Brentuximab Vedotin for Systemic Sclerosis

Overseen By Janet E Pope, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Brentuximab Vedotin to determine its safety and effectiveness for people with diffuse cutaneous systemic sclerosis, a condition that causes skin hardening and thickening. The focus is on patients whose condition worsened after stopping the drug in an earlier study. Participants should have this specific type of scleroderma and have experienced a significant increase in skin problems after previously using Brentuximab Vedotin. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

Is there any evidence suggesting that Brentuximab Vedotin is likely to be safe for humans?

Research shows that brentuximab vedotin, a treatment under study for systemic sclerosis (a condition affecting the skin and other organs), has been evaluated for safety and effectiveness. In earlier studies with patients who had severe cases, brentuximab vedotin was generally well-tolerated. Some studies have found that it might help improve skin symptoms. However, like most treatments, some side effects were reported, including low blood cell counts and mild reactions during infusion. Since this treatment is already approved for other conditions, some information about its safety is available. However, individual reactions vary, highlighting the importance of this study to gather more specific safety data for people with systemic sclerosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic sclerosis?

Unlike the standard treatments for systemic sclerosis, which often focus on managing symptoms through immunosuppressants and anti-inflammatory drugs, Brentuximab Vedotin offers a novel approach by targeting CD30-positive cells. This drug is an antibody-drug conjugate, combining an antibody that specifically binds to CD30 with a potent anticancer agent. Researchers are excited about Brentuximab Vedotin because this targeted approach could potentially modify the disease process itself, rather than just alleviating symptoms, providing a more effective treatment for patients with this challenging condition.

What evidence suggests that Brentuximab Vedotin might be an effective treatment for systemic sclerosis?

Research shows that brentuximab vedotin, which participants in this trial will receive, may help treat diffuse cutaneous systemic sclerosis (dcSSc), a type of scleroderma affecting the skin. Studies have found that this treatment improved the modified Rodnan Skin Score (mRSS), which measures skin thickness, in patients with severe dcSSc. Brentuximab vedotin targets a protein called CD30 on certain cells, potentially reducing inflammation and the thickening and scarring of tissue. Early findings suggest the drug can be effective for those whose condition has returned after previous treatment. While more research is needed, these early results offer hope for people dealing with this challenging condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Janet E Pope, PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin

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.

How Is the Trial Designed?

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

Brentuximab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Primary cutaneous anaplastic large cell lymphoma
• CD30-expressing mycosis fungoides
• Peripheral T-cell lymphoma

Approved in European Union as Adcetris for:

• Hodgkin lymphoma
• Systemic anaplastic large cell lymphoma
• Cutaneous T-cell lymphoma

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+

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

Lead Sponsor

Trials

686

Recruited

427,000+

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

Lead Sponsor

Trials

678

Recruited

421,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

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

Published Research Related to This Trial

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]

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]

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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38652570/

Brentuximab vedotin for skin involvement in refractory ... We explored the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03222492

NCT03222492 | Brentuximab Vedotin for Systemic Sclerosis The present study will be a dose-escalation safety trial of brentuximab vedotin, a drug-antibody conjugate approved for the treatment of lymphoma and targeted ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11781570/

Brentuximab vedotin compared with historical controls for ... In conclusion, brentuximab vedotin improved the mRSS in patients with severe dcSSc. In this exploratory analysis comparing the results to matched historic ...

4. academic.oup.com academic.oup.com/rheumatology/article/64/3/1476/7656783

Brentuximab vedotin for skin involvement in refractory diffuse ... We explored the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03198689?term=AREA%5BConditionSearch%5D(%22Scleroderma,%20Diffuse%22)&rank=2

Brentuximab Vedotin in Early Diffuse Cutaneous Systemic ... The purpose of this study is to assess feasibility, safety and preliminary efficacy of Brentuximab vedotin (Adcetris), a CD30-directed antibody-drug conjugate, ...

6. acrabstracts.org acrabstracts.org/abstract/dose-escalation-safety-study-of-brentuximab-vedotin-for-diffuse-cutaneous-systemic-sclerosisclinical-results-and-mechanistic-analysis-of-skin-and-peripheral-blood-mononuclear-cells/

Dose Escalation Safety Study of Brentuximab Vedotin for ... Although the results were limited by a small sample size, the data suggest improvement in mRSS with BV and show reduced frequencies of several activated ...