Diffuse Cutaneous Systemic SclerosisPhase 2NCT04986605
Extracorporeal Photopheresis in Early Diffuse Cutaneous Systemic Sclerosis
A Phase 2 study testing Extracorporeal Photopheresis (ECP) and UVADEX in people with Diffuse Cutaneous Systemic Sclerosis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Cutaneous Systemic Sclerosis
- What is being tested?
- Extracorporeal Photopheresis (ECP) and UVADEX
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 14 May 2025to Jul 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Rheumatology Clinic, St. Joseph's Health Care
London, Ontario, N6A4V2
Dr. Janet E Pope, MD PhD, 519-646-6332, janet.pope@sjhc.london.on.ca
About this study
Official title: The Effectiveness of ECP in Diffuse Cutaneous Systemic Sclerosis
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.
Read the 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.
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Being tested
- Extracorporeal Photopheresis (ECP), UVADEX
- Keywords
- systemic sclerosis, scleroderma, extracorporeal photopheresis, connective tissue diseases, skin diseases
- Medical subject headings
- Scleroderma, Diffuse, Scleroderma, Systemic, Connective Tissue Diseases, Skin Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extracorporeal Photopheresis (ECP)Device
Also called ECP, 8-mop
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).
UVADEXDrug
Also called 8-mop
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.
| Study group | Role | What they receive |
|---|---|---|
| Administration of Extracorporeal Photopheresis Treatment | Experimental | Duration of treatment: 48 weeks. Treatments occur on 2 consecutive days every 4 weeks.
Dose of UVADEX: Treatment Volume x 0.017 = mL of UVADEX for each treatment Treatment Volume (TV) is defined as: The total volume of Buffy Coat plus prime solution that will undergo photoactivation.
Route of administration: Extracorporeal Receives: Device: Extracorporeal Photopheresis (ECP); Drug: UVADEX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in skin thickness measured by modified Rodnan Skin Score
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Measured: 48 weeks
Secondary outcomes (11)
Change in the modified Rodnan Skin Score
modified Rodnan Skin Score (mRSS): is a standard outcome measure for skin disease in SSc and calculated by measuring skin thickness in 17 different body sites (each site scored 0-3, with a total possible additive score of 51). A higher skin score (or a higher "skin thickness") and progression of this score, is predictive of internal organ involvement and mortality. While a lower or improving (lessening) score is associated with favorable outcomes, including better survival.
Measured: 12, 24 and 36 weeks
Combined Response Index in diffuse cutaneous systemic sclerosis score
CRISS score: It is calculated according to changes from the start of a study, compared to an endpoint, by using the modified Rodnan Skin Score (mRSS), the Health Assessment Questionnaire - Disability Index (HAQ-DI), patient and physician global assessment of scleroderma-related health, and forced vital capacity. A CRISS score of ≥ 0.6 indicates likelihood that a patient improved on treatment.
Will be calculated with baseline data and to define disease progression at 6 months.
Measured: 24 weeks
Change in Forced Vital Capacity
Change in Pulmonary Function as measured by percentage of Improving or worsening FVC.
The FVC (Forced vital Capacity) is the total amount of air exhaled during the FEV (Forced expiratory volume) test.
Measured: 6 and 12 months
Change in the diffusing capacity for carbon monoxide
Change in Pulmonary Function as measured by percentage of Improving or worsening DLCO.
The DLCO (diffusing capacity of the lungs for carbon monoxide) measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries.
Measured: 6 and 12 months
Change in physician global assessment of disease activity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease activity and 10 being the worst possible disease activity.
Measured: 12, 24, 36 and 48 weeks
Change in physician global assessment of disease severity
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease severity and 10 being the worst possible disease severity.
Measured: 12, 24, 36 and 48 weeks
Change in physician global assessment of disease damage
Measured on a Visual Analogue Scale (VAS) from 0-10, with 0 being no disease damage and 10 being the worst possible disease damage.
Measured: 12, 24, 36 and 48 weeks
Change in patient global assessment of health status
Measured on a Visual Analogue Scale (VAS) from 0-100, with 0 being no overall effect of disease on participant, and 100 being the worst possible overall effect of disease on participant.
This is a patient reported outcome.
Measured: 12, 24, 36 and 48 weeks
Change in Scleroderma Health Assessment Questionnaire
The SHAQ combines the disability and pain scales of the HAQ (HAQ-DI), with five scleroderma-specific Visual Analogue Scales for: digital ulcers, Raynaud's phenomenon, gastrointestinal (GI) symptoms, lung symptoms, and overall disease severity.
The HAQ-DI yields a score of 0-3, that indicates the extent of the respondent's functional limitations.
Each VAS score is scaled from 0 to 3, with 0 being no symptoms and 3 being the worst possible symptom severity.
A composite VAS score is not created nor are the individual VAS scores incorporated into the HAQ DI score. Typically, each VAS score is reported individually. There is a proposed way to obtain a combined score obtained by pooling the 8 domains of the HAQ DI and the 5 VASs; however, this approach has not yet been widely accepted.
This is a patient reported outcome.
Measured: 12, 24, 36 and 48 weeks
Change in serum concentrations C-Reactive Protein
Change in serum concentrations of the acute phase reactant, CRP
CRP aids in the evaluation of stress, trauma, infection, inflammation, surgery \& associated diseases. Blood levels of C-Reactive Protein (CRP) are known to rise in acute disease to a level of up to 50 mg/L in the presence of slight to moderate inflammatory process. Values >50 mg/L indicate high and extensive inflammatory activity.
Measured: 12, 24, 36 and 48 weeks
Change in serum concentrations of Erythrocyte Sedimentation Rate
Change in serum concentrations of the acute phase reactant, ESR
Reference ranges:
Male: 0-10 mm/h Female: 0-20 mm/h
A faster-than-normal rate may indicate inflammation in the body. Inflammation is part of the immune response system. The higher the number, the higher the likelihood of inflammation.
Measured: 12, 24, 36 and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start14 May 2025
- Primary completionJul 2028 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Diffuse Cutaneous Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt
- Responsible party
- Principal investigator, Janet Pope, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Dr. Janet E Pope, MD PhD, Principal investigator, University of Western Ontario, Division of Rheumatology, St. Joseph's Health Care, London, Ontario, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04986605
- Sponsor's protocol ID
- ECR-CAN-011068
- Status last verified
- Sep 2026
- First submitted
- 1 Jun 2021
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 22223705Nihtyanova 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.
PubMed 24591477Young 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.
PubMed 25775190Kowal-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 Sclerosis. Arthritis Rheumatol. 2016 Feb;68(2):299-311. doi: 10.1002/art.39501.
PubMed 26808827Valentini G, Silman AJ, Veale D. Assessment of disease activity. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S39-41.
PubMed 12889221Medsger 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.
PubMed 12889222Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol. 2010 May;22(3):264-72. doi: 10.1097/BOR.0b013e328337c3d6.
PubMed 20190640Becker MO, Bruckner C, Scherer HU, Wassermann N, Humrich JY, Hanitsch LG, Schneider U, Kawald A, Hanke K, Burmester GR, Riemekasten G. The monoclonal anti-CD25 antibody basiliximab for the treatment of progressive systemic sclerosis: an open-label study. Ann Rheum Dis. 2011 Jul;70(7):1340-1. doi: 10.1136/ard.2010.137935. Epub 2010 Nov 10. No abstract available.
PubMed 21068100Rook AH, Freundlich B, Jegasothy BV, Perez MI, Barr WG, Jimenez SA, Rietschel RL, Wintroub B, Kahaleh MB, Varga J, et al. Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial. Arch Dermatol. 1992 Mar;128(3):337-46.
PubMed 1550365Knobler RM, French LE, Kim Y, Bisaccia E, Graninger W, Nahavandi H, Strobl FJ, Keystone E, Mehlmauer M, Rook AH, Braverman I; Systemic Sclerosis Study Group. A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. J Am Acad Dermatol. 2006 May;54(5):793-9. doi: 10.1016/j.jaad.2005.11.1091.
PubMed 16635659Enomoto DN, Mekkes JR, Bossuyt PM, Yong SL, Out TA, Hoekzema R, de Rie MA, Schellekens PT, ten Berge IJ, de Borgie CA, Bos JD. Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis). J Am Acad Dermatol. 1999 Dec;41(6):915-22. doi: 10.1016/s0190-9622(99)70246-x.
PubMed 10570373Oon S, Huq M, Godfrey T, Nikpour M. Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus. Semin Arthritis Rheum. 2018 Oct;48(2):221-239. doi: 10.1016/j.semarthrit.2018.01.001. Epub 2018 Jan 6.
PubMed 29426575Pope JE, Baron M, Bellamy N, Campbell J, Carette S, Chalmers I, Dales P, Hanly J, Kaminska EA, Lee P, et al. Variability of skin scores and clinical measurements in scleroderma. J Rheumatol. 1995 Jul;22(7):1271-6.
PubMed 7562757Clements P, Lachenbruch P, Siebold J, White B, Weiner S, Martin R, Weinstein A, Weisman M, Mayes M, Collier D, et al. Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol. 1995 Jul;22(7):1281-5.
PubMed 7562759