Gwaelod-y-garth, Cardiff, United Kingdom

A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough

The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained chronic cough) at 12 weeks.

A Study of ABI-2280 Vaginal Insert (Previously Referred to as ABI-2280 Vaginal Tablet) in Participants With Cervical Intraepithelial Neoplasia

Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL

This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure. The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.

Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment Trial

The trial will be a single blinded randomised controlled, pragmatic, medical device trial evaluating a Whole Genome Sequencing (WGS) Drug Sensitivity Testing (DST) strategy to guide individualised treatment of rifampicin resistant tuberculosis (RR-TB) patients. A total of 248 patients diagnosed with RR-TB in the South African Free State province will by randomised to one of two trial arms. 124 patients will be assigned to the intervention arm, consisting of a WGS DST strategy for diagnosing drug resistance profile and an algorithm-determined individualised RR-TB treatment recommendation. 124 patients will be assigned to the control arm where the diagnosis of Mtb drug resistance and individualisation of RR-TB treatment will happen according to the Standard of Care (SOC) procedures.

Sisonke 2 - A COVID-19 Vaccine Boost Open Label Study.

Purpose To evaluate the effectiveness and safety of the single dose Ad26.COV2.S (Jansen) COVID-19 vaccine plus a homologous boost with Ad26.COV2.S (Janssen) COVID-19 vaccine among Sisonke participants as compared to unboosted Sisonke participants In addition the investigators will continue to evaluate VE of the Sisonke Boost compared to: i) Vaccinated populations pre boosts ii) Unvaccinated populations in South Africa. Study design Open-label, single-arm phase 3B vaccine implementation study Rationale South Africa is severely affected by the global COVID-19 epidemic, and following the initial prime vaccination among HCWs in the first 4 months of 2021. New data has demonstrated the safety and effectiveness of a booster dose given two months or more after the initial Ad26.COV2.S. This provides the rationale and feasibility for the evaluation of a homologous booster vaccine dose to the cohort of vaccinated Sisonke participants to inform the larger vaccine rollout. Study participants Sisonke participants age 18 and over working in the South African public and private health care sector (approx N=500 000) who were enrolled in Sisonke and have not subsequently had a further booster vaccine dose. Study sites Department of Health Vaccine Administration Sites across South Africa supported by the Sisonke (Together) (VAC31518COV3012) Trial Research Site Investigators and Study Staff Study duration Participants will receive a homologous Ad26.COV2.S (Janssen) booster dose of vaccine at least 6 months post the prime vaccination. The investigators will monitor outcomes utilising the DATCOV surveillance system and NHLS/NICD SARS COV-2 testing databases for up to 2 years post initial vaccination. Study products Ad26.COV2.S by Janssen administered as a single dose followed by a single booster injection. Primary objectives • To assess the effectiveness of Ad26.COV2.S vaccine as a homologous boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared with the unboosted Sisonke populations. Secondary objectives To assess the effectiveness of Ad26.COV2.S vaccine as a homologous boost on severe COVID, hospitalizations and deaths in Sisonke participants as compared vaccinated and unvaccinated populations of essential workers in South Africa. - To estimate the incidence of symptomatic SARS CoV-2 infections in Sisonke participants following a boost compared with the unboosted Sisonke populations and general vaccinated and unvaccinated population in South Africa - To estimate booster dose uptake among Sisonke participants in South Africa - To monitor the genetic diversity of breakthrough SARS CoV-2 infections. - To monitor safety in the case of homologous boosts in Sisonke participants.

Therapeutic Use of Convalescent Plasma in the Treatment of Patients With Moderate to Severe COVID-19

Full Title: A prospective, randomized, placebo-controlled, double-blinded, phase III clinical trial of the therapeutic use of convalescent plasma in the treatment of patients with moderate to severe COVID-19. Short Title: PROTECT-Patient study Aim: Assess the safety and efficacy of COVID-19 convalescent plasma (CCP) as a therapeutic treatment for hospitalised patients with moderate to severe COVID-19 Study Design: Randomised, double-blinded, placebo-controlled, phase III clinical trial Intervention: Randomised 1:1 to either CCP plus standard of care (SOC) or to SOC plus placebo (200 mL normal saline) Active Agent: A single unit of approximately 200-250 mL of CCP that contains anti-SARS-CoV-2 collected by plasmapheresis from a volunteer who recovered from COVID19 with SOC as determined by local practice and guidelines. Placebo: A single unit of 200 mL normal saline with SOC as determined by local practice and guidelines Sample Size: 600 Study Population: Consenting adult inpatients with moderate to severe COVID-19, not requiring invasive ventilation, who are admitted to a participating public or private sector hospital and who are not enrolled in another COVID-19 treatment trial. Settings: Participating public and private sector hospitals in South Africa

Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Adolescent ORION-16 or ORION-13 Studies

This is an open-label, single arm, multicenter study designed to evaluate long-term safety and tolerability of inclisiran. In addition, the study will provide participants the opportunity to have continued access to treatment with inclisiran.

Post-Trial Tuberculosis Case Finding: A Substudy of CoVPN 3008

This observational substudy will involve participants from the CoVPN 3008 trial, regardless of their HIV status, to study tuberculosis (TB). At the start, all participants will be screened for TB, even if they have no symptoms. They will receive chest x-rays and provide sputum samples for TB testing using Xpert Ultra, smear microscopy, and culture. The study has two main groups. Group 1 includes participants with confirmed TB, and Group 2 includes participants without TB who will act as controls. Participants with confirmed TB will start treatment and have a first follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. A second follow-up visit will take place at week 26 to evaluate their treatment progress, clinical outcomes, and TB status, ensuring they receive the necessary care. Participants without TB will have a single follow-up visit on Day 4 to reassess TB symptoms and collect blood samples. The study aims to identify potential biomarkers of TB by analyzing blood samples from both cases and controls, focusing on gene expression linked to TB, including hidden (subclinical) TB.

An Extension and Crossover Vaccination Study on the Immune Response and Safety of a Vaccine Against Respiratory Syncytial Virus Given to Adults 60 Years of Age and Above Who Participated in RSV OA=ADJ-006 Study

Study to Demonstrate Pharmacokinetic and Pharmacodynamic Similarity Between NKF-INS Glargine (G), United States (US)-Lantus®, and European Union (EU)-Lantus®

A single center, single-dose, double-blind, randomized, three-period, three-treatment, six-sequence, crossover study to demonstrate pharmacokinetic and pharmacodynamic similarity between NKF-INS(G), US-Lantus®, and EU-Lantus® using the euglycemic clamp technique in healthy male adult volunteers