Randomized, Placebo-Controlled, Phase 3 Trial of PI3Kδ Inhibitor Leniolisib for Activated PI3Kδ Syndrome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10450556" target="_blank" >RIV/00064203:_____/23:10450556 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/23:10450556
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f7blP2gi6A" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f7blP2gi6A</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2022018546" target="_blank" >10.1182/blood.2022018546</a>
Alternative languages
Result language
angličtina
Original language name
Randomized, Placebo-Controlled, Phase 3 Trial of PI3Kδ Inhibitor Leniolisib for Activated PI3Kδ Syndrome
Original language description
Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity with clinical manifestations including infections, lymphoproliferation, autoimmunity, enteropathy, bronchiectasis, increased risk of lymphoma, and early mortality. Hyperactive PI3Kδ signaling causes APDS and is selectively targeted with leniolisib, an oral, small molecule inhibitor of PI3Kδ. Here, 31 patients with APDS aged >=12 years were enrolled in a global, phase 3, triple-blinded trial and randomized 2:1 to receive 70-mg leniolisib or placebo twice daily for 12 weeks. Co-primary outcomes were differences from baseline in index lymph node size and in percentage of naïve B cells in peripheral blood, assessed as proxies for immune dysregulation and deficiency. Both primary outcomes were met: the difference in the adjusted mean change (95% CI) between leniolisib and placebo for lymph node size was -0.25 (-0.38, -0.12; P=0.0006; N=26) and for percentage of naïve B cells was 37.30 (24.06, 50.54; P=0.0002; N=13). Leniolisib reduced spleen volume compared to placebo (adjusted mean difference in 3-dimensional volume [cm3], -186; 95% CI, -297 to -76.2; P=0.0020) and improved key immune cell subsets. Fewer patients receiving leniolisib reported study treatment-related adverse events (mostly grades 1-2) compared to those receiving placebo (23.8% vs 30.0%). Overall, leniolisib was well tolerated and significant improvement over placebo was notable in the co-primary endpoints, reducing lymphadenopathy and increasing the percentage of naïve B cells, reflecting a favorable impact on the immune dysregulation and deficiency seen in patients with APDS. (Funded by DIR/NIAID, Novartis, and Pharming Group, NV; ClinicalTrials.gov identifier: NCT02435173.).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
1528-0020
Volume of the periodical
141
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
971-983
UT code for WoS article
000954475800001
EID of the result in the Scopus database
2-s2.0-85146126135