Brentuximab Vedotin for Systemic Sclerosis

Recruiting in Palo Alto (17 mi)

Overseen by Janet E Pope, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Must be taking: Brentuximab vedotin

Must not be taking: Rituximab

Disqualifiers: Pulmonary hypertension, Cardiac disease, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used rituximab in the previous 4 months or have been immunized with a live vaccine less than 4 weeks before the trial starts.

How is the drug Brentuximab Vedotin different from other treatments for systemic sclerosis?

Brentuximab Vedotin is unique because it is an antibody-drug conjugate that targets CD30, a protein found on certain immune cells, and delivers a potent chemotherapy agent directly to these cells, which is different from other treatments that typically target different pathways or proteins in systemic sclerosis. ^{1 2 3 4 5}

Research Team

Janet E Pope, PhD

Principal Investigator

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

Eligibility Criteria

This trial is for patients with a severe form of scleroderma called diffuse cutaneous systemic sclerosis (dcSSc) who have previously been treated with Brentuximab vedotin but experienced a relapse. Participants must show worsening skin symptoms and be able to give informed consent.

Inclusion Criteria

I am capable of understanding and agreeing to the trial's procedures and risks.

My skin condition has worsened by 4 points since my last treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Brentuximab vedotin treatment for up to 48 weeks

48 weeks

Regular visits for assessments at 12, 24, 36, and 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Post-treatment monitoring for adverse events and outcomes

Open-label extension

Continuation of Brentuximab vedotin treatment for patients who relapsed after discontinuation

Long-term

Treatment Details

Interventions

• Brentuximab Vedotin (Monoclonal Antibodies)

Trial Overview The study is testing the safety and effectiveness of Brentuximab vedotin, an antibody-drug conjugate targeting CD30, in those who've had dcSSc worsen after stopping previous treatment with the same drug.

Participant Groups

Group I: Administration of Brentuximab vedotin Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

668

Recruited

424,000+

Roy Butler

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

Chief Executive Officer

PhD in Health Sciences

Dr. Cindy Hutnik

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

Chief Medical Officer

MD, PhD

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

Lead Sponsor

Trials

686

Recruited

427,000+

Dr. Alex Barron

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

Chief Medical Officer since 2023

MD from Western University

David Musyj

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

Chief Executive Officer

Physiotherapy degree

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

Lead Sponsor

Trials

678

Recruited

421,000+

Lisa Porter

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

Chief Medical Officer

PhD in Biomedical Sciences

Roy Butler

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

Chief Executive Officer

PhD in Health Sciences

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Dr. Michael Strong

Lawson Health Research Institute

Chief Medical Officer

MD

Roy Butler

Lawson Health Research Institute

Chief Executive Officer

PhD in Health Sciences

Seattle Genetics (now a wholly owned subsidiary of Pfizer)

Collaborator

Trials

1

Recruited

10+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Findings from Research

In a double-blind, placebo-controlled study, bermekimab, an IL-1α blocking monoclonal antibody, showed significant efficacy in treating systemic sclerosis (SSc), with 80% of treated patients meeting the primary endpoint compared to only 20% in the placebo group (p: 0.023).

The treatment notably improved lung function, as indicated by increased carbon monoxide lung diffusion capacity, and reduced levels of IL-1α and TNF in circulating mononuclear cells, suggesting a beneficial mechanism of action for bermekimab in SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized clinical trial of bermekimab treatment for clinical improvement of systemic sclerosis. Solomonidi, N., Vlachoyiannopoulos, PG., Pappa, M., et al.[2023]

In an open-label study of 8 patients with diffuse cutaneous systemic sclerosis (dc-SSc), rituximab effectively depleted B-cells and significantly improved skin sclerosis scores after 24 weeks (p<0.001).

Rituximab treatment also led to notable improvements in skin histopathology, including reduced collagen content and myofibroblast numbers, while being well tolerated with only two serious adverse events deemed unrelated to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Smith, V., Van Praet, JT., Vandooren, B., et al.[2022]

In a 26-week pilot study involving 16 patients with diffuse cutaneous systemic sclerosis (dcSSc), infliximab treatment did not result in significant improvements in skin scores, but there was a trend towards lower skin scores at 22 weeks and a notable reduction in collagen markers, indicating some stabilization of the disease.

While infliximab was generally safe with no deaths reported, 15% of adverse events were likely related to the treatment, and half of the patients discontinued due to issues, suggesting that future studies may need to consider additional immunosuppression to manage infusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Denton, CP., Engelhart, M., Tvede, N., et al.[2015]

Rituximab treatment in patients with diffuse systemic sclerosis (dSSc) showed significant improvements in lung function (FVC) and skin involvement (mRSS) over a follow-up period of up to 24 months, indicating its efficacy in managing this condition.

The safety profile of rituximab appears to be reasonable, comparable to its use in other autoimmune diseases, suggesting it can be a safe treatment option for patients with systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. Thiebaut, M., Launay, D., Rivière, S., et al.[2018]

In a phase I study involving 28 adults with systemic sclerosis (SSc), MEDI-551, a monoclonal antibody targeting B cells, was found to be safe and tolerable, with most treatment-emergent adverse events being mild or moderate.

The treatment led to a dose-dependent depletion of circulating B cells and plasma cells, and there was a potential clinical effect on skin symptoms, suggesting that MEDI-551 may be a promising disease-modifying therapy for SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. Schiopu, E., Chatterjee, S., Hsu, V., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized clinical trial of bermekimab treatment for clinical improvement of systemic sclerosis. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. [2015]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. [2019]