Diffuse Cutaneous Systemic SclerosisPhase 2NCT05149768
Open Label Extension Study of Brentuximab Vedotin in Early dcSSc
A Phase 2 study testing Brentuximab vedotin 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 safety and efficacy of Brentuximab vedotin, a CD30-directed antibody-drug conjugate, in patients with active diffuse cutaneous systemic sclerosis (dcSSc) who relapsed after discontinuation of Brentuximab vedotin. 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?
- Brentuximab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteCanada
- Study dates
- 14 Feb 2024to 23 Jul 2025
- 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 diffuse cutaneous systemic sclerosis enrolled in the Phase II Adcetris study (BV201708) at St. Joseph's Health centre, aged 18 years or older, and:
- Worsening mRSS of ≥ 4 points as compared to mRSS score at the end of treatment visit (week 48) in the initial study (BV201708).
- Able to give informed consent.
Who cannot join
- Poor pulmonary function (FVC<40% and/or DLCO<30%).
- Pregnancy, breast feeding or child bearing potential without practicing highly effective contraception (and partners for men in the study).
- Clinically significant pulmonary hypertension requiring drug therapy.
- Clinically significant cardiac disease.
- Chronic or ongoing active infectious disease requiring systemic treatment.
- Seropositivity for human immunodeficiency virus (HIV).
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- Active tuberculosis (TB) infection.
- Active viral infection with viral replication of hepatitis B or C virus.
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, pancreatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease; and cancer.
- Peripheral neuropathy at screening Grade 2 or higher.
- Known or suspected hypersensitivity to components of the treatment
- Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
- Any of the following laboratory abnormalities at screening:
- Absolute neutrophils count <2.0 x 109/L
- Hemoglobin <85 g/L
- Platelet count < 100 x 109/L
- AST/SGOT or ALT/SGPT >2.0 UNL
- Participation in another clinical trial within six weeks before randomization in this study, with the exception of continuation from the initial study BV201708.
- Use of rituximab within the previous 4 months.
- Immunization with a live/ attenuated vaccine less than 4 weeks prior to the baseline visit.
- Current or history of progressive multifocal leukoencephalopathy (PML).
Trial locations and contacts
1 site in 1 country.
Canada1 site
Rheumatology Clinic, St. Joseph's Health Care
London, Ontario, N6A 4V2
About this study
Official title: An Open Label Extension Study of Brentuximab Vedotin Treatment in Active Diffuse Cutaneous Systemic Sclerosis (Diffuse Scleroderma)
The purpose of this study is to assess safety and efficacy of Brentuximab vedotin, a CD30-directed antibody-drug conjugate, in patients with active diffuse cutaneous systemic sclerosis (dcSSc) who relapsed after discontinuation of Brentuximab vedotin.
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. Internal organ involvement results in increased mortality of SSc patients. There is no effective treatment for the majority of patients with early active diffuse scleroderma (diffuse cutaneous systemic sclerosis; dcSSc). It's possible to reverse immune inflammation and reduce the probability of irreversible fibrosis early in the disease course via significant immune modulation. The preliminary results of the Phase II study of Brentuximab vedotin (Protocol BV201708) in SSc demonstrated the short-term safety and benefits of this treatment as many participants already achieved the primary endpoint at 24 weeks. This study is proposed as an extension of the ongoing protocol for up to 48 weeks to make the treatment available for SSc patients who have significantly improved on Brentuximab vedotin, but relapsed after discontinuation of the treatment. Similar to the ongoing Phase II study, the Health Assessment Questionnaire Disability Index (HAQ-DI), patient and physician global scores, inflammatory markers (ESR, CRP), and combined response index in SSc (CRISS) and changes in CD30-stained cells on skin biopsies with IHC will all be exploratory outcomes.
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Being tested
- Brentuximab vedotin
- Keywords
- systemic sclerosis, scleroderma, brentuximab vedotin, CD30-directed antibody-drug conjugate, antirheumatic agents, antineoplastic agents, skin diseases, immunologic factors
- Medical subject headings
- Scleroderma, Diffuse, Scleroderma, Systemic, Skin Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab vedotinDrug
Also called ADCETRIS, SGN-35
Dose 0.6mg/kg will be given every 3 weeks for 16 cycles (48 weeks), in addition to standard of care medications for SSc that may include cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil (MMF, cellcept) and mycophenolic acid (myfortic)
| Study group | Role | What they receive |
|---|---|---|
| Administration of Brentuximab vedotin | Experimental | Maximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous Receives: Drug: Brentuximab vedotin |
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
Skin improvement is defined as the mean mRSS decrease of ≥8 points
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 skin thickness over time 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: 12 weeks and 36 weeks
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 (SHAQ)
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 the diffusing capacity for carbon monoxide (pulmonary function)
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.
% Improving/worsening DLCO. Analyzed as an ordinal outcome.
*PFT (pulmonary function test) results will only be analyzed as available under standard of care.
Measured: 24 and 48 weeks*
Change in Forced Vital Capacity (pulmonary function)
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.
% Improving/worsening FVC. Analyzed as an ordinal outcome.
*PFT (pulmonary function test) results will only be analyzed as available under standard of care.
Measured: 24 and 48 weeks*
Combined Response Index in diffuse cutaneous systemic sclerosis score (CRISS)
To define disease progression
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.
Measured: Baseline (week 0), and at 24, 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 posted8 Dec 2021
- Study start14 Feb 2024
- Primary completion23 Jul 2025
- Study completion23 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (30)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
- 3 participants (actual)
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
- Seattle Genetics (now a wholly owned subsidiary of Pfizer), Pfizer
- Responsible party
- Principal investigator, Janet Pope, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Janet E Pope, 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
- NCT05149768
- Sponsor's protocol ID
- BV202108
- Status last verified
- Sep 2026
- First submitted
- 24 Nov 2021
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- 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 22223705Young 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 25775190Shah AA, Casciola-Rosen L, Rosen A. Review: cancer-induced autoimmunity in the rheumatic diseases. Arthritis Rheumatol. 2015 Feb;67(2):317-26. doi: 10.1002/art.38928. No abstract available.
PubMed 25371098Andras C, Ponyi A, Constantin T, Csiki Z, Szekanecz E, Szodoray P, Danko K. Dermatomyositis and polymyositis associated with malignancy: a 21-year retrospective study. J Rheumatol. 2008 Mar;35(3):438-44. Epub 2008 Jan 15.
PubMed 18203322Hasegawa M, Sato S, Sakai H, Ohashi T, Takehara K. Systemic sclerosis revealing T-cell lymphoma. Dermatology. 1999;198(1):75-8. doi: 10.1159/000018070.
PubMed 10026408Juarez M, Marshall R, Denton C, Evely R. Paraneoplastic scleroderma secondary to hairy cell leukaemia successfully treated with cladribine. Rheumatology (Oxford). 2008 Nov;47(11):1734-5. doi: 10.1093/rheumatology/ken367. Epub 2008 Sep 23. No abstract available.
PubMed 18812428Khanna 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 12889222Oflazoglu E, Simpson EL, Takiguchi R, Grewal IS, Hanifin JM, Gerber HP. CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with disease severity. Eur J Dermatol. 2008 Jan-Feb;18(1):41-9. doi: 10.1684/ejd.2008.0309. Epub 2007 Dec 18.
PubMed 18086588Clements 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 7562759Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, Silman AJ, Allegar N, Varga J, Massa M, et al. Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993 Nov;20(11):1892-6.
PubMed 8308774Furst DE, Khanna D, Mattucci-Cerinic M, Silman AJ, Merkel PA, Foeldvari I; OMERACT 7 Special Interest Group. Scleroderma--developing measures of response. J Rheumatol. 2005 Dec;32(12):2477-80.
PubMed 16331791Pope JE, Bellamy N. Outcome measurement in scleroderma clinical trials. Semin Arthritis Rheum. 1993 Aug;23(1):22-33. doi: 10.1016/s0049-0172(05)80024-1.
PubMed 8235663van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013 Nov;65(11):2737-47. doi: 10.1002/art.38098. Epub 2013 Oct 3.
PubMed 24122180