PLITIDEPSIN for Post-COVID-19 Condition (PCC) | Post-COVID-19 syndrome

Inclusion criteria

• {"criterion_text":"- Male or female individuals 18 years old or older.\n- Evidence of SARS-CoV-2 infection at least 90 days prior to study recruitment, defined by either (a) nasopharyngeal SARS-CoV-2 nucleic acid test [polymerase chain reaction (PCR) or transcription mediated amplification (TMA)], (b) validated Nasopharyngeal Lateral Flow Assay rapid antigen test (RAT), or (c) or positive serology against SARS-CoV-2 N protein regardless vaccination status.\n- 3 or more symptoms of PCC affecting at least two organs, after 90 days from the onset of SARS-CoV2 infection and that last for at least 2 months and cannot explained by an alternative diagnosis. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.\n- Unable to perform all usual duties/activities, defined as grades 3 or 4 in PCFS\n- Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.\n- Having understood the information provided and capable of providing informed consent."}

Exclusion criteria

• {"criterion_text":"- Last SARS-CoV-2 vaccine dose during the previous 30 days\n- Females of childbearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using highly effective contraceptive methods, while on study treatment and for 6 months after last dose of plitidepsin. Fertile males with partners of childbearing potential must use condom during treatment and for 6 months after last dose of plitidepsin. Refer to Protocol's Annex 2 for contraception requirements.\n- Unable to consent and/or comply with study requirements, in the opinion of the investigator\n- Currently participating or participated in a clinical trial within the prior 30 days, or a planned participation in any other clinical trial within the next 138 days.\n- Patients with active uncontrolled infections.\n- Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.\n- Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Protocol's Annex 1) throughout plitidepsin treatment period and until 24-h washout period.\n- Pacients receiving chronic glucocorticoid therapy (. high-dose corticosteroids [ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)\n- Any of the following cardiac conditions or risk factors: •\tCardiac infarction or cardiac surgery episode within the last six months; •\tHistory of known congenital QT prolongation; •\tKnown structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) <50%; •\tCurrent clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).\n- Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or contraindication to receive systemic glucocorticoids, antihistamine H1/H2 receptor agents, or antiserotonine 5HT3 receptors drugs.\n- Mast cell activation syndrome.\n- Females who are pregnant (negative serum or urine pregnancy test required for all females of childbearing potential at screening) or breast-feeding."}

Primary endpoints

• {"endpoint_text":"- Difference between groups on the PROMIS-29® health scale measured by T- Score on day 90 (±5) of the follow-up period* (after the intervention period).","definition_or_measurement_approach":"Measured using the PROMIS-29® health scale reported as T-Score on Day 90 (±5) of follow-up (after intervention period)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of adverse events (AE, coded by MedDRA) comparing between groups at day 90 (±5) of the follow-up period, considering: 1) All AEs. 2) AEs grade 3 and 4 leading to discontinuation from the study. 3) AEs of special interest (AESI): cardiac, liver, acute-infusional reactions.","definition_or_measurement_approach":"AE incidence coded by MedDRA and compared between groups at Day 90 (±5); includes overall AEs, grade 3-4 leading to discontinuation, and AESIs (cardiac, liver, acute-infusional reactions)."}
• {"endpoint_text":"- Percentage of TEAEs detected on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Treatment-Emergent Adverse Events (TEAEs) measured as percentage at Days 10 (±2), 30 (±2) and 90 (±5)."}
• {"endpoint_text":"- Percentage of TEAEs detected on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Duplicate entry in source; measurement as above."}
• {"endpoint_text":"- Difference between groups on the PROMIS-29® health scale measured by T-Score on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"PROMIS-29® T-Score differences assessed at Days 10 (±2), 30 (±2) and 90 (±5)."}
• {"endpoint_text":"- Difference between groups in functional capacity on the PCFS scale on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Functional capacity measured by the Post-COVID-19 Functional State (PCFS) scale at Days 10 (±2), 30 (±2), and 90 (±5)."}
• {"endpoint_text":"- Proportion of subjects with ≥10 points reduction in the Can Ruti Questionnaire scale on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Proportion of subjects achieving ≥10 point reduction in Can Ruti Questionnaire at Days 10, 30 and 90 (with specified windows)."}
• {"endpoint_text":"- Difference between groups according to the EuroQoL-5D questionnaire on day 10 (±2), day 30 (±2), and day 90 (±5) a of the follow-up period.","definition_or_measurement_approach":"Quality of life measured by EuroQoL-5D at Days 10, 30 and 90 (± windows)."}
• {"endpoint_text":"- Change from baseline in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, measured using the following questionnaires: Neu Screen (psychomotor speed and executive function); PHQ-9 (depressive symptoms); GAD-7 (anxiety symptoms); PSQI (Sleep quality); and WHODAS 2.0 (disability).","definition_or_measurement_approach":"Neuropsychological symptom changes measured by Neu Screen, PHQ-9, GAD-7, PSQI and WHODAS 2.0 at Days 10, 30 and 90 (± windows)."}
• {"endpoint_text":"- Change from baseline in physical activity to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, assessed using the International Physical Activity Questionnaire (IPAQ).","definition_or_measurement_approach":"Physical activity assessed by IPAQ at Days 10, 30 and 90 (± windows)."}
• {"endpoint_text":"- Change from baseline in physical activity to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, evaluated using the Fatigue Severity Scale (FSS) and the Five Times Sit-to-Stand Test (5xSTS).","definition_or_measurement_approach":"Fatigue and physical performance measured by FSS and 5xSTS at Days 10, 30 and 90."}
• {"endpoint_text":"- Change from baseline in inflammation markers on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Inflammatory biomarkers measured and compared at Days 10, 30 and 90."}
• {"endpoint_text":"- Change from baseline in immunological assessments (including autoimmunity) to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Immunological assessments including autoimmunity markers measured at Days 10, 30 and 90."}
• {"endpoint_text":"- Change from baseline in viral components in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Viral components in plasma measured at Days 10, 30 and 90."}
• {"endpoint_text":"- Change from baseline in thromboinflammatory and complement activation components in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Thromboinflammatory and complement activation markers measured at Days 10, 30 and 90."}
• {"endpoint_text":"- Change from baseline in hormonal component alterations in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Hormonal component alterations measured at Days 10, 30 and 90."}
• {"endpoint_text":"- Exploratory Endpoint for future investigations: Change from baseline in intestinal microbiota in stool samples at Day 10 (±2), Day 30 (±2), and Day 90 (±5) of the follow-up period.","definition_or_measurement_approach":"Exploratory analysis of intestinal microbiota in stool samples at Days 10, 30 and 90."}

Spain

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

05-12-2024

Processing Time Days

35

Number Of Sites

1

Number Of Participants

90

Primary sponsor

Full Name

Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"PharmaMar and Sponsor Resources","duties_or_roles":"Source of monetary support","organisation_type":""}