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Brentuximab Vedotin in Early Diffuse Cutaneous Systemic Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03198689
Recruitment Status : Recruiting
First Posted : June 26, 2017
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Janet Pope, Lawson Health Research Institute

Brief 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).

Condition or disease Intervention/treatment Phase
Diffuse Cutaneous Systemic Sclerosis Drug: Brentuximab Vedotin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Adcetris Treatment in Active Diffuse Cutaneous Systemic Sclerosis (Diffuse Scleroderma)
Actual Study Start Date : May 7, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : July 1, 2021


Arm Intervention/treatment
Experimental: Administration of Brentuximab vedotin
Maximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous use
Drug: Brentuximab Vedotin
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).
Other Name: ADCETRIS, SGN-35




Primary Outcome Measures :
  1. Change in skin thickness measured by modified Rodnan Skin Score (mRSS) [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Change in mRSS [ Time Frame: 3, 6 and 9 months ]
  2. CRISS score >20% [ Time Frame: 6 months ]
  3. Change in FVC, % [ Time Frame: 6 and 12 months ]
  4. Change in DLCO, % [ Time Frame: 6 and 12 months ]
  5. Change in physician-assessed disease activity, severity and damage on VASs ranked from 0 to 10 [ Time Frame: 3,6,9 and 12 months ]
  6. Change in patient global assessment of health status (VAS 0 to 10) [ Time Frame: 3,6,9 and 12 months ]
  7. Change in Health Transition score [ Time Frame: 3,6,9 and 12 months ]
  8. Change in SHAQ [ Time Frame: 3,6,9 and 12 months ]

Other Outcome Measures:
  1. Change in blood levels of soluble CD30 [ Time Frame: 3,6,9 and 12 months ]
  2. Change in serum levels of sIL-2R [ Time Frame: 3,6,9 and 12 months ]
  3. Change in serum levels of aminoterminal propeptide of type III collagen [ Time Frame: 3,6,9 and 12 months ]
  4. Change in myofibroblast score in skin biopsies of involved forearm skin [ Time Frame: 6 and 12 months ]
  5. Change in CD30-positive cell count in skin biopsies of involved forearm skin [ Time Frame: 6 and 12 months ]
  6. Change in erythrocyte sedimentation rate [ Time Frame: 3,6,9 and 12 months ]
  7. Change in hsCRP levels [ Time Frame: 3,6,9 and 12 months ]
  8. Number of patients with infectious complications [ Time Frame: up to 1 month post-treatment ]
  9. Number of patients with regimen-related toxicities [ Time Frame: up to 12 weeks post-treatment ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  1. Poor pulmonary function (FVC<40% and/or DLCO<30%).
  2. Pregnancy, breast feeding or child bearing potential without practicing reliable contraception (and partners for men in the study).
  3. Clinically significant pulmonary hypertension requiring drug therapy.
  4. Clinically significant cardiac disease.
  5. Chronic or ongoing active infectious disease requiring systemic treatment.
  6. Seropositivity for human immunodeficiency virus (HIV) at study entry.
  7. Active tuberculosis (TB) infection.
  8. Active viral infection with viral replication of hepatitis B or C virus at study entry.
  9. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, pancreatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease; and cancer.
  10. Peripheral neuropathy at screening Grade 2 or higher.
  11. Known or suspected hypersensitivity to components of the treatment
  12. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
  13. 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
  14. Participation in another clinical trial within six weeks before randomization in this study
  15. Use of rituximab within the previous 4 months.
  16. Immunization with a live/ attenuated vaccine less than 4 weeks prior to the baseline visit.
  17. Previous use of brentuximab vedotin.
  18. Current or history of progressive multifocal leukoencephalopathy (PML).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03198689


Contacts
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Contact: Janet E Pope, MD PhD 519-646-6332 janet.pope@sjhc.london.on.ca
Contact: Louise Vanderhoek 519-646-6000 ext 61022 Louise.Vanderhoek@sjhc.london.on.ca

Locations
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Canada, Ontario
Rheumatology Clinic, St. Joseph's Health Care Recruiting
London, Ontario, Canada, N6A 4V2
Contact: Janet E Pope    519-646-6332    janet.pope@sjhc.london.on.ca   
Principal Investigator: Janet E Pope         
Sub-Investigator: Tatiana Nevskaya         
Sub-Investigator: Louise Vanderhoek         
Sub-Investigator: Sara Hewitt         
Sponsors and Collaborators
Lawson Health Research Institute
Seattle Genetics, Inc.
Investigators
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Principal Investigator: Janet E Pope 1University of Western Ontario, Division of Rheumatology, St. Joseph's Health Care, London, Ontario, Canada

Publications:
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Responsible Party: Janet Pope, Head of Rheumatology, Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT03198689    
Other Study ID Numbers: BV201708
First Posted: June 26, 2017    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Janet Pope, Lawson Health Research Institute:
systemic sclerosis
scleroderma
brentuximab vedotin
CD30-directed antibody-drug conjugate
antirheumatic agents
antineoplastic agents
connective tissue diseases
skin diseases
immunologic factors
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs