Open Label Extension Study of Brentuximab Vedotin in Early dcSSc

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.

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.

Inclusion Criteria:

1. 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:
2. Worsening mRSS of ≥ 4 points as compared to mRSS score at the end of treatment visit (week 48) in the initial study (BV201708).
3. Able to give informed consent.

Exclusion Criteria:

1. Poor pulmonary function (FVC<40% and/or DLCO<30%).

2. Pregnancy, breast feeding or child bearing potential without practicing highly effective 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).

7. Active tuberculosis (TB) infection.

8. Active viral infection with viral replication of hepatitis B or C virus.

9. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, pancreatic, hematological, 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 <2.0 x 109/L
    • Hemoglobin <85 g/L
    • Platelet count < 100 x 109/L
    • AST/SGOT or ALT/SGPT >2.0 UNL

14. Participation in another clinical trial within six weeks before randomization in this study, with the exception of continuation from the initial study BV201708.

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. Current or history of progressive multifocal leukoencephalopathy (PML).