Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome

Post-COVID-19 Syndrome Clinical Trial

Official title:

Temelimab as a Disease Modifying Therapy in Patients With Neurological, Neuropsychological, and Psychiatric (=Neuropsychiatric) Symptoms in Post-COVID 19 or Postacute Sequelae of COVID-19 (PASC) Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05497089
• Other study ID #: GNC-501
• Secondary ID: 2022-000618-32
• Status: Completed
• Phase: Phase 2
• Start date: August 29, 2022
• Est. completion date: May 10, 2024

Study information

• Verified date: May 2024
• Source: GeNeuro SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a Phase 2, 24-week, randomized, prospective, double-blind, multicenter study in patients experiencing neuropsychiatric symptoms and functional impairment in the course of PASC. The purpose of the study is to evaluate the efficacy and safety of Temelimab as a treatment for PASC neuropsychiatric symptoms in patients who had severe acute respiratory syndrome coronavirus - type 2 (SARS-CoV-2) infection but did not undergo intensive care treatment during the acute period. Patients meeting eligibility criteria will be randomized to Temelimab or placebo in a 1:1 ratio via interactive voice/web response system to obtain 182 protocol completers. The randomization will be stratified by age (≤65 years versus >65 years).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: May 10, 2024
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• PASC Syndrome in accordance with NICE criteria with neuropsychiatric symptoms still occurring >12 weeks after their first appearance.

• Has had a SARS-CoV-2-positive diagnostic test (using a validated SARS-CoV-2 antigen, reverse transcription polymerase chain reaction [RT-PCR], or other molecular diagnostic assay, and an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva). In case that the local standard of care did not foresee the previously mentioned tests, a confirmed SARS-CoV-2 nucleocapsid or membrane antibody test associated to a medical report documenting the date of COVID-19 clinical diagnostic, will be accepted.

• PROMIS Fatigue SF 7a total raw score =21 with onset of fatigue post coronavirus disease 2019 (COVID-19) infection.

• Patients affected with at least one of the following measures of objective impairment of cognitive function or of quality of life as defined by: i. Token Motor Test =1 z-score below the age/sex-adjusted mean ii. EQ5D-5L: Presence of at least 1 score =3 in any of the 5 variables of EQ5D-5L questionnaire (mobility; self-care; usual activities; pain/discomfort; anxiety/depression) iii. PQD-20 =27

• HERV-W ENV positive as defined by automated capillary western system, specific signal level over background noise (S/N) >1.

Main Exclusion Criteria:

• Intubation and mechanical ventilation in the course of COVID19 or reception of convalescent COVID19 plasma treatment at any time prior to study entry

• Major psychiatric conditions including but not restricted to (e.g. attention deficit/hyperactivity disorder, substance use disorder, schizophrenia documented in patient history or diagnosed using M.I.N.I), at the discretion of the site investigator, these do not refer to patients with typical mild to moderate symptoms of depression and anxiety associated with PASC

• Neurological signs and symptoms including change in level of consciousness, seizures, movement disorders or focal neurological deficits, disorders of the central nervous system with tissue damage or a pre-COVID-19 diagnosis of Chronic Fatigue Syndrome documented in the patient history or diagnosed during the neurological examination

• Current immunosuppressive//immunomodulating medication (e.g., azathioprine, tacrolimus, cyclosporine, methotrexate, hydroxychloroquine, cytotoxic chemotherapy, or neutralizing antibodies against SARS-CoV-2 epitopes) or therapy with HIV protease inhibitors

Related Conditions & MeSH terms

• COVID-19
• Post-COVID-19 Syndrome
• Syndrome

Intervention

Drug:
• Temelimab 54mg/kg
Temelimab 54mg/kg will be given as monthly (every 4 weeks) intravenous (IV) infusion over 24 weeks (6 infusions in total)
• Placebo
Placebo will be given as monthly (every 4 weeks) intravenous (IV) infusion over 24 weeks (6 infusions in total)

Locations

Country	Name	City	State
Italy	Clinica Metabolica dell'Università di Modena e Reggio Emilia	Modena
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	U.O.C. Malattie Infettive Tor Vergata, Policlincio Tor Vergata	Roma
Italy	Hospital of Vipiteno	Vipiteno
Spain	Ace Alzheimer Center	Barcelona
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Private clinic Blue Healthcare	Madrid
Spain	Hospital General Universitario- Servicio de Medicina Interna	Valencia
Spain	Hospital Royo Villanova	Zaragoza
Switzerland	REHAB Clinic for Neurorehabilitation and Paraplegiology	Basel
Switzerland	Inselspital Bern University Hospital Bern	Bern
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Geneva University Hospital	Geneva
Switzerland	Centre hospitalier du Valais Romand (CHVR) - Hôpital du Valais	Sion

Sponsors (1)

Lead Sponsor	Collaborator
GeNeuro SA

Countries where clinical trial is conducted

Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in fatigue in PASC patients	Occurrence of an improvement in fatigue, measured by a decrease of =3 points in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a) score, at Week 24 as compared to baseline.	24 weeks
Secondary	Fatigue	Change from baseline to Week 24 in the Severity of fatigue as measured by the PROMIS Fatigue SF 7a score	24 weeks
Secondary	Cognitive function	Change from baseline to Week 24 in 5 domain scores (verbal memory test, digit sequencing test, Token Motor Test, verbal semantic and letter fluency, and Tower of London) as measured by BAC tests	24 weeks
Secondary	Cognitive function	Change from baseline to Week 24 in Symbol Digit Modalities Test (SDMT) score	24 weeks
Secondary	Cognitive function	Change from baseline to Week 24 in Cognitive function as measured by the composite score of the BAC excluding symbol coding test	24 weeks
Secondary	Cognitive function	Change from baseline to Week 24 in Cognitive function as measured by the Perceived Deficits Questionnaire, 20 items (PDQ-20)	24 weeks
Secondary	Anxiety	Change from baseline to Week 24 in Severity of anxiety as measured by the Generalized Anxiety Disorder, 7 Items (GAD 7)	24 weeks
Secondary	Depression	Change from baseline to Week 24 in Severity of depression as measured by the Patient Health Questionnaire, 9 Items (PHQ-9)	24 weeks
Secondary	Overall quality of Life	Change from baseline to Week 24 in Overall quality of life as measured by the European Quality of Life 5 Dimensions, 5 Levels (EQ5D-5L)	24 weeks
Secondary	Functional impairment	Change from baseline to Week 24 in Level of functional impairment as measured by the Sheehan Disability Scale (SDS)	24 weeks
Secondary	Post-COVID-19 Functional Status	Change from baseline to Week 24 in Post-COVID-19 Functional Status Scale (PCFS)	24 weeks
Secondary	Safety and tolerability of Temelimab in PASC patients	Incidence of serious AEs [SAEs], AEs and analysis of physical examination findings, clinical laboratory values results	24 weeks