UMEM Research Studies

Background:  

Community-Acquired Pneumonia (CAP) is an infection of the lung parenchyma that develops in people outside of a healthcare facility and is associated with significant morbidity and mortality. Adults ≥ 65 years of age have especially high morbidity and mortality related to CAP and are hospitalized more frequently with the disease compared to younger populations. In 2011, 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) was licensed for use for active immunization for the prevention of pneumonia and invasive diseases caused by 13 S. pneumoniae serotypes. 13vPnC is effective and has substantial public-health benefit; however, non-13vPnC serotypes cause a significant amount of adult pneumococcal disease. Therefore, 20-Valent Pneumococcal Conjugate Vaccine (20vPnC) was developed to further expand protection against the global burden of vaccine-preventable pneumococcal disease beyond that of 13vPnC. Phase 1, 2, and 3 studies assessing the safety and immunogenicity of 20vPnC have demonstrated that the vaccine induces immune response to the 20 vaccine serotypes, has a safety profile consistent with 13vPnC, and is anticipated to expand protection against pneumococcal disease in adults. Thus, this is a Phase 4, multicenter, observational study using a test-negative design, to assess the effectiveness of 20vPnC among patients hospitalized with radiologically-confirmed community-acquired pneumonia.  

Primary Objective:  

To determine the effectiveness of 20vPnC against all (invasive + non-invasive) radiologically-confirmed community-acquired pneumonia (RAD+CAP) caused by the 7 additional serotypes contained in 20vPNC beyond licensed 13vPNC among adults ≥ 65 years of age.  

Secondary Objective:  

To determine the effectiveness of 20vPnC against non-invasive RAD+CAP due to the 7 additional serotypes in 20vPnC beyond 13vPnC (i.e., restricted to participants where S. pneumoniae is not isolated from a normally sterile site).  

To determine the effectiveness of 20vPnC against all RAD+CAP due to any 20vPnC serotype.  

Key Inclusion Criteria:  

Key Exclusion Criteria:  

Study Treatments:  

The planned enrollment is 12,500 adult participants admitted at approximately 15 clinical sites. All participants will have a non-invasive, protocol-specified urine specimen collected for pneumococcal detection and vaccine serotype determination. All other clinical and medical data collected will be done through direct participant interview and review of medical records. Participants are expected to participate for up to 2 days if the interview and urine collection cannot occur on Day 1. Additional data collection including vital status at Day 30 will be performed.  

Primary Endpoint:  

Secondary: 

Study Design:  

This Phase III study is designed as a randomized, double-blind, two-armed, placebo-controlled study. It will be conducted at two centers in the United States. The primary aim is to compare the efficacy of conestat alfa with a placebo in the treatment of ACE-I-induced AE based on the TMDC endpoint, assess its safety and tolerability, as well as compare its efficacy compared to the placebo based on the TOSR endpoint. Moreover, the proportion of patients in each arm who are hospitalized, admitted to the ICU, or who require an airway intervention will be compared.   

A total of 24 patients, 18 years of age or older, who present with suspected ACE-I-induced AE will be eligible to be enrolled in this study. Patients must meet all the inclusion and exclusion criteria. They must also be experiencing an attack that is at least moderate in severity with one of the four primary efficacy airway symptoms (e.g., score of ≥ 2 for any of the following airway compromising symptoms: difficulty breathing, difficulty swallowing, voice changes, and tongue swelling. The duration of the attack must be less than 24 hours at the time of enrollment. All enrolled patients will be treated with the usual ED SOC in addition to study drug.  

Patients who meet all the eligibility criteria will be enrolled and randomized at a 1:1 ratio to receive a single IV injection either 50IU/kg dose for weights <84 kg and up to a maximum dose of 4200 IU for weights ≥84kg of IV conestat alfa or placebo. IDS Pharmacy will prepare the study drug for administration. The study drug will be administered via IV bag after reconstitution over 5 minutes. A second dose of open label conestat alfa can be administered 2 hours after the first dose as a rescue medication if the subject has not experienced symptom relief (based upon TOSR evaluation). ACE-I treatment will be discontinued for all subjects and substituted, if necessary, with an alternative blood pressure medication at the discretion of the treating clinician. 

Usual care for the management of AE may be provided at any time by the clinical care team in the ED. The use of these and other medications, such as inhaled beta-agonists, will be recorded as concomitant medications and will be identified as therapies administered for the treatment of symptoms of ACE-I-induced AE.  

Patients will be required to stay in the ED or the hospital for a minimum of 8 hours for monitoring and safety assessments. Patients can be discharged after 8 hours if they have reached the TMDC endpoint  

and are deemed clinically stable by the clinician providing routine care. Otherwise, they will remain in the ED or hospital until the endpoint is reached. Airway symptom assessment will be performed every 2 hours after the 8-hour mark until the total time equals 24 hours. Airway symptom assessment will not be performed past 24 hours. 

Clinicaltrials.gov ID: NCT06679426