Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults with Post-COVID-19 Condition (PCC)

NCT06766825 | Recruiting Phase 2 DMC

• 2 other identifiers: THALASSA 2.02024-516378-31-00
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to prove that plitidepsin could be an efficacious, safe, and well-tolerated therapy for PCC. To this end, we will perform a randomized, double-blind study comparing the clinical and laboratory benefits of plitidepsin vs. placebo in 90 subjects with moderate to severe functional disability. The study consists of an intervention period and a follow-up period, with a total of 135 +/-3 days approximately between both periods. During the intervention period, four treatment cycles will be administered, scheduled every 15 days (every 2 weeks), with intravenous (IV) infusion over three consecutive days. After completing the intervention period, a 90-day (+/-5) follow-up period will be conducted. Subjects in arm A will receive the plitidepsin 1.5 mg/day 1h-IV during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31 and Days 43 to 45. Subjects in arm B will receive 1h-IV placebo 1 vial /day during the first two treatment periods and will receive the plitidepsin 1.5 mg/day 1h-IV during the last two treatment periods. Subjects in arm C will receive 1h-IV placebo 1 vial/day during the four treatment periods.

Conditions

Post COVID-19 Condition; Long COVID Syndrome; Persistent COVID-19; Persistent COVID Condition; Long COVID

Keywords

SARS-CoV-2; COVID-19; Long COVID19; Plitidepsin

Outcome Measures

Primary Outcomes (1)

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

  Difference between groups on the patient-reported outcomes measurement information system (PROMIS-29®) score health scale measured by T-Score; Each domain is scored on a 5-point scale, (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do), in case of the pain domain is on a 10-point scale; from no pain to the worse pain. on day 90 (±5) of the follow-up period\* (after the intervention).

  On day 90 of follow-up period

Secondary Outcomes (28)

• To compare the safety/tolerability of Plitidepsin Vs placebo in terms of adverse events in patients with PCC.

  On day 90 of follow-up period

• To compare the incidence of Treatment-Emergent Adverse Events (TEAEs) between groups.

  On day 10, day 30 and day 90 of follow-up period

• To compare changes in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).

  On day 10, day 30 and day 90 of follow-up period

• To compare functional capacity changes in patients from each group using the post-COVID-19 Functional State (PCFS) scale.

  On day 10, day 30 and day 90 of follow-up period

• To compare symptomatic changes in patients from each group using the Can Ruti Questionnaire.

  On day 10, day 30 and day 90 of follow-up period

Study Arms (3)

A. Plitidepsin Arm

EXPERIMENTAL

Subjects in arm A will receive the plitidepsin 1.5 mg/day 1h-IV during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31 and Days 43 to 45.

Drug: Plitidepsin 1.5 mg/day

B. Placebo/Plitidepsin

EXPERIMENTAL

Subjects in arm B will receive 1h-IV placebo 1 vial /day during the first two treatment periods (Days 1 to 3 and Days 15 to 17) and plitidepsin 1.5 mg/day 1h-IV during the last two treatment periods (Days 29 to 31 and Days 43 to 45).

Drug: Placebo and Plitidepsin 1.5mg/day

C. Placebo Arm

PLACEBO COMPARATOR

Subjects in arm C will receive 1h-IV placebo 1 vial/day during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31, and Days 43 to 45.

Drug: Placebo

Interventions

Plitidepsin 1.5 mg/day DRUG

Receive 1.5 mg/day of plitidepsin intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.

A. Plitidepsin Arm

Placebo DRUG

Receive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.

C. Placebo Arm

Placebo and Plitidepsin 1.5mg/day DRUG

Receive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during two treatment periods and receive plitidepsin 1.5mg/day during the last two treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.

B. Placebo/Plitidepsin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Last SARS-CoV-2 vaccine dose during the previous 30 days.
• Patients with active uncontrolled infections.
• Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.
• Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Annex 1) throughout plitidepsin treatment period and until 24-h washout period.
• Pacients receiving chronic glucocorticoid therapy (high-dose corticosteroids \[ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)
• Any of the following cardiac conditions or risk factors:
• Cardiac infarction or cardiac surgery episode within the last six months 14
• 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).
• 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.
• Mast cell activation syndrome.
• Females who are pregnant (negative serum or urine pregnancy test required for all females of childbearing potential at screening) or breast-feeding.
• 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 Annex 2 for contraception requirements.
• Unable to consent and/or comply with study requirements, in the opinion of the investigator.

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• PharmaMar: collaborator
• IrsiCaixa: collaborator

Study Sites (1)

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

plitidepsin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Lourdes Mateu Pruñonosa, phD, MD

CONTACT

+34 93 465 78 97; lmateu@lluita.org

Cora Loste, phD, MD

CONTACT

+34 93 465 78 97; closte@lluita.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking of investigational products will ensure that both the investigator and the participant are blinded to the product administered. The pharmacist service will be responsible for masking the study treatments. Both treatments (Plitidepsin and placebo) have the same route of administration. All the participants (from all arms) will receive the pre-medication required for the plitidepsin treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized (1:1:1), placebo-controlled, double-blind clinical trial

Study Record Dates

• First Submitted: December 31, 2024
• First Posted: January 9, 2025
• Study Start: February 7, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)