Efficacy and Safety of Pimodivir Combined with Standard-of-care in Hospitalized and Non-hospitalized High-risk Adolescents and Adults with Influenza A Infection.

BACKGROUND: An unmet need exists for effective antivirals to treat patients hospitalized with influenza. The results of 2 Phase 3 studies evaluating the efficacy and safety of pimodivir in combination with investigator-chosen standard-of-care (SoC) treatment are presented. METHODS: Hospitalized patients (hospital study; NCT03376321) and high-risk outpatients (outpatient study; NCT03381196) with laboratory-confirmed influenza A infection were randomized 1:1 to 600 mg pimodivir twice daily (BID) + SoC, or placebo BID + SoC for 5 days. For most patients SoC included oseltamivir. Primary endpoints were Hospital Recovery Scale (HRS) at Day 6 (hospital study) and median time to resolution (TTR) of influenza-related symptoms (outpatient study). RESULTS: Pimodivir + SoC (oseltamivir) treatment showed no clinical benefit over placebo + SoC on HRS at Day 6 (common odds ratio, 0.943 [95% CI, 0.609-1.462], P = .397; hospital study). A shorter median TTR of 7 symptoms was estimated with pimodivir + SoC versus placebo (92.6 hours [95% CI, 77.6-104.2] versus 105.1 hours [95% CI, 92.7-128.6], P = .0216; outpatient study). CONCLUSION: Pimodivir + SoC showed no additional clinical benefit versus SoC treatment alone in hospitalized patients. Pimodivir + SoC demonstrated shorter TTR of influenza symptoms versus placebo + SoC in high-risk outpatients.

Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose. METHODS: ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing. FINDINGS: Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity. INTERPRETATION: A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed. FUNDING: Janssen Research & Development.

Greater improvement in quality of life outcomes in patients using fixed-combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel: results from the PSO-ABLE study.

BACKGROUND: Health-related quality of life (HRQoL) measures provide patient-centred evaluations of response to treatment. In the 12-week, Phase III PSO-ABLE study, fixed-combination calcipotriol 50 µg/g as hydrate (Cal) plus betamethasone 0.5 mg/g as dipropionate (BD) aerosol foam was significantly more effective for the treatment of psoriasis than Cal/BD gel. OBJECTIVE: To compare HRQoL in mild-severe psoriasis vulgaris patients (involving 2-30% body surface area) over 12 weeks of treatment with Cal/BD foam or gel. METHODS: HRQoL was assessed using: Dermatology Life Quality Index (DLQI), EuroQoL-5D-5L-PSO (EQ-5D), and Psoriasis QoL (PQoL-12) questionnaires (baseline, Weeks 4, 8 and 12); DLQI score of 0/1 (range: 0-30) and weighted EQ-5D utility index score of 1 (range: 0-1) indicates there is no impact on a patient's QoL and perfect health, respectively. Itch, itch-related sleep loss, and work impairment were also assessed. RESULTS: In total, 463 patients were randomized to the study (Cal/BD foam, n = 185; Cal/BD gel, n = 188; foam vehicle, n = 47; gel vehicle, n = 43). Significantly more Cal/BD foam patients achieved DLQI scores of 0/1 at Weeks 4 (45.7% vs 32.4%; p = 0.013) and 12 (60.5% vs 44.1%; p = 0.003) than Cal/BD gel patients. Cal/BD foam significantly improved EQ-5D utility index (0.09 vs 0.03; p<0.001) and PQoL-12 scores (-2.23 vs -2.07; p = 0.029) from baseline to Week 4 versus Cal/BD gel. Itch, itch-related sleep loss, and work impairment improved more with Cal/BD foam than gel. CONCLUSION: Cal/BD foam demonstrated greater HRQoL improvement in patients with psoriasis than Cal/BD gel over 12 weeks of treatment.

Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for Psoriasis Vulgaris: A Randomized, Double-blind, Multicenter, Three-arm, Phase 2 Study.

OBJECTIVE: To evaluate the efficacy of fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD). DESIGN: Patients were randomized (100:101:101) to receive Cal/BD foam, Cal foam, or BD foam once daily for four weeks. SETTING: Twenty-eight United States centers. PARTICIPANTS: 302 patients (≥18 years) with Psoriasis vulgaris (plaque Psoriasis; ≥mild disease severity by physicians global assessment). MEASUREMENTS: Treatment success of the body ("clear"/"almost clear" from baseline moderate/severe disease; "clear" from baseline mild disease). Involved scalp treatment success was an additional endpoint. RESULTS: Most patients (76%) had moderate Psoriasis of the body (66% for scalp). At Week 4, 45 percent of Cal/BD foam patients achieved treatment success, significantly more than Cal foam (14.9%; OR 4.34 [95%CI 2.16,8.72] P<0.001) or BD foam (30.7%; 1.81 [1.00,3.26] P=0.047). Fifty-three percent of Cal/BD foam patients achieved treatment success of the scalp, significantly greater than Cal foam (35.6%; 1.91 [1.09,3.35] P=0.021), but not BD foam (47.5%; 1.24 [0.71,2.16] P=0.45). Mean modified Psoriasis area and severity index (population baseline 7.6) improved in all groups, with statistically significant differences in Week 4 Cal/BD foam score (2.37) versus Cal foam (4.39; mean difference -2.03 [-2.63][-1.43] P<0.001) and BD foam (3.37; -1.19 [-1.80][-0.59] P<0.001). Four (Cal/BD), 10 (Cal), and 8 (BD) adverse drug reactions were reported. CONCLUSION: Cal/BD foam was significantly more effective than Cal foam and BD foam in providing treatment success at Week 4 and effective on involved scalp. TRIAL REGISTRATION: NCT01536938.