Prophylactic (preventative) treatment with Cinryze reduced the number and severity of attacks in young children with hereditary angioedema (HAE), without significant adverse events, a Phase 3 trial shows.
The study, “A Randomized Trial of human C1 inhibitor prophylaxis in children with hereditary angioedema,” was published in Pediatric Allergy and Immunology.
HAE is a rare genetic disorder characterized by sudden and recurrent episodes of swelling in the deeper layers of the skin, the upper airway, and the gastrointestinal tract.
The disease is caused by genetic mutations in the SERPING1 gene, leading to lower levels of C1-inhibitor (C1-INH), in the case of HAE type 1, or to a dysfunctional C1-INH whose levels remain normal or elevated in the case of HAE type 2.
Shire‘s Cinryze is one of the two C1-INH replacement medications currently approved by the U.S. Food and Drug Administration (FDA) for the long-term prophylactic treatment of patients with HAE. Its first approval as a preventative therapy was in 2008, and was restricted to adults and teenagers with HAE.
Then, a decade later, the FDA extended the approval to children age 6 and older, largely based on promising findings from a multi-center, randomized, single-blind, crossover Phase 3 clinical trial (NCT02052141) designed to assess the safety and efficacy of Cinryze in young children with HAE.
After reporting the first interim results of the trial, researchers now described the complete findings of the study involving 12 children with HAE ages 6–11.
Children participating in the trial received 500 or 1,000 units of Cinryze twice a week for 12 weeks. They then switched to the other dose regimen for the same period of time.
The trial’s primary endpoint was to assess the change in the number of monthly HAE attacks from baseline until the end of the 12-week treatment period. Secondary endpoints included assessing the severity of HAE attacks, treatment safety, tolerability, and impact on health-related quality of life (HRQoL). HRQoL was measured using the EuroQol 5‐dimensional descriptive system youth version and visual analog scale (EQ‐VAS).
Results showed that, on average, children treated with 500 and 1,000 units had a reduction of 71.1% and 84.5% in the number of monthly attacks, respectively. The number of acute attacks and the severity of attacks were also significantly reduced after 12 weeks of treatment.
“Overall, prophylaxis with 1,000 units C1-INH was statistically superior to 500 units C1-INH in reducing [monthly normalized number of angioedema attacks] and provided better outcomes, but some patients also had excellent results with the lower dose,” researchers said.
The mean change in the EQ-VAS score from baseline to the ninth week of treatment reflected significant improvements in HRQoL for children treated with 500 and 1,000 units of Cinryze (score difference of 10.4 and 21.6, respectively). A change in EQ-VAS score greater than seven is considered clinically meaningful.
The most common treatment-emergent adverse events reported in the trial included fatigue (16.7%), irritability (16.7%), diarrhea (8.3%), skin redness (8.3%), and itchiness (8.3%). No serious adverse events leading to treatment discontinuation occurred.
“C1‐INH prophylaxis was effective, safe, and well-tolerated in children aged 6‐11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1‐INH,” the scientists said.