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

NCT ID: NCT06766825

Last Updated: 2025-02-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-07
• Study Completion Date: 2026-06-01

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.

Detailed Description

Plitidepsin, a marine-derived cyclic depsipeptide that inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A, could be a suitable candidate treatment for "Long COVID" because of a triple mechanism of action; a) it has demonstrated potent anti-SARS-CoV-2 in vitro activity, (b) it has a systemic anti-inflammatory effect, detailed in the text below, and (c) has an anti-herpes antiviral effect, which could provide additional therapeutic benefits to prevent herpesvirus reactivation seen in Long-COVID.

An interim analysis will be conducted upon reaching 30% and 50% of recruitment (patients treated with at least one dose and 28 days (+/- 2 days) of FUP)). The first interim analysis will focus exclusively on safety assessment, based on adverse events reported to date. The second interim analysis (50%) will evaluate safety and futility. A blinded safety report will be prepared, summarizing adverse events, and submitted to the Data Safety Monitoring Board (DSMB) for review and to determine whether to continue, modify, or terminate the study

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A. Plitidepsin Arm

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.

Group Type: EXPERIMENTAL

Plitidepsin 1.5 mg/day

Intervention Type: 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.

B. Placebo/Plitidepsin

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).

Group Type: EXPERIMENTAL

Placebo and Plitidepsin 1.5mg/day

Intervention Type: 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.

C. Placebo Arm

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Plitidepsin 1.5 mg/day

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Placebo and Plitidepsin 1.5mg/day

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.

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

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 (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 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).

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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

IrsiCaixa

OTHER

Sponsor Role: collaborator

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Lourdes Mateu Pruñonosa, phD, MD

Role: CONTACT

lmateu@lluita.org

+34 93 465 78 97

Cora Loste, phD, MD

Role: CONTACT

closte@lluita.org

+34 93 465 78 97

Facility Contacts

Lourdes Mateu Pruñonosa, phD, MD

Role: primary

assaigs@scienhub.org

(+34) 934657897

Cora Loste Andreu, phD, MD

Role: backup

closte@lluita.org

(+34) 934657897

Other Identifiers

2024-516378-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

THALASSA 2.0

Identifier Type: -

Identifier Source: org_study_id