Phase II proof-of-concept, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of plitidepsin in adults with post-COVID-19 Condition (PCC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

7 Feb 2025 → ongoing

Decision date (initial)

2024-12-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PharmaMar and Sponsor Resources

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Change in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®)

Secondary objectives 15

1. To compare the safety/tolerability of Plitidepsin Vs placebo in terms of adverse events in patients with PCC.
2. To compare the incidence of Treatment-Emergent Adverse Events (TEAEs) between groups.
3. To compare changes in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).
4. To compare functional capacity changes in patients from each group using the post-COVID-19 Functional State (PCFS) scale.
5. To compare symptomatic changes in patients from each group using the Can Ruti Questionnaire.
6. To compare changes in terms of Quality of Life (QoL) for each group.
7. To compare neuropsychological symptomatology in patients with PCC among the three treatment arms.
8. To compare changes in terms of physical activity in patients with PCC among the three arms.
9. To compare changes in terms of fatigue in patients with PCC among the three treatment arms.
10. To compare the evolution of inflammation markers in patients with PCC among the three arms.
11. To compare immune response markers (including autoimmunity) in patients with persistent COVID among the three treatment arms.
12. To compare the presence of viral components in plasma with persistent COVID among the three treatment arms.
13. To compare alterations in thromboinflammatory components and complement activation among the three treatment arms.
14. To compare alterations in hormonal components among the three treatment arms.
15. Exploratory Objective for Future Investigations: To compare changes in intestinal microbiota in patients with persistent COVID among the three treatment arms.

Conditions and MedDRA coding

post-COVID-19 Condition (PCC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Agencia Espanola De Medicamentos Y Productos Sanitarios

Plan to share IPD

No

IPD plan description

Not applicable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female individuals 18 years old or older.
2. 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.
3. 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.
4. Unable to perform all usual duties/activities, defined as grades 3 or 4 in PCFS
5. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
6. Having understood the information provided and capable of providing informed consent.

Exclusion criteria 12

1. Last SARS-CoV-2 vaccine dose during the previous 30 days
2. Patients with active uncontrolled infections.
3. Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.
4. 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.
5. Pacients receiving chronic glucocorticoid therapy (. high-dose corticosteroids [ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)
6. Any of the following cardiac conditions or risk factors: • Cardiac infarction or cardiac surgery episode within the last six months; • History of known congenital QT prolongation; • Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) <50%; • Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).
7. 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.
8. Mast cell activation syndrome.
9. Females who are pregnant (negative serum or urine pregnancy test required for all females of childbearing potential at screening) or breast-feeding.
10. 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.
11. Unable to consent and/or comply with study requirements, in the opinion of the investigator
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 15

1. 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.
2. Percentage of TEAEs detected on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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).
9. 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).
10. Change from baseline in inflammation markers on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
11. Change from baseline in immunological assessments (including autoimmunity) to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
12. Change from baseline in viral components in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
13. 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.
14. 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.
15. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Carretera Canyet S/n

City

Badalona

Postcode

08916

Country

Spain

Scientific contact point

Organisation

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

Contact name

Lourdes Mateu Pruñonosa

Public contact point

Organisation

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

Contact name

Lourdes Mateu Pruñonosa

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications