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The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. Interim results demonstrated strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 post-dosing. Here we report that these responses with PHH-1V are sustained up to 6 months, including in participants over 65 years, despite their smaller sample size. The PHH-1V booster was non-inferior in eliciting neutralizing antibodies for SARS-CoV-2 Omicron XBB.1.5 variant compared to BNT162b2 after 6 months. No severe COVID-19 cases occurred in any group, and mild cases were similar (50.4 % for PHH-1V vs. 47.8 % for BNT162b2). While both groups may have reached comparable immunity levels, these findings suggest that the PHH-1V vaccine provides long-lasting immunity against various of SARS-CoV-2 variants. ClinicalTrials.gov Identifier: NCT05142553., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J Blanco has received institutional grants from HIPRA, Grifols, Nesapor Europe and MSD. Outside of this work he is the CEO and founder of AlbaJuna Therapeutics, S.L. A Soriano has received grants from Pfizer and Gilead Sciences and honoraria for lectures for Pfizer, MSD, Gilead Sciences, Shionogi, Angelini, Roche and Menarini. N Izquierdo-Useros declares institutional grants from HIPRA, Pharma Mar, Grifols, and Amassence. J R Arribas has received honoraria for lectures and advisory boards from Janssen, Gilead, MSD, Lilly, Roche, and Pfizer. S Otero-Romero has received speaking and consulting honoraria from Genzyme, Biogen-Idec, Novartis, Roche, Excemed and MSD. J G Prado declares institutional grants from HIPRA and Grifols. AM Borobia is principal investigator of clinical trials sponsored by GlaxoSmithKline, Daiichi-Sankyo and Janssen, outside of the submitted work. J Molto has received honoraria for lectures and advisory boards from Johnson & Johnson, Gilead, and MSD. X Martínez-Gómez has received speaking and consulting honoraria from GSK, Pfizer, and AstraZeneca. J Corominas, C Garriga, A Prenafeta, A Moros, M Cañete, A Barreiro, L González-González, L Madrenas, I Güell, T Prat, E Torroella and L Ferrer are employees of HIPRA. Some of these authors may have shares of HIPRA. Several patent applications have been filed by HIPRA SCIENTIFIC S.L.U. and Laboratorios HIPRA, S.A. on different SARS-CoV-2 vaccine candidates and SARS-CoV-2 subunit vaccines, including the novel recombinant RBD fusion heterodimer PHH-1V. A Barreiro, A Prenafeta, L González-González, L Ferrer, T Prat and C Garriga are the inventors of these patent applications., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This was a Phase I, randomized, double-blinded, three-arm, single-dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU-reference] and United States [US-reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC 0-last ); and maximum observed serum concentration (C max ). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC 0-∞ ), time to reach maximum observed concentration, clearance, terminal phase half-life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. C max was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half-live across treatment arms. Systemic exposure of MB09 (AUC 0-last and C max ) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C-terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment-emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products., (© 2024 mAbxience Research SL. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background Aims: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA - memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment., Methods: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 10 6 /kg CD45RA - memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA - memory T cells and the most frequent human leukocyte antigen typing in the Spanish population., Results: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events., Conclusions: Adoptive cell therapy with off-the-shelf CD45RA - memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia., Trial Registration: NCT04578210., Competing Interests: Declaration of Competing Interest CF, AP-M and BS filed patent PCT/EP2021/076516 on Memory T cells as adoptive cell therapy for viral diseases. All other authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Background: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation., Methods: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected., Results: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib., Conclusions: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials., Clinical Trials Registration: EudraCT: 2020-001156-18., Competing Interests: Potential conflicts of interest. P. R. has received grant support and honoraria from Gilead and MSD; consulting fees from AbbVie SL; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from ViiV and Gilead Sciences; and support for attending meetings and/or travel from AbbVie and GSK (ViiV). J. V. has received scholarships and honorarium as speaker for Gilead Sciences. M. S. has received honoraria from Gilead; has developed educational material for MSD and ViiV Healthcare; and has served on advisory boards for MSD and Gilead. A. M. B. reports grants or contracts from GSK, Moderna, and Janssen (paid to institution); advisory fees from Janssen and Pfizer (paid to author); participation on a data and safety monitoring board (DSMB) for Pfizer, Janssen, and Medical Developments International (paid to author); payment or honoraria for lectures, presentations, manuscript writing, or educational events from Gilead and Pfizer (paid to author); and speaker’s fees from Janssen (paid to author). J. R. A. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Merck (paid to author); support for attending meetings and/or travel from MSD (paid to author); and consulting fees, advisory fees, and speaker’s fees from Gilead, Merck, Pfizer, Sobi, GSK, MSD, Serono, Lilly, and Roche (paid to author); he is also a member of the Infectious Diseases and Clinical Microbiology Society COVID-19 treatment guidelines. A. G. L. reports payment or honoraria for presentation from Gilead Sciences, and support for attending meetings and/or travel from Angelini Pharma España. A. J. C. reports grants or contracts from ISCIII, Ministry of Innovation and Science of Spain (PI21/01507, PI18/00136, CM19/00243, ICI21/00065), and Vaccelerate (Clinical trial name: EU-Covat-1 Aged); payment or honoraria for a course on clinical investigation (paid to institution) from AbbVie, and participation on a DSMB or advisory board for AMR Insights (paid to institution). C. G. reports consulting fees, participation on a DSMB or advisory board, and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Amgen, Daiichi Sankyo, Ferrer, and Sanofi; and support for attending meetings and/or travel from Sanofi and Ferrer. L. S. reports grants or contracts from Novartis and Boehringer, and support for attending meetings and/or travel from Novartis. M. R.-M. reports support for attending meetings and/or travel from Roche Farma SA. M. N. M. reports support for attending meetings and/or travel and payment/honoraria for presentations and educational events from Gilead. M. V. A. reports grants or contracts from Gilead and ViiV (paid to institution); payment or honoraria for lectures and educational events for Gilead and Janssen (paid to author and institution); payment or honoraria for educational events from ViiV and MSD (paid to institution); and support for attending meetings and/or travel from Angelini, Gilead, and Janssen (paid to author). P. G.-R. P. reports support for attending meetings and/or travel from Gilead and Angelini. P. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Sanofi (paid to author). R. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead, ViiV, Merck Sharp & Dohme, and Theratechnologies (paid to author); payment for expert testimony from Gilead and ViiV (paid to author); support for attending meetings and/or travel from Gilead and Janssen (paid to author); and participation on a DSMB or advisory board for ViiV (paid to author). S. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Pfizer, Gilead, Roche, Sobi, and MSD (paid to author), and participation on DSMBs or advisory boards for Pfizer, Gilead, and MSD (paid to author). V. E. reports consulting fees from Gilead, Janssen, and MSD (paid to author); payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead and Janssen (paid to author); support for attending meetings and/or travel from Gilead (paid to author); and participation on DSMBs or advisory boards for Gilead, Janssen, and Synairgen (paid to author). None of the listed potential conflicts are related to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm ( p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm ( p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% ( n = 14) in the melatonin versus 1.4% ( n = 2) in the placebo arm ( p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.