The ExPlas Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Norwegian University Of Science And Technolology

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Sep 2021 → ongoing

Decision date (initial)

2025-01-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

St. Olavs Hospital · The Liaison Committee for Central Norway Regional Health Authority. · Central Norway Regional Health Authority · The Research Council of Norway

External identifiers

EU CT number

2024-518668-11-01

EudraCT number

2018-000148-24

ClinicalTrials.gov

NCT05068830

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Proportion of patients with adverse events after 1 year as a measure of safety and tolerability, and number of subjects who comply with the research protocol as a measure of feasibility.

Secondary objectives 1

1. Secondary endpoints of ExPlas after 1, 2 and 5 years Change in performance in the CERAD (The Consortium to Establish a Registry for Alzheimer’s Disease) 10 word Test Change in the Mini-Mental State Examination (MMSE) score Change in performance in Trail-Making test A and B Change in scores in other cognitive tests: the Clock Drawing Test, Controlled Oral Word Association Test (COWAT)-FAS, Visual Object and Space Perception (VOSP) Silhouettes Change in Clinical Dementia Rating Scale Global score and Sum of Boxes, and The Lawton Instrumental Activities of Daily Living Scale (IADL) Change in performance in the 6 minute walk-test Change in/reduced hippocampal atrophy and preservation of functional connectivity assessed by resting state functional MRI Change in score of quality-of-Life SF-36 Questionnaire Change in biomarkers in blood and cerebrospinal fluid (CSF) Change in cardiac dimensions, volumes and functional indices

Conditions and MedDRA coding

Early symptomatic phase Alzheimer's disease

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patient inclusion criteria Signed informed consent Age up to 75 years Diagnosis AD in early phase according to the IWG-2 criteria43 Decreased Aβ42 together with increased t-tau or p-tau in CSF Increased tracer retention on amyloid Positron Emission Tomography (PET) MMSE Score ≥20 Availability of a next of kin who knows the patient well and is willing to accompany the subject to all trial visits and to provide information about the patient’s functional level The patient is judged fit for participation, and capable of taking part in the treatment and follow-up procedures Ability to communicate in Norwegian or another Scandinavian language

Exclusion criteria 1

1. Patient exclusion criteria Patients will be excluded from the study if they meet any of the following criteria: Pregnancy or unwilling to use adequate birth control for the duration of and 6 months beyond study participation Defined according to Clinical Trial Facilitation Group document ‘Recommendations related to contraception and pregnancy testing in clinical trials’ Positive for Hepatitis B, Hepatitis C or HIV at screening Lack of competency to provide informed consent at inclusion Any other condition judged to interfere with the safety of the patient or the intent and conduct of the study Related to medical history Stroke Anaphylaxis Prior adverse reaction to any human blood product Any history of a blood coagulation disorder or hypercoagulability Congestive heart failure, defined as any previous heart failure hospitalisation, or current symptomatic heart failure in New York heart Association class ≥II with reduced, mid-range or preserved ejection fraction. Coagulation defect or hypercoagulopathy Uncontrolled hypertension Renal failure Prior intolerance to intravenous fluids Recent history of uncontrolled atrial fibrillation Bone marrow transplant IgA deficiency Severe protein S deficiency Thrombocytopenia (platelets <40 x 109 /L) Contraindication for Octaplasma Related to medications or other treatments Any concurrent use of anticoagulant therapy, clopidogrel or acetylsalicylic acid/dipyridamole in combination Initiation or change in the dosage of a acetylcholine esterase inhibitor (AChEI) or memantine during the trial (weeks 0–52). Participants will be urged to start on AChEI when diagnosis is communicated, and must be on a stable dose for at least 1 month prior to screening Concurrent participation in another treatment trial for AD. If there was prior participation, the last dose of the investigational agent must have been given at least 6 months prior to screening, except if the patient received placebo medication Prior or concurrent participation in amyloid antibody trials, except if the patient received placebo medication Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to screening or during the trial Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics, long-acting opioids or other medications that are judged to interfere with cognition. Intermittent treatment with short-acting benzodiazepines or atypical antipsychotics may be permitted, provided that no dose is administered within 72 hours prior to cognitive assessment Related to MRI Claustrophobia Any metallic surgical implant, like a pacemaker or chip incompatible with MRI Certain metallic implants like joint prostheses may be permitted, provided that specific manufacturer specifications are available, and that the device is known to be safe for 7T MRI. In case a patient is not eligible for the 7T scanner, the 3T scanner will be used

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients with adverse events after 1 year as a measure of safety and tolerability, and number of subjects who comply with the research protocol as a measure of feasibility.

Secondary endpoints 1

1. Change in performance in the CERAD 10 word Test Change in the Mini-Mental State Examination (MMSE) score Change in performance in Trail-Making test A and B Change in scores in other cognitive tests: the Clock Drawing Test, Controlled Oral Word Association Test (COWAT)-FAS, Visual Object and Space Perception (VOSP) Silhouettes Change in Clinical Dementia Rating Scale Global score

Investigational products

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

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Norwegian University Of Science And Technolology

Sponsor organisation

Norwegian University Of Science And Technolology

Address

Hoegskoleringen 1

City

Trondheim

Postcode

7034

Country

Norway

Scientific contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Atefe Rafiee Tari

Public contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Atefe Rafiee Tari

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 9 files

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

Application history

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