Brentuximab Vedotin in Early Diffuse Cutaneous Systemic Sclerosis

Phase 2

Completed

• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Interventions: Drug: Brentuximab Vedotin

• Registration Number: NCT03198689
• Lead Sponsor: 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).

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.

Study Timeline

• Study First Submitted: 2017-06-14
• Study First Submitted QC: 2017-06-22
• Study First Posted: 2017-06-26
• Study Start: 2019-05-07
• Primary Completion: 2023-06-07
• Study Completion: 2023-08-28
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of Brentuximab vedotin	Brentuximab Vedotin	Maximum duration of treatment: 48 weeks Maximum dose allowed: 0.6 mg/kg Route of administration: intravenous use

Primary Outcome Measures

Name	Time	Method
Change in skin thickness measured by modified Rodnan Skin Score (mRSS)	12 months

Secondary Outcome Measures

Name	Time	Method
Change in FVC, %	6 and 12 months
CRISS score >20%	6 months
Change in mRSS	3, 6 and 9 months
Change in DLCO, %	6 and 12 months
Change in SHAQ	3,6,9 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
Change in patient global assessment of health status (VAS 0 to 10)	3,6,9 and 12 months
Change in Health Transition score	3,6,9 and 12 months

Trial Locations

Locations (1)

Rheumatology Clinic, St. Joseph's Health Care; 🇨🇦 London, Ontario, Canada