Abstract | BACKGROUND: METHODS: In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile. RESULTS: Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (≥190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment. CONCLUSIONS:
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Authors | Barbara K Burton, Manisha Balwani, François Feillet, Ivo Barić, T Andrew Burrow, Carmen Camarena Grande, Mahmut Coker, Alejandra Consuelo-Sánchez, Patrick Deegan, Maja Di Rocco, Gregory M Enns, Richard Erbe, Fatih Ezgu, Can Ficicioglu, Katryn N Furuya, John Kane, Christina Laukaitis, Eugen Mengel, Edward G Neilan, Scott Nightingale, Heidi Peters, Maurizio Scarpa, K Otfried Schwab, Vratislav Smolka, Vassili Valayannopoulos, Marnie Wood, Zachary Goodman, Yijun Yang, Stephen Eckert, Sandra Rojas-Caro, Anthony G Quinn |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 373
Issue 11
Pg. 1010-20
(Sep 10 2015)
ISSN: 1533-4406 [Electronic] United States |
PMID | 26352813
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cholesterol, HDL
- Cholesterol, LDL
- Alanine Transaminase
- Sterol Esterase
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Topics |
- Adolescent
- Adult
- Aged
- Alanine Transaminase
(blood)
- Biopsy
- Child
- Child, Preschool
- Cholesterol, HDL
(blood)
- Cholesterol, LDL
(blood)
- Double-Blind Method
- Dyslipidemias
(drug therapy, genetics)
- Female
- Humans
- Liver
(drug effects, pathology)
- Male
- Middle Aged
- Sterol Esterase
(adverse effects, pharmacology, therapeutic use)
- Wolman Disease
(blood, drug therapy)
- Young Adult
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