Efgartigimod as a first line attack therapy in demyelinating diseases of the central nervous system

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Hochschule Hannover

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)

2026-06-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Argenx BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the efficacy of efgartigimod compared with placebo as add-on to standard intravenous methylprednisolone (IVMP) therapy in patients with moderate-to-severe attacks† of CIS/RRMS, AQP4+ NMOSD or MOGAD

Secondary objectives 8

1. 1. To assess the effect of efgartigimod add-on therapy on the rate of escalation to rescue attack therapy
2. 2. To assess the effect of efgartigimod add-on attack therapy on the rate of early remission following an attack
3. 3. To assess the effect of efgartigimod add-on attack therapy on the timing and precise grade of the clinical improvement
4. 4. To assess the effect of efgartigimod add-on attack therapy on the risk of early relapses#
5. 5. To assess the effect of efgartigimod as an add-on attack therapy on overall quality of life for all patients, and specifically on vision-related quality of life in patients with ON
6. 6. To evaluate the impact of efgartigimod as an add-on therapy on the levels of pathogenic AQP4/MOG-autoantibodies and biomarkers reflecting the severity of neuronal and astrocytic damage following the attack
7. 7. To assess the effect of add-on therapy with efgartigimod on the total cumulative IVMP dose
8. To evaluate the safety profile of efgartigimod as an add-on to standard IVMP attack therapy in moderate-to-severe attacks of CIS/RRMS, AQP4+ NMOSD or MOGAD

Conditions and MedDRA coding

Demyelinating diseases

Regulatory references

Plan to share IPD

Yes

IPD plan description

Data will be shared on reasonable request to the principal investigator.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Subjects aged ≥18 years of any gender (male, female, inter/divers) are eligible, biological sex assigned at birth will be documented at screening
2. 2. Presence of a clinical attack† consistent with one of the following diagnoses according to established criteria: CIS§ (1), RRMS (2), AQP4+ NMOSD (3), MOGAD (4)
3. 3. Provision of signed and dated written informed consent by the subject or an impartial witness, and the ability to comply with protocol requirements
4. 4. Subjects are eligible if the first Investigational Medicinal Product (IMP) infusion can be initiated within 10 days of attack onset and no later than the 5th IVMP administration
5. 5. Pre-attack EDSS (Expanded Disability Status Scale) ¶, including target neurological deficits (TND)‡ functional system scores (FSS), and corrected HCVA (High Contrast Visual Acuity) in case of ON (Optic Neuritis; habitual or best-corrected) must be either documented or retrospectively assessable
6. 6. Pre-attack EDSS¶ ≤6.0
7. 7. EDSS during current attack 3.0 - 7.5
8. 8. At least moderate attack severity, defined as the presence of at least one of the following TND‡ at screening: · for pyramidal, brainstem, cerebellar subscales ΔFSS⁑ >2.0 and minimal FSS ≥3.0 · for sensory subscales ΔFSS⁑>2.0 and minimal FSS ≥4.0 · in ON HCVA ≤20/200 (≥1.0 logMAR); if documented previous visual deficits Δ⁑ ≥2 lines ETDRS (Early Treatment Diabetic Retinopathy Study; 0.2 logMAR); ⁑ Δ is defined as the change from the pre-attack baseline (most recent assessment prior to the current attack during remission) to the score assessed at screening

Exclusion criteria 13

1. 1. Current attack presenting with predominant involvement of the cerebral FSS at screening
2. 2. Use of the following previous or concomitant therapies a. anti-FcRn therapy ≤3 months before screening b. IVMP*; plasma exchange or immunoadsorption; intravenous, intramuscular or subcutaneous IgG received ≤4 weeks before screening c. any form of CAR T-cell therapy or hematopoietic stem cell transplantation (HSCT) before screening; * except for the administration of ≤5 IVMP for the current attack
3. 3. For patients without best-corrected HCVA data within 12 months before onset of the current attack any visually significant ocular pathology (e.g., retinal diseases, cataracts, glaucoma, etc.) in the affected eye constitutes an exclusion criterion; congenital color-blindness is not disqualifying
4. 4. Clinically active or chronic uncontrolled infection (bacterial, fungal or viral), including patients who test positive for an active viral infection at screening with: a. Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with CD4 ≤200 cells/mm3 b. Hepatitis B Virus (HBV): serologic panel test results indicative of an active (acute or chronic) infection c. Hepatitis C Virus (HCV): serology positive for anti-HCV antibodies
5. 5. Known common variable immunodeficiency
6. 6. History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years before screening. Adequately treated participants with the following cancers may be included at any time: a. Basal cell or squamous cell skin cancer b. Carcinoma in situ of the cervix c. Carcinoma in situ of the breast d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
7. 7. Live or live-attenuated vaccine received <4 weeks before screening. Receiving an inactivated, sub-unit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary, however, these vaccines must not be administered within 48 hours before IMP infusion
8. 8. Pregnant or lactating state or intention to become pregnant during the study
9. 9. Severe renal impairment with eGFR <30 mL/min/1.73 m2 at screening
10. 10. Known hypersensitivity to efgartigimod, methylprednisolone, prednisone and any contained excipients of the IMPs
11. 11. Clinically significant disease, recent major surgery within 3 months prior to screening, or planned major surgery during the study period
12. 12. Any other medical condition that, in the investigator’s opinion, would confound the accurate assessment of clinical symptoms or put the participant at undue risk
13. 13. Participation in another clinical trial involving investigational drugs or medical devices at the time of enrollment, or participation in such a trial within 30 days prior to enrollment (or within five half-lives of the investigational product, whichever is longer), if this may interfere with the endpoints of the present study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients who achieve complete remission of TNDs by day 84* after the first IMP administration without rescue attack therapy. Complete remission is defined as a return to at least pre-attack levels in all TNDs FSS and HCVA

Secondary endpoints 12

1. 1. Proportion of patients not requiring rescue attack therapy (plasmapheresis (PLEX), immunoadsorption (IA)) by day 28 after first IMP administration
2. 2. Proportion of patients achieving complete remission of TNDs at day 10 and 28 without rescue attack therapy
3. 3. Proportion of patients achieving almost complete remission of TNDs by day 84* without rescue attack therapy; * Complete or almost complete remission can be achieved at another visit prior to day 84
4. 4. Proportion of patients achieving almost complete remission of TNDs (according to Appendix 1) at day 10 and 28 without rescue attack therapy
5. 5. Change in attack-affected neurological function scores from baseline at day 10, 28, and 84, including: ○ Overall EDSS (Expanded Disability Status Scale) ○ Main TND FSS‡‡ ○ Ambulation score ○ Habitual corrected high-contrast visual acuity (HCVA) ○ Nine-Hole Peg Test (9HPT) ○ Timed 25-Foot Walk (T25FW)
6. 6. Best-corrected high-contrast visual acuity (HCVA) and habitual corrected low-contrast visual acuity (LCVA) at day 28, 84
7. 7. Early relapses rates within 3 months (day 84)
8. 8. Change from baseline in quality-of-life scores at day 28 and 84, including: ○ General quality of life (EQ-5D) ○ Vision-related quality of life (NEI VFQ-25) if ON attack
9. 9. Change from baseline in immunological and neurodegenerative biomarkers at day 4, 10, 21, 28 and 84 post-treatment, including: ○ Total IgG and IgG subclasses (IgG1–4) ○ AQP4-IgG and MOG-IgG titers ○ Neurofilament light chain (NfL) ○ Glial fibrillary acidic protein (GFAP)
10. 10. Change from baseline in immunological biomarkers at day 4, 10 post-treatment, including: ○ Complement proteins (C3, C4)
11. 11. Cumulative dosage of IVMP at day 84
12. Assessment of safety: Incidence rates of adverse events (AEs), serious adverse events (SAEs) and adverse event of special interest (AESIs) by day 28 after treatment onset and during the complete trial

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Hochschule Hannover

Sponsor organisation

Medizinische Hochschule Hannover

Address

Carl-Neuberg-Strasse 1, Gross Buchholz Gross Buchholz

City

Hanover

Postcode

30625

Country

Germany

Scientific contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Klinik für Neurologie

Public contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Klinik für Neurologie

Third parties 3

Locations

2 EU/EEA countries · 22 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 15 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