Clinical trial NCT05149768: Open Label Extension Study of Brentuximab Vedotin in Early dcSSc
Official title: An Open Label Extension Study of Brentuximab Vedotin Treatment in Active Diffuse Cutaneous Systemic Sclerosis (Diffuse Scleroderma)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Cutaneous Systemic Sclerosis
Keywords: systemic sclerosis
scleroderma
brentuximab vedotin
CD30-directed antibody-drug conjugate
antirheumatic agents
antineoplastic agents
skin diseases
immunologic factors
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Seattle Genetics (now a wholly owned subsidiary of Pfizer)
name: Pfizer
First posted: 2021-12-08
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Change in skin thickness measured by modified Rodnan Skin Score
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in skin thickness over time measured by modified Rodnan Skin Score
timeFrame: 12 weeks and 36 weeks
measure: Change in physician global assessment of disease activity
timeFrame: 12, 24, 36, and 48 weeks.
measure: Change in physician global assessment of disease severity
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in physician global assessment of disease damage
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in patient global assessment of health status
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in Scleroderma Health Assessment Questionnaire (SHAQ)
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in the diffusing capacity for carbon monoxide (pulmonary function)
timeFrame: 24 and 48 weeks*
measure: Change in Forced Vital Capacity (pulmonary function)
timeFrame: 24 and 48 weeks*
measure: Combined Response Index in diffuse cutaneous systemic sclerosis score (CRISS)
timeFrame: Baseline (week 0), and at 24, 48 weeks
measure: Change in serum concentrations C-Reactive Protein
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in serum concentrations of Erythrocyte Sedimentation Rate
timeFrame: 12, 24, 36, and 48 weeks
Other outcomes:
measure: Regimen-related toxicities
timeFrame: assessed for duration of treatment up to 48 weeks, and up to 12 weeks post-treatment
measure: Infectious complications
timeFrame: assessed for duration of treatment up to 48 weeks, and up to 1 month post-treatment
measure: Change in peripheral levels of T-cell activation marker - sIL-2R
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in peripheral levels of fibrillogenesis - amino terminal propeptide of type III collagen
timeFrame: 12, 24, 36, and 48 weeks
measure: Change in CD30-positive cell count (T-cell marker) in skin biopsies of involved forearm skin
timeFrame: Taken at Baseline (week 0), and 24, 48 weeks
Locations:
city: London
country: Canada
facility: Rheumatology Clinic, St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: University of Western Ontario, Division of Rheumatology, St. Joseph's Health Care, London, Ontario, Canada
name: Janet E Pope, PhD
role: PRINCIPAL_INVESTIGATOR
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