Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis

Официальное название

The Effectiveness of ECP in Diffuse Cutaneous Systemic Sclerosis

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Extracorporeal Photopheresis (ECP)
  Drug Intervention using a medical device. The ECP device is already licensed in Canada. License No.7703. ECP treatment, using the drug UVADEX, will be given on 2 consecutive days every 4 weeks for a total of 26 treatment days (48 weeks).
• Препарат UVADEX
  The phase II aspect of the study refers to the drug, methoxsalen. Methoxsalen is being used off label from the currently approved indications in the monograph. The study is proposing to use methoxsalen in combination with with extracorporeal photopheresis for the treatment of diffuse cutaneous systemic sclerosis. Treatment will be given in addition to standard of care medications for SSc.

Первичные конечные точки

• Change in skin thickness measured by modified Rodnan Skin Score [Срок оценки: 48 weeks]

Вторичные конечные точки (11)

• Change in the modified Rodnan Skin Score [Срок оценки: 12, 24 and 36 weeks]
• Combined Response Index in diffuse cutaneous systemic sclerosis score [Срок оценки: 24 weeks]
• Change in Forced Vital Capacity [Срок оценки: 6 and 12 months]
• Change in the diffusing capacity for carbon monoxide [Срок оценки: 6 and 12 months]
• Change in physician global assessment of disease activity [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in physician global assessment of disease severity [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in physician global assessment of disease damage [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in patient global assessment of health status [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in Scleroderma Health Assessment Questionnaire [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in serum concentrations C-Reactive Protein [Срок оценки: 12, 24, 36 and 48 weeks]
• Change in serum concentrations of Erythrocyte Sedimentation Rate [Срок оценки: 12, 24, 36 and 48 weeks]

Критерии участия

Критерии включения

• Patients with SSc, aged 18 years or older, and:
• Subjects must meet the ACR/EULAR classification criteria for SSc (2013).
• 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.
• Able to give informed consent.

Критерии исключения

• Poor pulmonary function (FVC<40% and/or DLCO<30%).
• Class IV PAH or PH.
• Clinically significant cardiac disease.
• 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).
• Chronic or ongoing active infectious disease requiring systemic treatment, including active tuberculosis (TB) infection.
• Seropositivity for human immunodeficiency virus (HIV) at study entry.
• Active viral infection with viral replication of hepatitis B or C virus at study entry.
• Thrombophilia.
• 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.
• Low Platelet count (less than 100,000 per mm3).
• 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.
• Severe anemia (hemoglobin <70g/L).
• High white blood cell count (greater than 25000 mm3).
• A history of surgical spleen removal.
• A history of a light sensitive disease state, i.e. lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum and albinism.
• Previous idiosyncratic reactions to psoralen compounds.
• 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.
• Treatment with more than 2 immunosuppressants (including mofetil mycophenolate, methotrexate, cyclophosphamide, biologics) at study entry.
• Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
• Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
• Participation in another clinical trial within six weeks before randomization in this study.
• Previous use of Extracorporeal photopheresis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Rheumatology Clinic, St. Joseph's Health Care — London

Публикации

• Komocsi A, Vorobcsuk A, Faludi R, Pinter T, Lenkey Z, Kolto G, Czirjak L. The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies. Rheumatology (Oxford). 2012 Jun;51(6):1027-36. doi: 10.1093/rheumatology/ker357. Epub 2012 Jan 5. PMID 22223705
• Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, Wells AU, Denton CP. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014 Jun;66(6):1625-35. doi: 10.1002/art.38390. PMID 24591477
• Young A, Khanna D. Systemic sclerosis: a systematic review on therapeutic management from 2011 to 2014. Curr Opin Rheumatol. 2015 May;27(3):241-8. doi: 10.1097/BOR.0000000000000172. PMID 25775190
• Kowal-Bielecka O, Veale DJ. DMARDs in systemic sclerosis: do they exist? In: Distler O, ed. Scleroderma-modern aspects of pathogenesis, diagnosis and therapy. Uni-MedVerlag AG: Bremen-London-Boston; 2009: 89-95.
• Khanna D, Berrocal VJ, Giannini EH, Seibold JR, Merkel PA, Mayes MD, Baron M, Clements PJ, Steen V, Assassi S, Schiopu E, Phillips K, Simms RW, Allanore Y, Denton CP, Distler O, Johnson SR, Matucci-Cerinic M, Pope JE, Proudman SM, Siegel J, Wong WK, Wells AU, Furst DE. The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic PMID 26808827
• Valentini G, Silman AJ, Veale D. Assessment of disease activity. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S39-41. PMID 12889221
• Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W. Assessment of disease severity and prognosis. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S42-6. PMID 12889222
• Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol. 2010 May;22(3):264-72. doi: 10.1097/BOR.0b013e328337c3d6. PMID 20190640

Идентификаторы

NCT: NCT04986605 · ECR-CAN-011068

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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