A double-blinded, randomized, placebo-controlled, multi-center trial of Efgartigimod in autoimmune dementia (EfgaDem)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-06-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Argenx BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To investigate the efficacy of 52 weeks treatment with the FcRn inhibitor Efgartigimod in comparison to placebo regarding the cognitive impairment in patients with autoimmune dementia.

Secondary objectives 1

1. Secondary objectives include an extensive evaluation of cognitive impairment using a neuropsychological test battery, a quality of life questionnaire and assessment of independent activities of daily living as well neuropsychiatric evaluation from baseline to 53 weeks after administration of the first dose of Efgartigimod. Further secondary objectives are laboratory parameters and include serum and CSF immune cells as well as possible changes in the autoantibody repertoire. All adverse events and serious adverse events are monitored throughout the whole duration of the trial.

Conditions and MedDRA coding

Autoimmune dementia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male and female subjects ≥ 40 years of age
2. Expert diagnosis of progressive cognitive impairment or dementia for more than 3 months
3. 10 < MoCA ≤ 25
4. Presence of anti-brain autoantibodies in serum and/or CSF
5. Age ≥ 40 years
6. Speaks German at a level that, as determined by the investigator, allows to understand the patient information and to reliably perform the neuropsychological assessments
7. Written consent to participate in the study
8. The patient is capable to attend study visits
9. Vaccination according to STIKO recommendations (incl. COVID-19 vaccination)

Exclusion criteria 18

1. Dysfunction (other than neurodegenerative or immunological) that could distort or obscure the diagnosis of dementia such as vitamin deficiency or hypothyroidism
2. Participation in any other investigational drug study or exposure to an investigational drug within 5 half-lives of the study drug at baseline
3. MRI findings (macro bleeding, malignant tumors)
4. Treatment with B-cell depleting therapy in the last 6 months
5. History of recurrent or chronic infections or with underlying diseases which may further predispose patients to serious infection
6. Sexually active male and female patients of reproductive potential (female patients/female partners of patients less than 12 months postmenopausal) who do not use highly effective contraception methods (pearl index <1) during treatment
7. Hypersensitivity to the active substance and/or pharmaceutical excipients
8. Known cytokine release syndrome after infusions
9. Pregnancy or lactation
10. HIV infection
11. Active, severe infections (e.g. sepsis and opportunistic infections)
12. History of chronically active hepatitis including active or chronic hepatitis B, acute or chronic hepatitis C
13. Clinically significant infection involving intravenous administration of antibiotics and hospitalization in the 4 weeks prior to the screening visit
14. Serious impairment of the immune system
15. Severe disease in the renal, cardiovascular or hematological system
16. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the trial or poses any added risk for the patient
17. Severe active psychiatric illness
18. Contraindications against MRI examination (e.g. wearers of pacemakers, deep brain stimulators, cerebrospinal fluid shunt valves, very large tattoos, metal splinter injuries and implants containing metal in the body)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cognitive impairment: MoCA: change from baseline to 53 weeks. (dichotomized version of the change of the score ≥0 or <0).

Secondary endpoints 7

1. MoCA: Evaluation of change in continuous score from baseline to week 13, 27 and 53
2. Neuropsychological tests: change from baseline to week 13 and 53
3. Quality of Life: change from baseline to week 13 and 53
4. Activities of Daily Living: change from baseline to week 13 and 53
5. Reduction of autoantibodies from baseline to week 13 and 53
6. Partial normalization of further laboratory parameters from baseline to week 53
7. Serum and cerebrospinal fluid analyses with cell count, cytology, protein, glucose, lactate and infection markers

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Sponsor organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Address

Venusberg-Campus 1/99, Venusberg Venusberg

City

Bonn

Postcode

53127

Country

Germany

Scientific contact point

Organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Contact name

Prof. Dr. Harald Prüß

Public contact point

Organisation

Deutsches Zentrum Fuer Neurodegenerative Erkrankungen e.V.

Contact name

Dr. Friederike Ufer

Third parties 5

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 19 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