Brentuximab vedotin is a medicine being investigated to possibly treat people with systemic scleroderma, an autoimmune disease caused by an overactive immune system that mistakenly attacks healthy tissues, leading to scarring and thickening of the connective tissue of multiple organs.
Brentuximab vedotin, under the brand name of Adcetris (developed and marketed by Seattle Genetics), is approved to treat certain patients with classical Hodgkin’s lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL).
How brentuximab vedotin works
Brentuximab vedotin is an antibody, a protein designed to bind to a specific target, attached by a linker to a substance called monomethyl auristatin E (MMAE), a synthetic agent that blocks cell division.
The antibody portion of the medicine specifically targets a protein called CD30 that is found on the surface of activated immune cells and thought to be involved in the development of systemic scleroderma. Once bound to CD30, brentuximab vedotin is taken inside the cell where the linker is cleaved, releasing the MMAE part, which stops the cells from dividing and producing more autoimmune cells. In this way, the medicine is expected to reduce the number of CD30-positive immune cells in the body, improving disease symptoms.
Brentuximab vedotin in clinical trials
A placebo-controlled, dose-escalation Phase 1/2 trial (NCT03222492), called BRAVOS, is now evaluating the safety and tolerability of brentuximab vedotin in 20 to 25 patients with diffuse systemic scleroderma and on a stable background immunosuppressive therapy.
During the trial, patients will be given ascending doses of the medicine (0.6 mg per kg of weight, 1.2 mg per kg, and 1.8 mg per kg) or placebo every three weeks for 21 weeks, as an injection into the bloodstream (intravenous administration). Treatment phase will be followed by examinations in visits at weeks 24, 28, 36, and 48.
As safety and tolerability are primary trial goals, researchers will be recording the proportion of patients experiencing at least one grade 3 (severe) or higher adverse event from first dose though to week 48 of follow-up. Changes in skins scores will also be measured as an exploratory outcome.
The trial is now enrolling at nine sites across the U.S., and is expected to be completed in September 2020.
An open-label Phase 2 pilot clinical trial (NCT03198689), not yet recruiting, will further evaluate the safety as well as the efficacy of brentuximab vedotin, again in addition to standard-of-care medications, in about 10 diffuse systemic scleroderma patients with early or active disease.
It primary endpoint will be the treatment’s effectiveness in improving skin fibrosis, as measured by changes in the modified Rodnan skin score (MRSS), a measure of skin thickness, from the study start to month 12. Several other measures, like the health assessment questionnaire disability index (HAQ-DI), a questioner where patients report the amount of difficulty experienced when performing some activities; inflammatory markers; and the combined response index in systemic scleroderma (CRISS) will also be used to assess the potential effects of the treatment.
The trial plans to start enrolling eligible patients at its one site in Ontario, Canada, beginning in September 2018.
Side effects associated with the brentuximab vedotin as a cancer treatment include numbness and tingling in the fingers and toes, nausea, vomiting, fatigue, diarrhea, high temperature, rashes, headache, back and muscle pain, loss of appetite, and breathing problems.
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