NEREIDA

• Research type

  Research Study

• Full title

  A Multicentre, Open label, Randomised, Controlled, Basket, Pragmatic, Phase II, Clinical and Translational Study to Determine the Efficacy and Safety of Plitidepsin versus Control in Immunocompromised Adult Patients with Symptomatic COVID-19 requiring Hospital Care (NEREIDA)

• IRAS ID

  1006650

• Contact name

  Luis Mora Capitan

• Contact email

  regulatory@pharmamar.com

• Sponsor organisation

  Pharma Mar, S.A.

• Eudract number

  2022-002489-34

• Clinicaltrials.gov Identifier

  NCT05705167

• Research summary

  This study will test the Efficacy and Safety of Plitidepsin versus Control in Immunocompromised Adult Patients with Symptomatic COVID-19 requiring Hospital Care. Immunocompromised patients are at increased risk for severe and fatal COVID 2019 outcomes. Of additional concern is the widespread use of immunosuppressive medications to treat COVID-19. The RECOVERY trial, which showed a significant reduction in mortality among patients with COVID-19 who received dexamethasone, resulted in a paradigm shift in the medical management of COVID-19, whereby immunomodulation and not antiviral therapy has become an accepted clinical practice standard. Given that immunosuppressed patients are at risk for protracted SARS-CoV-2 infection, concerns have been raised about whether immunosuppressive therapies may promote chronic infection and worse outcomes, including selection and transmission of new SARS-CoV-2 variants. Thus, studies among immunocompromised hosts should be focused on identifying direct acting antivirals that markedly reduce SARS-CoV-2 replication. In preclinical studies, plitidepsin showed strong antiviral activity in in vitro models of SARS-CoV-2 infection, also showing a better therapeutic index than other drugs used in the treatment of SARS-CoV-2, including remdesivir.

  The study will include a Screening period, a Treatment period and a Follow-up period lasting, in total approximately 60 days for each participant. All participants will receive the best available supportive care as per applicable local and national COVID-19 treatment guidelines. Participants assigned to the experimental arms will receive, in addition, plitidepsin as a 1-h IV infusion, during days 1 to 3. At the end of the study participants will take part in an end of study visit. Full details of the participant procedures can be found on pages 63 to 75 of the study protocol. The first 30 participants will additionally take part in a PK sub study detailed on page 88 of the study protocol.

  Summary of study results:

  This study was originally planned to enrol approximately 150 participants, divided in 4 different groups of immunocompromised participants. However, enrolment stopped due to low recruitment and early termination of the study has been decided by the sponsor on 23 Feb 2024. The planned primary analysis for the study was not conducted, therefore, only the partial analyses performed for efficacy and safety endpoints are available.

  Overall Conclusions:
  - Treatment with plitidepsin in immunocompromised adult participants with symptomatic COVID-19 have shown reduced disease burden and decrease the requirement of healthcare resources; but these data need to be interpreted with caution due to the relatively small population size.
  - Overall, plitidepsin was well tolerated in immunocompromised adult participants with equivalent safety outcomes in all 4 groups and not different when compared with control arm.
  - Although more deaths were reported in the plitidepsin arm, they were either disease (COVID-19) related or due to pre-existing conditions/ongoing illness.
  - No new safety findings were observed in this participant population.

  This summary shows only the main results from this one study. You can find more information about this study at the websites listed below:

  https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7C1654e406980b4da3f66b08dce3b39c92%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638635607769400104%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=AQqY1nPZYWo4aF2Gvnp9vjBHZqO1ozu%2Bu7TSWxUwsI4%3D&reserved=0 and search NCT05705167
  https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7C1654e406980b4da3f66b08dce3b39c92%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638635607769440611%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=PJQcHllTA2glRt8V2xIh3hC2Rdv2XnLG%2FZNYuYXJQmk%3D&reserved=0 and search 2022-002489-34

• REC name

  London - South East Research Ethics Committee

• REC reference

  23/LO/0103

• Date of REC Opinion

  7 Sep 2023

• REC opinion

  Further Information Favourable Opinion