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Diffuse Cutaneous Systemic SclerosisPhase 2NCT03198689

Brentuximab Vedotin in Early Diffuse Cutaneous Systemic Sclerosis

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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to assess feasibility, safety and preliminary efficacy of Brentuximab vedotin (Adcetris), a CD30-directed antibody-drug conjugate, in the treatment of active diffuse cutaneous systemic sclerosis (dcSSc). 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
11 participants
Where
1 siteCanada
Study dates
7 May 2019to 28 Aug 2023
Phase
Phase 2
Are there results?
None posted in the registry

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

  • age 18 years or older
  • able to give informed consent
  • meet the ACR/EULAR classification criteria for SSc
  • early dcSSc (disease duration ≤ 5 years from first non-Raynaud's phenomenon symptom) OR active dcSSc as determined by worsening mRSS, presence of tendon friction rubs, and/or elevated inflammatory markers thought to be due to active dcSSc and not related to other issues
  • mRSS≥ 15
  • a negative TB skin test at screening, or treatment with INH for 6 months or other standardized LBTI (latent TB infection) treatment in the past

Who cannot join

  • Poor pulmonary function (FVC<40% and/or DLCO<30%).
  • Pregnancy, breast feeding or child bearing potential without practicing reliable 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) at study entry.
Show all 22Show fewer
  • Active tuberculosis (TB) infection.
  • Active viral infection with viral replication of hepatitis B or C virus at study entry.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, pancreatic, haematological, 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 <2000/mm3
  • Hemoglobin <85 g/L
  • Platelet count < 100,000/mm3
  • AST/SGOT or ALT/SGPT >2.0 UNL
  • Participation in another clinical trial within six weeks before randomization in this study
  • Use of rituximab within the previous 4 months.
  • Immunization with a live/ attenuated vaccine less than 4 weeks prior to the baseline visit.
  • Previous use of brentuximab vedotin.
  • 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

Other trials in Canada

About this study

Official title: A Pilot Study of Adcetris Treatment in Active Diffuse Cutaneous Systemic Sclerosis (Diffuse Scleroderma)

The purpose of this study is to assess feasibility, safety and preliminary efficacy of Brentuximab vedotin (Adcetris), a CD30-directed antibody-drug conjugate, in the treatment of active diffuse cutaneous systemic sclerosis (dcSSc).

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). These patients early in their disease may be able to reverse their inflammation and reduce the probability of irreversible fibrosis via significant immune modulation. This is a pilot study that will treat 10 patients with early or active dcSSc who meet inclusion criteria to determine if the benefit of Brentuximab vedotin and safety are favorable in order to consider a randomized controlled trial. This is a Phase II study that is uncontrolled and patients will remain on their background immune suppressive treatment unless if contraindicated for safety or drug interactions. The trial is powered to show a mean change in mRSS of 8 over one year in an uncontrolled, unblinded study. The Health Assessment Questionnaire Disability Index (HAQ), patient and physician global scores, inflammatory markers (ESR, CRP), and combined response index in SSc (CRISS) will all be exploratory outcomes. Other outcomes such as changes in CD30-stained cells on skin biopsies with IHC from baseline to end of the trial will be explored if the study is positive.

Being tested
Brentuximab Vedotin
Keywords
systemic sclerosis, scleroderma, brentuximab vedotin, CD30-directed antibody-drug conjugate, antirheumatic agents, antineoplastic agents, connective tissue diseases, skin diseases, immunologic factors
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.

  • Brentuximab VedotinDrug

    Also called ADCETRIS, SGN-35

    Dose 0.6 mg/kg i.v. 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, mycophenylate mofetil (MMF, cellcept) and mycophenolic acid (myfortic).

Study groups in NCT03198689
Study groupRoleWhat they receive
Administration of Brentuximab vedotinExperimentalMaximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous use
Receives: Drug: Brentuximab Vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in skin thickness measured by modified Rodnan Skin Score (mRSS)

    Measured: 12 months

Secondary outcomes (8)

  1. Change in mRSS

    Measured: 3, 6 and 9 months

  2. CRISS score >20%

    Measured: 6 months

  3. Change in FVC, %

    Measured: 6 and 12 months

  4. Change in DLCO, %

    Measured: 6 and 12 months

  5. Change in physician-assessed disease activity, severity and damage on VASs ranked from 0 to 10

    Measured: 3,6,9 and 12 months

  6. Change in patient global assessment of health status (VAS 0 to 10)

    Measured: 3,6,9 and 12 months

  7. Change in Health Transition score

    Measured: 3,6,9 and 12 months

  8. Change in SHAQ

    Measured: 3,6,9 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2017
  2. Study start7 May 2019
  3. Primary completion7 Jun 2023
  4. Study completion28 Aug 2023

Resources

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
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03198689
Sponsor's protocol ID
BV201708
Status last verified
Oct 2023
First submitted
14 Jun 2017
Last updated
4 Oct 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 25775190

  • Shah 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 25371098

  • Pope 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 7562757

  • Furst 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 16331791

  • Pope 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 8235663

  • Sutherland MS, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, Lewis TS, Meyer DL, Zabinski RF, Doronina SO, Senter PD, Law CL, Wahl AF. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006 Apr 14;281(15):10540-7. doi: 10.1074/jbc.M510026200. Epub 2006 Feb 16.

    PubMed 16484228

  • Fernandez-Codina A, Nevskaya T, Baron M, Appleton CT, Cecchini MJ, Philip A, El-Shimy M, Vanderhoek L, Pinal-Fernandez I, Pope JE. Brentuximab vedotin for skin involvement in refractory diffuse cutaneous systemic sclerosis, an open-label trial. Rheumatology (Oxford). 2025 Mar 1;64(3):1476-1481. doi: 10.1093/rheumatology/keae235.

    PubMed 38652570

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in skin thickness measured by modified Rodnan Skin Score (mRSS) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03198689, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.

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