The BioFINDER 2 study - improved diagnostics and increased understanding of the pathophysiology of cognitive disorders

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

10 Apr 2017 → ongoing

Decision date (initial)

2024-09-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

General Electric Ltd. United States · Hoffman La Roche Ltd. Switzerland

External identifiers

EU CT number

2024-511842-38-00

EudraCT number

2017-000094-36

ClinicalTrials.gov

NCT03174938

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

Study the diagnostic accuracy of Tau PET (18F-RO6958948) and Vizamyl (18F-Flutemetamol) for identifying healthy elderly individuals and patients with subjective or objective mild cognitive symptoms who are at high risk of subsequent development of dementia due to Alzheimer's disease (AD) or other neurodegenerative disorders.

Secondary objectives 1

1. Study whether Tau pathology (visualized with 18F-RO6958948) or amyloid pathology (visualized using Vizamyl) in non-demented subjects affects functional and structural neuronal connectivity (visualized with MRI; i.e. resting state functional MRI, Arterial Spin Labeling, Diffusion Tensor Imaging, Kurtosis etc). - Study whether CSF biomarkers (especially P-tau, total-tau and oligomeric tau, but also markers of neuroinflammation) are associated with 18F-RO6958948 retention visualized with PET. - Study whether Tau pathology can precede amyloid pathology (visualized using Vizamyl) in preclinical AD, or whether Tau-pathology is always a consequence of amyloid accumulation. - Establish cut offs for pathological PET-scans in a healthy population.

Conditions and MedDRA coding

Neurodegenerative disorders with Tau-pathology; including, but not limited to, Alzheimer's disease, progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration and mild cognitive impairment.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Healthy elderly subjects - No cognitive symptoms reported by study participant
2. Healthy elderly subjects - Normal performance on cognitive tests
3. Healthy elderly subjects - General cognition and functional performance preserved such that a diagnosis of MCI or dementia cannot be made by physician at the time of the baseline visit
4. Mild cognitive impairment/dementia - Cognitive symptoms reported by patient and/or informant
5. Mild cognitive impairment/dementia - General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by physician at the time of the baseline visit (MCI)
6. Mild cognitive impairment/dementia- General cognition and functional performance fulfilling a diagnosis of dementia at the time of the baseline visit (Dementia group)
7. All - Between 20 and 100 years of age
8. All - Fluent in Swedish
9. All - Agrees to at least one lumbar puncture, MRI scan of the brain and neuropsychological testing.

Exclusion criteria 5

1. All - Major depression as described in DSM-IV
2. All - History of schizophrenia or other recurrent psychotic disorder
3. All - History of alcohol or substance abuse or dependence within the past 5 years
4. All - Diseases that will make study participation difficult, such as terminal cancer or significant heart failure
5. All - Certain neurologic diseases, such as Huntington's disease, normal pressure hydrocephalus, brain tumor, subdural hematoma, multiple sclerosis, or persistent neurologic deficits or known structural brain abnormalities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Detection of specific signal of 18F-RO6958948 or 18F-Flutemetamol in patients with neurodegenerative disease or healthy volunteers.

Secondary endpoints 3

1. - 18F-RO6958948 or 18F-Flutemetamol PET brain:cerebellar uptake ratios measured with a priori VOI analysis in subjects with neurodegenerative disease compared to healthy volunteers
2. - Associations of 18F-RO6958948 or 18F-Flutemetamol brain uptake ratios measured by VOI analysis with other diagnostic methods, including CSF biomarkers, cognitive tests and MRI findings
3. - Regional differences in distribution of 18F-RO6958948 or 18FFlutemetamol brain uptake between different neurodegenerative disease conditions

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Minneskliniken, Skåne University Hospital

Public contact point

Organisation

Region Skane

Contact name

Minneskliniken, Skåne University Hospital

Locations

1 EU/EEA country · 1 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 11 files

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

Application history

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