Effectiveness of ECP in Diffuse Cutaneous Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Diffuse Cutaneous Systemic Sclerosis
Keywords: systemic sclerosis
scleroderma
extracorporeal photopheresis
connective tissue diseases
skin diseases
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2021-08-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess feasibility, safety and preliminary efficacy of Extracorporeal Photopheresis in the treatment of active diffuse cutaneous systemic sclerosis (dcSSc). This pilot study will help to determine if further study (a RCT) is justified.

Detailed description: Systemic sclerosis (SSc, Scleroderma) is a multisystem autoimmune disease characterized by widespread vascular injury and progressive fibrosis of the skin and internal organs. There is no effective treatment for the majority of patients with diffuse scleroderma (diffuse cutaneous systemic sclerosis; dcSSc). Only few therapies have shown modest benefits in regard to some specific organ pathologies. In the early stage of dcSSc, it may be possible to reverse inflammation and reduce the probability of irreversible fibrosis via significant immune modulation as later, often the fibrosis doesn't improve with treatment.

This is a pilot study that will treat 15 participants with dcSSc who meet the eligibility criteria. The objective of the study is to determine if the benefit of Extracorporeal photopheresis (ECP) and safety are favorable in order to consider and help in the design of a randomized controlled trial (RCT). This is a Phase II study that is uncontrolled and patients will remain on their background immunosuppressive treatment unless if contraindicated for safety or drug interactions. The trial is powered to show a mean change in skin thickness measured with modified Rodnan skin score (mRSS) of ≥5 over one year, in an uncontrolled, unblinded study. The Health Assessment Questionnaire Disability Index (HAQ-DI), patient and physician global scores, inflammatory markers, and combined response index in SSc (CRISS) will all be exploratory outcomes. Other outcomes such as changes in cells on skin biopsies from baseline to end of the trial will be explored if the study is positive.

Eligibility criteria: Inclusion Criteria:

1. Patients with SSc, aged 18 years or older, and:
2. Subjects must meet the ACR/EULAR classification criteria for SSc (2013).
3. Early dcSSc (within 5 years of first non-Raynaud's phenomenon symptom) or any other dcSSc patients who have at least one of the signs of disease activity: mRSS of 15 or more, presence of tendon friction rubs, elevated inflammatory markers thought to be due to active dcSSc and not related to other issues such as infection or ILD with FVC% predicted \<80% or HRCT showing ILD thought to be from SSc.
4. Able to give informed consent.

Exclusion Criteria:

1. Poor pulmonary function (FVC\<40% and/or DLCO\<30%).
2. Class IV PAH or PH.
3. Clinically significant cardiac disease.
4. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, cardiac, hepatic, pancreatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease; and cancer (i.e. co-existing melanoma, basal cell, or squamous cell skin carcinoma).
5. Chronic or ongoing active infectious disease requiring systemic treatment, including active tuberculosis (TB) infection.
6. Seropositivity for human immunodeficiency virus (HIV) at study entry.
7. Active viral infection with viral replication of hepatitis B or C virus at study entry.
8. Thrombophilia.
9. Contraindications to heparin including history of heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis (HITTS), history of thrombocytopenia with pentosan polysulfate, known hypersensitivity to heparin or pork products.
10. Low Platelet count (less than 100,000 per mm3).
11. Aphakia (absence or loss of the eye's lens and has not been replaced with an artificial lens), because of the significantly increased risk of retinal damage due to the absence of lenses.
12. Severe anemia (hemoglobin \<70g/L).
13. High white blood cell count (greater than 25000 mm3).
14. A history of surgical spleen removal.
15. A history of a light sensitive disease state, i.e. lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.
16. Previous idiosyncratic reactions to psoralen compounds.
17. Patients who are using photosensitizing drugs such as anthralin, coal tar or coal tar derivatives, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides (bacteriostatic soaps), sulfonamides, tetracyclines, thiazides, and certain organic staining dyes such as methylene blue, toluidine blue, rose bengal and methyl orange.
18. Treatment with more than 2 immunosuppressants (including mofetil mycophenolate, methotrexate, cyclophosphamide, biologics) at study entry.
19. Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
20. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
21. Participation in another clinical trial within six weeks before randomization in this study.
22. Previous use of Extracorporeal photopheresis.

Primary outcomes:
measure: Change in skin thickness measured by modified Rodnan Skin Score
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in the modified Rodnan Skin Score
timeFrame: 12, 24 and 36 weeks
measure: Combined Response Index in diffuse cutaneous systemic sclerosis score
timeFrame: 24 weeks
measure: Change in Forced Vital Capacity
timeFrame: 6 and 12 months
measure: Change in the diffusing capacity for carbon monoxide
timeFrame: 6 and 12 months
measure: Change in physician global assessment of disease activity
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in physician global assessment of disease severity
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in physician global assessment of disease damage
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in patient global assessment of health status
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in Scleroderma Health Assessment Questionnaire
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in serum concentrations C-Reactive Protein
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in serum concentrations of Erythrocyte Sedimentation Rate
timeFrame: 12, 24, 36 and 48 weeks
Other outcomes:
measure: Regimen-related toxicities
timeFrame: assessed for duration of treatment up to 48 weeks, and up to 12 weeks post-treatment
measure: Infectious complications
timeFrame: assessed for duration of treatment up to 48 weeks, and up to 1 month post-treatment
measure: Change in peripheral levels of T-cell activation marker - sIL-2R
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in peripheral levels of fibrillogenesis - amino terminal propeptide of type III collagen
timeFrame: 12, 24, 36 and 48 weeks
measure: Change in CD3-positive cell count (T-cell marker) in skin biopsies of involved forearm skin
timeFrame: 24 and 48 weeks
measure: Change in myofibroblast count in skin biopsies of involved forearm skin
timeFrame: 24 and 48 weeks
Locations:
city: London
country: Canada
facility: Rheumatology Clinic, St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: University of Western Ontario, Division of Rheumatology, St. Joseph's Health Care, London, Ontario, Canada
name: Dr. Janet E Pope, MD PhD
role: PRINCIPAL_INVESTIGATOR
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