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

• ClinicalTrials.gov Identifier: NCT05497089
• Recruitment Status: Recruiting
• First Posted: August 11, 2022
• Last Update Posted: May 10, 2023
• Sponsor: GeNeuro SA
• Information provided by (Responsible Party): GeNeuro SA

Tracking Information

• First Submitted Date: August 3, 2022
• First Posted Date: August 11, 2022
• Last Update Posted Date: May 10, 2023
• Actual Study Start Date: August 29, 2022
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2022)

Composite endpoint: improvement in cognitive impairment or fatigue in PASC patients [ Time Frame: 24 weeks ]

Occurrence of an improvement in cognitive impairment, measured by an increase of ≥0.5 z-scores in the Token Motor Test, or 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 9, 2022)

• Fatigue [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in the Severity of fatigue as measured by the PROMIS Fatigue SF 7a score
• Cognitive function [ Time Frame: 24 weeks ]
  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
• Cognitive function [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Symbol Digit Modalities Test (SDMT) score
• Cognitive function [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Cognitive function as measured by the composite score of the BAC excluding symbol coding test
• Cognitive function [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Cognitive function as measured by the Perceived Deficits Questionnaire, 20 items (PDQ-20)
• Anxiety [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Severity of anxiety as measured by the Generalized Anxiety Disorder, 7 Items (GAD 7)
• Depression [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Severity of depression as measured by the Patient Health Questionnaire, 9 Items (PHQ-9)
• Quality of Life [ Time Frame: 24 weeks ]
  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)
• Functional impairment [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Level of functional impairment as measured by the Sheehan Disability Scale (SDS)
• Post-COVID-19 Functional Status [ Time Frame: 24 weeks ]
  Change from baseline to Week 24 in Post-COVID-19 Functional Status Scale (PCFS)
• Safety and tolerability of Temelimab in PASC patients [ Time Frame: 24 weeks ]
  Incidence of serious AEs [SAEs], AEs and analysis of physical examination findings, clinical laboratory values results

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome
• 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
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Post-COVID-19 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)
• Drug: Placebo
  Placebo will be given as monthly (every 4 weeks) intravenous (IV) infusion over 24 weeks (6 infusions in total)

Study Arms

• Experimental: Temelimab 54mg/kg
  Monthly IV repeated dose in addition to standard of care
  Intervention: Drug: Temelimab 54mg/kg
• Placebo Comparator: Placebo
  Monthly IV repeated dose in addition to standard of care
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 9, 2022): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Main Inclusion Criteria:

• PASC Syndrome in accordance with NICE criteria with symptoms still occurring >12 to 96 weeks post diagnostic RT-PCR date
• 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 (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 medication (e.g., azathioprine, tacrolimus, cyclosporine, methotrexate, hydroxychloroquine, cytotoxic chemotherapy, or neutralizing antibodies against SARS-CoV-2 epitopes) or therapy with HIV protease inhibitors

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Karim KEDDAD, MD, PhD; +41 22 552 48 00; kk@geneuro.com

Contact: Nathalie BERTHUY; +41 22 552 48 00; nab@geneuro.com

• Listed Location Countries: Italy, Spain, Switzerland

Administrative Information

• NCT Number: NCT05497089
• Other Study ID Numbers: GNC-501; 2022-000618-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: GeNeuro SA
• Original Responsible Party: Same as current
• Current Study Sponsor: GeNeuro SA
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: David LEPPERT, MD; GeNeuro SA

• PRS Account: GeNeuro SA
• Verification Date: May 2023