A trial to find the effect of Ginkgo biloba extract EGb 761® and how safe it is in participants with cognitive impairment associated with post COVID-19 syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dr. Willmar Schwabe GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Mar 2025 → ongoing

Decision date (initial)

2025-01-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Dr. Willmar Schwabe GmbH & Co. KG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the effect of EGb 761® (240mg QD) compared to placebo on objective cognitive outcomes in participants with cognitive impairment associated with PCS

Secondary objectives 1

1. 1. To evaluate the effect of EGb 761® (240mg QD) compared to placebo on neuropsychiatric outcomes in participants with cognitive impairment associated with PCS. 2. To evaluate the effect of EGb 761® (240mg QD) compared to placebo on neurosensory outcomes in participants with cognitive impairment associated with PCS. 3. To evaluate the effect of EGb 761® (240mg QD) compared to placebo on global and functional outcomes in participants with cognitive impairment associated with PCS. 4. To evaluate the safety of EGb 761® (240mg QD) compared to placebo.

Conditions and MedDRA coding

COGNITIVE IMPAIRMENT ASSOCIATED WITH POST-COVID-19 SYNDROME

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. • Male or female outpatient, aged ≥18 years at the time of signing the ICF
2. • 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
3. • 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
4. • Presence of persisting subjective cognitive problems for at least 2 months, associated with PCS and arising after the SARS-CoV-2 infection
5. • 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)
6. • 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 7

1. • Participants who required mechanical ventilation at an intensive care unit during the acute SARS CoV 2 infection
2. • Presence of haemorrhagic diatheses, coagulation disorder, gastric or duodenal ulcer
3. • 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
4. • 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
5. • 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
6. • Intake of Ginkgo biloba products within the last 12 weeks
7. • 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Change from baseline to Week 6 and Week 12 in the following test scores: • Digit span forward and backward test • Verbal fluency test • TMT (A + B) • CVLT • d2-R
2. Change from baseline to Week 6 and Week 12 in the following questionnaire scores: • GAD-7 test • PHQ-9 tes
3. Change from baseline to Week 6 and Week 12 in the 11-point box scale score for vertigo and tinnitus
4. Change from baseline to Week 6 and Week 12 in the following test/questionnaire scores: • CGI-S • PCFSS • MFIS • mPEM-DSQ • SBQ-LC test • CGI-I at Week 6 and Week 12
5. Number of patients with AEs, ADRs and SAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Willmar Schwabe GmbH & Co. KG

Sponsor organisation

Dr. Willmar Schwabe GmbH & Co. KG

Address

Willmar-Schwabe-Strasse 4, Durlach Durlach

City

Karlsruhe

Postcode

76227

Country

Germany

Scientific contact point

Organisation

Dr. Willmar Schwabe GmbH & Co. KG

Contact name

Anna Wacker

Public contact point

Organisation

Dr. Willmar Schwabe GmbH & Co. KG

Contact name

Anna Wacker

Third parties 4

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications