Open Label Extension Study of Brentuximab Vedotin in Early dcSSc

NCT ID: NCT05149768

Last Updated: 2024-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-14
• Study Completion Date: 2026-07-01

Brief Summary

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.

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). 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.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Administration of Brentuximab vedotin

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

Group Type: EXPERIMENTAL

Brentuximab vedotin

Intervention Type: DRUG

Dose 0.6mg/kg 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, mycophenolate mofetil (MMF, cellcept) and mycophenolic acid (myfortic)

Interventions

Brentuximab vedotin

Dose 0.6mg/kg 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, mycophenolate mofetil (MMF, cellcept) and mycophenolic acid (myfortic)

Intervention Type: DRUG

Other Intervention Names

ADCETRIS, SGN-35

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seattle Genetics (now a wholly owned subsidiary of Pfizer)

UNKNOWN

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Janet Pope

Head of Rheumatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Janet E Pope, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Rheumatology Clinic, St. Joseph's Health Care

London, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Janet E Pope, PhD

Role: CONTACT

Janet.Pope@sjhc.london.on.ca

519-646-6332

Amanda Philip

Role: CONTACT

Amanda.Philip@sjhc.london.on.ca

519-646-6000 ext. 61228

Facility Contacts

Janet E Pope

Role: primary

janet.pope@sjhc.london.on.ca

519-646-6332

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Other Identifiers

BV202108

Identifier Type: -

Identifier Source: org_study_id