Placebo response

INTRODUCTION: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine...

In the KEEPsAKE 1 (NCT03675308) and KEEPsAKE 2 (NCT03671148) phase 3 trials, risankizumab demonstrated greater efficacy compared with placebo in patients with active psoriatic arthritis (PsA). This post hoc integrated analysis evaluated achieving the following efficacy outcomes at weeks 24 and 52 by baseline demographics and clinical characteristics: ≥20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70), ≥90% improvement in Psoriasis Area and Severity Index, minimal disease activity status, Low Disease Activity status (Disease Activity in Psoriatic Arthritis), and minimal clinically important difference in pain...

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%-94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD...

BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy. METHODS: We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA...

BACKGROUND: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. METHODS: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0...

Adenovirus vaccines, particularly the COVID-19 Ad5-nCoV adenovirus vaccine, have emerged as promising tools in the fight against infectious diseases. In this study, we investigated the structure of the T cell response to the Spike protein of the SARS-CoV-2 virus used in the COVID-19 Ad5-nCoV adenoviral vaccine in a phase 3 clinical trial (NCT04540419). In 69 participants, we collected peripheral blood samples at four time points after vaccination or placebo injection. Sequencing of T cell receptor repertoires from Spike-stimulated T cell cultures at day 14 from 17 vaccinated revealed a more diverse CD4+ T cell repertoire compared to CD8+ ...

Abrocitinib is a highly selective Janus kinase 1 (JAK1) inhibitor that can block a multitude of inflammatory signaling pathways that underlie atopic dermatitis (AD). In addition, abrocitinib inhibits JAK1 signaling in sensory neurons to alleviate acute and chronic pruritus during AD. However, substantial variations in efficacy and safety risks remain due to variations in doses applied in clinical use. Therefore for the present study, differences in the efficacy and tolerability of 100 and 200 mg abrocitinib for treating pruritus and eczema symptoms in patients with moderate-to-severe AD were evaluated compared with placebo...

Ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family inhibitor, was evaluated in patients with ulcerative colitis (UC) in a phase 2b trial. Model-informed drug development strategies were applied to bridge observations from phase 2b to predictions for a proposed phase 3 study design to assess the probability of achieving the target efficacy outcome. A longitudinal exposure-response model of the time course of the 4 Mayo subscores (rectal bleeding, stool frequency, physician's global assessment, and endoscopic subscore) in patients with UC receiving placebo or ritlecitinib was developed using population modeling approaches and an item response theory framework...

Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partial/ non-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries)...

BACKGROUND: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 ( TP53 ) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27...

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae , has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis , may provide cross-protection against the closely related bacterium N...

STUDY OBJECTIVES: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. METHODS: A total of 209 adult patients with a baseline International Restless Legs Syndrome (IRLS) score ≥15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study Days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose...

IMPORTANCE: Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data. OBJECTIVE: To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors...

INTRODUCTION: The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2-5 studies in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from US patients enrolled in the phase 3 FUTURE 2-5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo...

BACKGROUND: Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS)...

BACKGROUND: The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions...

OBJECTIVE: To report 5-year efficacy and safety of upadacitinib in rheumatoid arthritis (RA) from the phase 3 long-term extension (LTE) of SELECT-NEXT. METHODS: Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to upadacitinib 15 mg, upadacitinib 30 mg once daily (UPA15/30), or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA15 or UPA30 in the LTE; upadacitinib-randomized patients continued their original dose...

OBJECTIVES: To observe the effects of moxibustion on intestinal barrier function and Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway in obese rats and explore the mechanism of moxibustion in the intervention of obesity. METHODS: Fifty-five Wistar rats of SPF grade were randomly divided into a normal group (10 rats) and a modeling group (45 rats). In the modeling group, the obesity model was established by feeding high-fat diet...

BACKGROUND: Plane warts when multiple and recurrent present a therapeutic challenge acting as a source of reinfection causing frustration and affecting patient's quality of life. For lesions of large numbers in cosmetically significant sites, topical treatment is preferred to avoid potential sequelae. OBJECTIVES: To evaluate and compare the efficacy and tolerability of tazarotene 0.1% gel versus imiquimod 5% cream for the treatment of plane warts. METHODS: In a parallel three-arm randomized controlled trial, 60 patients were randomized into imiquimod, tazarotene or placebo groups...

BACKGROUND: Psoriasis is a chronic skin condition, for which the approval of several biologics has made a dramatic impact. Despite their initial treatment effectiveness, the challenge lies in understanding the long-term responses, as they may diminish over time. Limitations of the drug survival analysis warrant the application of additional outcomes to fully capture the performance of a biologic. We aimed to provide a broader perspective on the global landscape of biologic agents' persistence in positive clinical response by comparing innovative therapies over a 5-year period through a systematic review and network meta-analysis (NMA)...