biostudies-literatureUnknown28(10)Feigin AVaccinex, Inc. Internal ResearchSIGNAL is a multicenter, randomized, double-blind, placebo-controlled phase 2 study (no. NCT02481674) established to evaluate pepinemab, a semaphorin 4D (SEMA4D)-blocking antibody, for treatment of Huntington's disease (HD). The trial enrolled a total of 265 HD gene expansion carriers with either early manifest (EM, n = 179) or late prodromal (LP, n = 86) HD, randomized (1:1) to receive 18 monthly infusions of pepinemab (n = 91 EM, 41 LP) or placebo (n = 88 EM, 45 LP). Pepinemab was generally well tolerated, with a relatively low frequency of serious treatment-emergent adverse events of 5% with pepinemab compared to 9% with placebo, including both EM and LP participants. Coprimary efficacy outcome measures consisted of assessments within the EM cohort of (1) a two-item HD cognitive assessmNature medicine2183-2193https://www.ebi.ac.uk/biostudies/studies/S-EPMC9361919biostudies-literaturePepinemab antibody blockade of SEMA4D in early Huntington's disease: a randomized, placebo-controlled, phase 2 trial.PMC9361919Siemers ERosas HDGoldstein JDuker AKostyk SSeeberger LMcFarland NKieburtz KDLaFaver KBoyd JElmer LStimming EFKamholz JNelson ACorey-Bloom JFrank SBang JMcDonell KHuntington Study Group SIGNAL investigatorsOakes DGoas CFeigin AEvans EELin YHZauderer MLeonard JEFactor SWojcieszek JSuchowersky OTesta CKowarski LSmith ESChouinard SScott BManber RWalters KAMarder KDayalu PRacette BGeshwind MSamii AWalker FMishra VKayson EBarbano RReader AFisher TLAnderson KClaassen DSung VRaymond LADean MfalsePepinemab antibody blockade of SEMA4D in early Huntington's disease: a randomized, placebo-controlled, phase 2 trial.SIGNAL is a multicenter, randomized, double-blind, placebo-controlled phase 2 study (no. NCT02481674) established to evaluate pepinemab, a semaphorin 4D (SEMA4D)-blocking antibody, for treatment of Huntington's disease (HD). The trial enrolled a total of 265 HD gene expansion carriers with either early manifest (EM, n = 179) or late prodromal (LP, n = 86) HD, randomized (1:1) to receive 18 monthly infusions of pepinemab (n = 91 EM, 41 LP) or placebo (n = 88 EM, 45 LP). Pepinemab was generally well tolerated, with a relatively low frequency of serious treatment-emergent adverse events of 5% with pepinemab compared to 9% with placebo, including both EM and LP participants. Coprimary efficacy outcome measures consisted of assessments within the EM cohort of (1) a two-item HD cognitive assessm2022-01-01T00:00:00Z2022 Oct2026-05-09T19:29:09.931Z2025-02-19T03:23:42.197ZS-EPMC93619193594137310.1038/s41591-022-01919-8