Laboratory safety from a randomized 16-week phase III study of dupilumab in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Background and Objective: Previous studies of dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents, and severe atopic dermatitis in children aged 6 to < 12 years demonstrate no clinically important changes in laboratory parameters. The objective of this study was to assess laboratory outcomes in children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis treated with dupilumab. Methods: In this randomized, placebo-controlled, phase III trial of dupilumab, 161 children aged 6 months to < 6 years with moderate-to-severe atopic dermatitis were enrolled from 31 sites in Europe and North America and randomized 1:1 to receive subcutaneous placebo or dupilumab (5 kg to < 15 kg: 200 mg; 15 kg to < 30 kg: 300 mg) every 4 weeks plus topical corticosteroids for 16 weeks. Hematology, serum chemistry, and urinalysis assessments were analyzed on blood and urine samples collected at screening and weeks 4 and 16; descriptive statistics are provided. Results: No clinically meaningful changes in laboratory parameters were observed. While two cases of eosinophilia and one case each of neutropenia and leukocytosis were reported as treatment-emergent adverse events in the dupilumab plus topical corticosteroids group, these events were not associated with clinical symptoms and did not lead to treatment discontinuation or study withdrawal. Conclusions: These results suggest that routine laboratory monitoring of children aged 6 months to < 6 years treated with dupilumab plus topical corticosteroids is not required. Limitations of this study include short study duration, and exclusion of patients with abnormalities in laboratory test results at screening. Clinical Trial Registration: ClinicalTrials.gov: NCT03346434, part

Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 &lt;sup&gt;+&lt;/sup&gt; and CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. Co-culturing CD4 &lt;sup&gt;+&lt;/sup&gt; with autologous CD8 &lt;sup&gt;+&lt;/sup&gt; T cells from ART-suppressed HIV &lt;sup&gt;+&lt;/sup&gt; donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. This trispecific antibody mediates CD4 &lt;sup&gt;+&lt;/sup&gt; and CD8 &lt;sup&gt;+&lt;/sup&gt; T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection

Energy scan of the e+e−→hb(nP)π+π−e^+e^- \to h_b(nP)\pi^+\pi^- (n=1,2)(n=1,2) cross sections and evidence for the Υ(11020)\Upsilon(11020) decays into charged bottomonium-like states

Using data collected with the Belle detector in the energy region of the $\Upsilon(10860)$ and $\Upsilon(11020)$ resonances we measure the $e^+e^- \to h_b(nP)\pi^+\pi^-$ $(n=1,2)$ cross sections. Their energy dependences show clear $\Upsilon(10860)$ and $\Upsilon(11020)$ peaks with a small or no non-resonant contribution. We study resonant structure of the $\Upsilon(11020) \to h_b(nP)\pi^+\pi^-$ transitions and find evidence that they proceed entirely via intermediate charged bottomonium-like states $Z_b(10610)$ and/or $Z_b(10650)$ (with current statistics we can not discriminate hypotheses of one or two intermediate states).Using data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider, we measure the energy dependence of the e+e-→hb(nP)π+π- (n=1, 2) cross sections from thresholds up to 11.02 GeV. We find clear ϒ(10860) and ϒ(11020) peaks with little or no continuum contribution. We study the resonant substructure of the ϒ(11020)→hb(nP)π+π- transitions and find evidence that they proceed entirely via the intermediate isovector states Zb(10610) and Zb(10650). The relative fraction of these states is loosely constrained by the current data: The hypothesis that only Zb(10610) is produced is excluded at the level of 3.3 standard deviations, while the hypothesis that only Zb(10650) is produced is not excluded at a significant level.Using data collected with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider, we measure the energy dependence of the $e^+e^- \to h_b(nP)\pi^+\pi^-$ $(n=1,2)$ cross sections from thresholds up to $11.02\,$GeV. We find clear $\Upsilon(10860)$ and $\Upsilon(11020)$ peaks with little or no continuum contribution. We study the resonant substructure of the $\Upsilon(11020) \to h_b(nP)\pi^+\pi^-$ transitions and find evidence that they proceed entirely via the intermediate isovector states $Z_b(10610)$ and $Z_b(10650)$. The relative fraction of these states is loosely constrained by the current data: the hypothesis that only $Z_b(10610)$ is produced is excluded at the level of 3.3 standard deviations, while the hypothesis that only $Z_b(10650)$ is produced is not excluded at a significant level

Measurements of branching fraction and CPCP asymmetry of the Bˉ0(B0)→KS0K∓π±\bar{B}^{0}(B^{0})\to K^{0}_{S}K^{\mp}\pi^{\pm} decay at Belle

International audienceWe report the measurement of the branching fraction and $CP$ asymmetry for the $\bar{B}^{0}(B^{0})\to K^{0}_{S}K^{\mp}\pi^{\pm}$ decay. The analysis is performed on a data sample of 711 $\rm{fb}^{-1}$ collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^{+}e^{-}$ collider. We obtain a branching fraction of $(3.60\pm0.33\pm0.15)\times10^{-6}$ and an $\mathcal{A}_{CP}$ of $(-8.5\pm8.9\pm0.2)\%$, where the first uncertainties are statistical and the second are systematic. Hints of peaking structures are also observed in the differential branching fraction as functions of Dalitz variables