2892. Safety and Immunogenicity of mRNA-1647, an mRNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results of a Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Finding Trial
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC10677300 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Dengue is a mosquito-borne viral disease that is endemic in India. We evaluated the immunogenicity and safety of recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) in Indian adults. In this observer-blind, randomized, placebo-controlled, Phase II study, adults aged 18-45 years were randomized 2:1 to receive CYD-TDV or placebo at 0, 6 and 12 months in sub-cutaneous administration. Immunogenicity was assessed using a 50% plaque reduction neutralization test (PRNT50) at baseline and 28 days after each study injection. 189 participants were enrolled (CYD-TDV [n = 128]; placebo, [n = 61]). At baseline, seropositivity rates for dengue serotypes 1, 2, 3 and 4 ranged from 77.0% to 86.9%. Seropositivity rates for each serotype increased after each CYD-TDV injection with a more pronounced increase after the first injection. In the CYD-TDV group, geometric mean titres (GMTs) were 2.38 to 6.11-fold higher after the third injection compared with baseline but remained similar to baseline in the placebo group. In the CYD-TDV group, the GMTs were 1.66 to 4.95-fold higher and 9.23 to 24.6-fold higher after the third injection compared with baseline in those who were dengue seropositive and dengue seronegative, respectively. Pain was the most commonly reported solicited injection site reaction after the first injection in both the CYD-TDV (6.3%) and placebo groups (4.9%), but occurred less frequently after subsequent injections. No serious adverse events were vaccine-related, no immediate unsolicited adverse events, and no virologically-confirmed cases of dengue, were reported during the study. The immunogenicity and safety of CYD-TDV was satisfactory in both dengue seropositive and seronegative Indian adults.
| S-EPMC5049724 | biostudies-literature
Project description:INO-4800 represents a DNA-based vaccine encoding the spike protein of SARS-CoV-2. This phase 2 trial evaluated the immunogenicity and safety of INO-4800 as a primary vaccination series in adults. We conducted a randomized, observer-blind, placebo-controlled phase 2 trial of intradermal injection of INO-4800 in both healthy adults and elderly individuals. Eligible participants from each age group were enrolled and randomly assigned in a 3:3:2 ratio to receive two doses of INO-4800 (1.0 mg or 2.0 mg) or placebo, followed by electroporation on day 0 and day 28. The primary immunogenicity endpoints focused on determining the geometric mean titers (GMTs) of spike-binding antibodies and live SARS-CoV-2 neutralizing antibody at day 30 after the second dose. The primary endpoint for safety was the occurrence of adverse events within 30 days after vaccination. A total of 781 volunteers were recruited and screened for eligibility, with 320 eligible young adults (≥18 to <60 years old) and 320 elderly (≥60 to ≤85 years old) were randomly assigned to receive the low-dose (1.0 mg, n = 120) or high-dose (2.0 mg, n = 120) INO-4800, or placebo (n = 80). Notably, both dose groups exhibited significant increases in spike-binding antibodies at day 30 after the second dose, with GMTs of 1609.3 (95% CI: 1385.5-1869.3) for the low-dose group and 3016.7 (95% CI: 2577.4-3530.8) for the high-dose group. Additionally, both dose groups induced neutralizing antibodies against live SARS-CoV-2, with GMTs of 4.7 (95% CI: 4.2-5.3) and 6.6 (95% CI: 5.9-7.4) at day 30 after the second dose. The incidence of adverse events within 30 days after vaccination was slightly higher in the high-dose group (115 [47.9%]) than that in the low-dose group (105 [43.8%]) (p = .0060). All adverse reactions were grade 1 or 2, primarily occurring within 14 days after vaccination. No vaccine-related serious adverse events were reported. The COVID-19 DNA vaccine INO-4800 at two doses (1.0 mg or 2.0 mg) showed an acceptable safety profile and modest immunogenicity, with the high-dose slightly more immunogenic than the low-dose.Clinical Trials Registration: www.chictr.org.cn, identifier is ChiCTR2000040146.
| S-EPMC11776483 | biostudies-literature
Project description:Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 μg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 μg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04-99.96; 344 of 345 participants) and 99.13% (94.27-99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.
| S-EPMC10793708 | biostudies-literature
Project description:BackgroundA novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.MethodsThis prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment.ResultsConjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg) and 3.9-fold (370 μg) (mPP).ConclusionThree-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.
| S-EPMC5947135 | biostudies-literature
Project description:High doses of rifampin may help patients with tuberculous meningitis (TBM) to survive. Pharmacokinetic pharmacodynamic evaluations suggested that rifampin doses higher than 13 mg/kg given intravenously or 20 mg/kg given orally (as previously studied) are warranted to maximize treatment response. In a double-blind, randomized, placebo-controlled phase II trial, we assigned 60 adult TBM patients in Bandung, Indonesia, to standard 450 mg, 900 mg, or 1,350 mg (10, 20, and 30 mg/kg) oral rifampin combined with other TB drugs for 30 days. The endpoints included pharmacokinetic measures, adverse events, and survival. A double and triple dose of oral rifampin led to 3- and 5-fold higher geometric mean total exposures in plasma in the critical early days (2 ± 1) of treatment (area under the concentration-time curve from 0 to 24 h [AUC0-24], 53.5 mg · h/liter versus 170.6 mg · h/liter and 293.5 mg · h/liter, respectively; P < 0.001), with proportional increases in cerebrospinal fluid (CSF) concentrations and without an increase in the incidence of grade 3 or 4 adverse events. The 6-month mortality was 7/20 (35%), 9/20 (45%), and 3/20 (15%) in the 10-, 20-, and 30-mg/kg groups, respectively (P = 0.12). A tripling of the standard dose caused a large increase in rifampin exposure in plasma and CSF and was safe. The survival benefit with this dose should now be evaluated in a larger phase III clinical trial. (This study has been registered at ClinicalTrials.gov under identifier NCT02169882.).
| S-EPMC6256787 | biostudies-literature
Project description:Tetrodotoxin (TTX) has emerged as a potentially efficacious agent for chemotherapy-induced neuropathic pain (CINP), a prevalent, debilitating condition often resistant to analgesics. This randomized, double-blind, dose-finding study was undertaken to explore safety and trends in efficacy of four TTX doses and to identify a dose for further study. One hundred and twenty-five patients with taxane- or platinum-related CINP received subcutaneous placebo or TTX (7.5 µg twice daily (BID), 15 µg BID, 30 µg once daily (QD), 30 µg BID) for four consecutive days. Primary outcome measure was average patient-reported Numeric Pain Rating Scale (NPRS) score during Days 21-28 post-treatment. Changes in mean NPRS score were not statistically different between cohorts, due to small trial size and influence of a few robust placebo responders. Cumulative responder analysis showed significant difference from placebo with 30 µg BID cohort using the maximum response at any timepoint (p = 0.072), 5-day (p = 0.059), 10-day (p = 0.027), and 20-day (p = 0.071) rolling averages. In secondary quality of life (QOL) outcomes, 30 µg BID cohort also differed significantly from placebo in a number of SF-36 and CIPN20 subscales. Most adverse events (AE) were mild or moderate with oral paresthesia (29.6%) and oral hypoesthesia (24.8%) as most common.
| S-EPMC8064362 | biostudies-literature
Project description: Not available
| S-EPMC9760110 | biostudies-literature
Project description:BackgroundWest Nile virus (WNV) is the most common mosquito-borne infection in the United States. HydroVax-001 WNV is a hydrogen peroxide inactivated, whole virion (WNV-Kunjin strain) vaccine adjuvanted with aluminum hydroxide.MethodsWe performed a phase 1, randomized, placebo-controlled, double-blind (within dosing group), dose escalation clinical trial of the HydroVax-001 WNV vaccine administered via intramuscular injection. This trial evaluated 1 mcg and 4 mcg dosages of HydroVax-001 WNV vaccine given intramuscularly on day 1 and day 29 in healthy adults. The two dosing groups of HydroVax-001 were enrolled sequentially and each group consisted of 20 individuals who received HydroVax-001 and 5 who received placebo. Safety was assessed at all study days (days 1, 2, 4 and 15 post dose 1, and days 1, 2, 4, 15, 29, 57, 180 and 365 post dose 2), and reactogenicity was assessed for 14 days after administration of each dose. Immunogenicity was measured by WNV-specific plaque reduction neutralization tests (PRNT50) in the presence or absence of added complement or by WNV-specific enzyme-linked immunosorbent assays (ELISA).ResultsHydroVax-001 was safe and well-tolerated as there were no serious adverse events or concerning safety signals. At the 1 mcg dose, HydroVax-001 was not immunogenic by PRNT50 but elicited up to 41% seroconversion by WNV-specific ELISA in the per-protocol population (PP) after the second dose. At the 4 mcg dose, HydroVax-001 elicited neutralizing antibody responses in 31% of the PP following the second dose. In the presence of added complement, PRNT50 seroconversion rates increased to 50%, and 75% seroconversion was observed by WNV-specific ELISA.ConclusionsThe HydroVax-001 WNV vaccine was found to be modestly immunogenic and well-tolerated at all dose levels.
| S-EPMC6640644 | biostudies-literature
Project description:BackgroundA/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important.MethodsIn this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data.ResultsSingle MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3-<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate.ConclusionsA single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations.Clinical trials registrationClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945).
| S-EPMC4542591 | biostudies-literature
Project description:BackgroundVaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate.MethodsIn this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo. In Part 1, younger (18-54 years) and, in Part 2, older (≥55 years) adults seronegative for SARS-CoV-2 nucleocapsid received one of four V590 dose levels (5.00 × 105; 2.40 × 106; 1.15 × 107; or 5.55 × 107 plaque-forming units [pfu]) or placebo. In Part 3, a single V590 dose level (5.55 × 10⁷ pfu) or placebo was administered to younger SARS-CoV-2 seropositive adults. Primary endpoints included adverse events (AEs) and for Parts 1 and 2 anti-SARS-CoV-2 serum neutralising antibody responses measured by 50% plaque reduction neutralisation (PRNT50) assay at Day 28. Registration NCT04569786 [P001-02].Findings232 participants were randomised and 219 completed the study. In seronegative participants, anti-SARS-CoV-2 spike-specific antibody responses to V590 were low and comparable to placebo across the lower dose levels. At the highest dose level (5.55 × 107 pfu), anti-SARS-CoV-2 spike-specific PRNT50 was 2.3-fold higher than placebo. The most frequently reported AEs were injection-site pain (38.4%), headache (15.1%) and fatigue (13.4%).InterpretationV590 was generally well-tolerated. However, Day 28 anti-SARS-Cov-2 spike-specific antibody responses in seronegative participants following a single intramuscular administration of V590 were not sufficient to warrant continued development.FundingThe study was funded by Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
| S-EPMC9259069 | biostudies-literature