Refined and quantified dry extract of Ginkgo biloba leaves (35-67:1) quantified to 22.0 to 27.0 % of flavonoids (expressed as flavone glycosides), 2.8 to 3.4 % of ginkgolides A, B and C, and 2.6 to 3.2 % of bilobalide. Extraction solvent: acetone 60% (m/m) for Cognitive impairment associated with post-COVID-19 syndrome|Post-acute COVID-19 syndrome

Inclusion criteria

• {"criterion_text":"- • Male or female outpatient, aged ≥18 years at the time of signing the ICF"}
• {"criterion_text":"- • Diagnosis of PCS based on the World Health Organisation (WHO) definition, requires a history of probable or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and PCS continuing at least beyond 3 months from the onset of coronavirus disease (COVID-19) symptoms. Symptoms should last for at least 2 months and cannot be explained by an alternative diagnosis; symptoms have an impact on everyday functioning, as indicated by a physician-rated post COVID functional status scale (PCFSS) score between 2 and 4; symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness, and they may fluctuate or relapse over time"}
• {"criterion_text":"- • History of probable or confirmed SARS-CoV-2 infection, confirmed by at least one of the following: positive polymerase chain reaction (PCR) test at the time of infection, positive antigen test at the time of infection along with clinical or epidemiological criteria, physician’s diagnosis based on a positive PCR or antigen test along with clinical or epidemiological criteria, presence of immunoglobulin G-antibody to the viral nucleocapsid antigen (anti-N IgG) antibodies, or presence of immunoglobulin G antibody to the viral spike antigen (anti-S IgG) antibodies in unvaccinated participants"}
• {"criterion_text":"- • Presence of persisting subjective cognitive problems for at least 2 months, associated with PCS and arising after the SARS-CoV-2 infection"}
• {"criterion_text":"- • Objective cognitive impairment, defined as deficits in at least one of the following 2 domains of cognition: memory (assessed by the California Verbal Learning Test [CVLT], long delay-free recall, below the 50th percentile for age and education) and executive functioning (assessed by the Trail-Making Test part B (TMT)-B, below the 50th percentile for age and education)"}
• {"criterion_text":"- • Concomitant mild to moderate anxiety or depressive symptoms, defined as a Generalized Anxiety Disorder-7 (GAD-7) score between 5 to 14 and/or Patient Health Questionnaire-9 (PHQ-9) score between 5 to 19."}

Exclusion criteria

• {"criterion_text":"- • Participants who required mechanical ventilation at an intensive care unit during the acute SARS CoV 2 infection"}
• {"criterion_text":"- • Presence of haemorrhagic diatheses, coagulation disorder, gastric or duodenal ulcer"}
• {"criterion_text":"- • Presence of acute or chronic neurologic diseases within the last 12 months, such as stroke, transient ischemic attack (TIA), Parkinson’s disease, Alzheimer’s disease, seizure disorders, craniocerebral trauma, brain haemorrhage, multiple sclerosis, or cognitive impairment or dementia before acute COVID-19"}
• {"criterion_text":"- • Presence of acute or chronic psychiatric diseases within the last 12 months, including severe depression (PHQ-9 ≥20), severe anxiety (GAD-7 ≥15), significant primary sleep disorder, attention deficit hyperactivity disorder, bipolar disorder, substance use disorders, addictive behaviours, or schizophrenia. Mild to moderate psychiatric symptoms triggered by the SARS-CoV-2 infection will be allowed"}
• {"criterion_text":"- • Presence of severe or unstable internal disorders, such as cancer (with exceptions), active bacterial infections or known HIV infection, uncontrolled diabetes mellitus, uncontrolled arterial hypertension, known cardiac arrhythmia (Lown-classification IVb and V), heart failure NYHA III or IV, severe coronary heart disease, unstable angina pectoris, recent heart attack within last 6 months"}
• {"criterion_text":"- • Intake of Ginkgo biloba products within the last 12 weeks"}
• {"criterion_text":"- • History of postexertional malaise (PEM) persisting a week or longer in response to an exertion comparable to the planned site visits within the last 8 weeks"}

Primary endpoints

• {"endpoint_text":"- Change from baseline to Week 6 and Week 12 in the following test scores: •\tDigit span forward and backward test •\tVerbal fluency test •\tTMT (A + B) •\tCVLT •\td2-R","definition_or_measurement_approach":"Change from baseline to Week 6 and Week 12 measured using listed cognitive tests: Digit span forward and backward, Verbal fluency test, Trail-Making Test A+B, California Verbal Learning Test (CVLT), and d2-R attention test."}
• {"endpoint_text":"- Change from baseline to Week 6 and Week 12 in the following questionnaire scores: •\tGAD-7 test •\tPHQ-9 tes","definition_or_measurement_approach":"Change from baseline to Week 6 and Week 12 measured by GAD-7 (Generalized Anxiety Disorder-7) and PHQ-9 (Patient Health Questionnaire-9) questionnaire scores."}
• {"endpoint_text":"- Change from baseline to Week 6 and Week 12 in the 11-point box scale score for vertigo and tinnitus","definition_or_measurement_approach":"Change from baseline to Week 6 and Week 12 measured using an 11-point box scale for vertigo and for tinnitus."}
• {"endpoint_text":"- Change from baseline to Week 6 and Week 12 in the following test/questionnaire scores: •\tCGI-S •\tPCFSS •\tMFIS •\tmPEM-DSQ •\tSBQ-LC test • CGI-I at Week 6 and Week 12","definition_or_measurement_approach":"Change from baseline to Week 6 and Week 12 measured by clinician/global and functional scales: CGI-S, PCFSS, MFIS, mPEM-DSQ, SBQ-LC; plus CGI-I assessed at Week 6 and Week 12."}
• {"endpoint_text":"- Number of patients with AEs, ADRs and SAEs","definition_or_measurement_approach":"Count of participants experiencing adverse events (AEs), adverse drug reactions (ADRs) and serious adverse events (SAEs) during the study period."}

Methods

• Social media campaigns (Social-Media documents for DE, ES, PL) targeting individuals with post-COVID cognitive symptoms
• SMS messaging (SMS documents for DE and PL) to reach potential participants
• Email outreach (Email documents for DE, ES, PL) for recruitment contact
• Landing pages and mobile landing pages (Landing Page_DEU_GER, MOBILE Landing Page) to capture interested participants
• Pre-screener materials (Pre-screener documents) for eligibility pre-screening
• Keyword search and online display/carousel ads (Keyword-Search, Carousel) to reach target audience searching post-COVID cognitive issues
• Doctor-to-patient letters and Doctor-to-Doctor letters to engage healthcare providers and refer eligible patients
• URLs and web-based fact sheets, recruitment brochures, press materials, and fact sheets to inform public and clinicians

Poland

Earliest CTIS Part Ii Submission Date

19-12-2024

Latest Decision Or Authorization Date

10-02-2025

Processing Time Days

53

Number Of Sites

4

Number Of Participants

160

Spain

Earliest CTIS Part Ii Submission Date

13-01-2025

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

434

Number Of Sites

3

Number Of Participants

120

Germany

Earliest CTIS Part Ii Submission Date

27-12-2024

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

461

Number Of Sites

9

Number Of Participants

120

Primary sponsor

Full Name

Dr. Willmar Schwabe GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Pharmaceutical Product Development Spain S.L.

Responsibilities

sponsorDuties codes: 1,11,12,13,14,2,5,6,8,9 (as listed)

Name

4g Clinical LLC

Responsibilities

sponsorDuties code: 3 (as listed)

Name

Medidata Solutions Inc.

Responsibilities

sponsorDuties codes: 6,7 (as listed)

Name

Scout Clinical

Responsibilities

sponsorDuties code: 15 (Patient reimbursements in Spain)

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: 6, 7 (as listed in CTIS third-party entry); contact email Jonathan.CHARLES@3ds.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Pharmaceutical Product Development Spain S.L.","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 13, 14, 2, 5, 6, 8, 9 (as listed in CTIS third-party entry); contact email EUCTRInquiry.sm@thermofisher.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"sponsorDuties code: 3 (as listed in CTIS third-party entry); contact email ewest@4gclinical.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties code: 15 (Patient reimbursements in Spain); contact email ClientCompliance@scoutclinical.com","organisation_type":"Hospital/Clinic/Other health care facility"}