Brentuximab Vedotin in Early Diffuse Cutaneous Systemic Sclerosis

NCT03198689 | Completed Phase 2 FDA Drug

• 1 other identifier: BV201708
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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).

Conditions

Diffuse Cutaneous Systemic Sclerosis

Keywords

systemic sclerosis; scleroderma; brentuximab vedotin; CD30-directed antibody-drug conjugate; antirheumatic agents; antineoplastic agents; connective tissue diseases; skin diseases; immunologic factors

Outcome Measures

Primary Outcomes (1)

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

  12 months

Secondary Outcomes (8)

• Change in mRSS

  3, 6 and 9 months

• CRISS score >20%

  6 months

• Change in FVC, %

  6 and 12 months

• Change in DLCO, %

  6 and 12 months

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

  3,6,9 and 12 months

Other Outcomes (9)

• Change in blood levels of soluble CD30

  3,6,9 and 12 months

• Change in serum levels of sIL-2R

  3,6,9 and 12 months

• Change in serum levels of aminoterminal propeptide of type III collagen

  3,6,9 and 12 months

Study Arms (1)

Administration of Brentuximab vedotin

EXPERIMENTAL

Maximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous use

Drug: Brentuximab Vedotin

Interventions

Brentuximab Vedotin DRUG

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).

Also known as: ADCETRIS, SGN-35

Administration of Brentuximab vedotin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Seagen Inc.: collaborator

Study Sites (1)

Rheumatology Clinic, St. Joseph's Health Care

London, Ontario, N6A 4V2, Canada

Location

Related Publications (7)

• 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 BACKGROUND

• 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.

  PMID: 25371098 BACKGROUND

• 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.

  PMID: 7562757 BACKGROUND

• 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.

  PMID: 16331791 BACKGROUND

• 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.

  PMID: 8235663 BACKGROUND

• 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.

  PMID: 16484228 BACKGROUND

• 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.

  PMID: 38652570 DERIVED

MeSH Terms

Conditions

Scleroderma, Diffuse; Scleroderma, Systemic; Connective Tissue Diseases; Skin Diseases

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Janet E Pope

  University of Western Ontario, Division of Rheumatology, St. Joseph's Health Care, London, Ontario, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Rheumatology

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 26, 2017
• Study Start: May 7, 2019
• Primary Completion: June 7, 2023
• Study Completion: August 28, 2023
• Last Updated: October 4, 2023

Record last verified: 2023-10

Locations

CA (1)