Approved psoriasis drug apremilast to be tested in severe EBS patients
Phase 2 trial will track number of new blister cases in week before site visits
Researchers at four centers in France will evaluate the safety and effectiveness of apremilast, an approved oral psoriasis therapy, in children and adults with severe epidermolysis bullosa simplex (EBS) in an open-label Phase 2 clinical trial.
Dubbed EBULO (NCT06509984), the study will test apremilast — currently sold as Otezla for the treatment of plaque psoriasis, psoriatic arthritis, and oral ulcers in Behçet’s disease — in up to 20 patients with severe EBS, ages 6 and older. Clinical sites include two centers in Paris, and one each in Nice and Toulouse.
“The trial will provide high-quality evidence to inform clinical management in children and adults, supporting future improvements in first-line care for this rare condition,” researchers wrote.
A detailed protocol was published in BMJ Open, under the title “Multicentre phase II open study assessing the efficacy and safety of apremilast in children and adults with epidermolysis bullosa simplex generalised: study protocol for the EBULO study.”
EBS caused by mutations in either of 2 key genes
Epidermolysis bullosa (EB) is a group of rare disorders characterized by skin that is fragile and easily tears, resulting in fluid-filled blisters. Blistering can also occur within the body, such as in the mucous membranes that surround organs and openings, including the mouth.
EBS, the most common form of EB, is caused by mutations in either the KRT5 or KRT14 genes. Because these genes encode proteins crucial to the structural integrity of the outermost skin layers, or epidermis, the skin can easily tear with friction or minor trauma.
Usually starting in infancy or early childhood, EBS can present as mild blistering limited to the hands and feet (localized EBS) or as more widespread, severe blistering accompanied by internal wounds and complications such as infections (severe EBS).
Currently, there is no cure for EBS. Disease management encompasses avoiding activities that damage the skin, administering symptomatic therapies, providing wound care, and controlling infections.
Recent studies have suggested that skin tears caused by friction or minor trauma alone don’t fully explain the progression of the disease, and that inflammation may play a role.
Previous work by researchers in France revealed that a specific class of immune T cells — known as Th17 cells — may drive inflammation in severe EBS. Twice-daily treatment with apremilast, a drug that targets Th17 cells, markedly reduced the number of blisters over the course of a month in adults with severe EBS.
Eligible participants must present with at least 4 new blisters per day
Building on these promising findings, investigators launched EBULO to further test apremilast in about 20 children and adults, ages 6 and older, with severe EBS. Eligible participants are those who weigh at least 15 kg (33 lbs) and present with at least four new blisters per day. The study is an open-label design, meaning participants are aware of the treatment they receive.
Participants will receive twice-daily apremilast at a dose adjusted for age and body weight for a period of eight weeks. Treatment will be paused for four weeks and then restarted for another eight weeks up to week 20, or nearly five months. All patients will receive local wound dressings as needed and participate in therapeutic educational sessions.
EBULO’s primary efficacy endpoint is the number of new blister cases per day during the week before each site visit, which 10 patients and caregivers identified as the most relevant outcome for determining treatment effectiveness in EBS.
The number of new blisters will be counted over the entire body surface, including the scalp, before daily blister piercing and dressing care. The researchers will conduct these assessments before treatment and at weeks 4, 8, 12, and 20.
In addition to safety and tolerability, disease severity will be gauged by both patients and clinicians using the iscor-EB scale, a validated score for EB patients, along with the Physician Global Assessment. Itch and pain will be rated on a 0-10 numeric scale, and quality of life will be assessed using the Dermatology Life Quality Index for both adults and children. For severe EBS, the new iscareEB score will also be used.
The study is being funded by Dystrophic Epidermolysis Bullosa Research Association (DEBRA) in the U.K. and supported by DEBRA France. Final EBULO results will be posted on the clinical trials website, according to the researchers.
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