Efficacy of efgartigimod alfa as add‑on to intravenous methylprednisolone for moderate‑to‑severe attacks in patients with multiple sclerosis, NMOSD or MOGAD

The primary objective is to evaluate the efficacy of efgartigimod compared with placebo as an add‑on to standard intravenous methylprednisolone therapy in patients experiencing moderate‑to‑severe attacks of clinically isolated syndrome/relapsing‑remitting multiple sclerosis, AQP4‑positive neuromyelitis optica spectrum disorder, or MOG‑associated disease, thereby determining whether the combination improves acute attack outcomes in demyelinating diseases.

Secondary objectives address additional clinical and biological endpoints:

• Rate of escalation to rescue attack therapy.
• Rate of early remission following an attack.
• Timing and precise grade of clinical improvement.
• Risk of early relapses.
• Overall quality of life, including vision‑related quality of life in patients with optic neuritis.
• Changes in pathogenic AQP4/MOG autoantibody concentrations and biomarkers reflecting neuronal and astrocytic damage.
• Total cumulative dose of intravenous methylprednisolone administered.
• Safety profile of the investigational product when combined with standard therapy.

The trial enrolled adult participants aged ≥ 18 years of any gender, including male, female, and inter/diverse individuals; the sponsor did not provide the total number of participants. Subjects were selected based on a documented clinical attack consistent with clinically isolated syndrome (CIS), RRMS, AQP4‑positive neuromyelitis optica spectrum disorder, or MOG‑associated disease, with moderate‑to‑severe severity. Key inclusion criteria included the ability to initiate the investigational product within 10 days of attack onset and no later than the fifth intravenous methylprednisolone dose, a pre‑attack EDSS ≤ 6.0, an attack‑phase EDSS of 3.0–7.5, and provision of signed informed consent with capacity to comply with protocol requirements. No specific dietary, physical activity, or habit‑related restrictions were detailed in the available information.

A multicentre, randomized, double-blind, placebo-controlled phase II/III trial will evaluate the efficacy of EFGARTIGIMOD ALFA as a first‑line add‑on to standard intravenous methylprednisolone (IVMP) in patients ≥ 18 years experiencing a moderate‑to‑severe attack of demyelinating diseases (CIS, RRMS, AQP4‑positive NMOSD, or MOGAD). After obtaining informed consent, participants undergo a screening visit to confirm eligibility, including documentation of pre‑attack EDSS and target neurological deficits. Eligible subjects receive the first infusion of the investigational product or matching placebo within 10 days of attack onset and no later than the fifth IVMP dose. Subsequent study visits are scheduled on days 4, 10, 21, 28, and 84 for efficacy and safety assessments, with the day 84 visit serving as the end‑of‑study evaluation. The primary endpoint is the proportion of patients achieving complete remission of target neurological deficits by day 84 without rescue therapy. Secondary assessments include rescue‑therapy avoidance, remission at earlier time points, changes in EDSS, visual acuity, functional tests, biomarker levels, and quality‑of‑life scores. Participants remain in the trial for approximately 12 weeks; early termination may occur if rescue attack therapy (plasmapheresis or immunoadsorption) is required, if serious adverse events arise, if consent is withdrawn, or if protocol non‑compliance is identified.

The investigational product, efgartigimod alfa, is supplied as an intravenous infusion solution and administered at a dose of 2400 per infusion. The infusion is delivered via the intravenous route and is given according to the study‑specified schedule, with each dosing event recorded in the infusion log to ensure adherence to the protocol.

The control arm receives a matching placebo formulated to be indistinguishable from the active infusion. The placebo is administered by intravenous infusion using the same volume, rate, and schedule as the active product, and compliance is similarly documented in the infusion log.

All participants receive standard‑of‑care therapy consisting of intravenous methylprednisolone (IVMP) as a first‑line treatment for moderate‑to‑severe attacks of demyelinating diseases. IVMP is given according to the established dosing regimen for acute attacks, and timing of administration relative to the study drug or placebo infusion is recorded to maintain consistent exposure across treatment groups.

The efficacy evaluation will focus on the proportion of participants achieving complete remission of targeted neurological deficits (TNDs) by day 84 after the first investigational medicinal product (IMP) administration without rescue attack therapy, constituting the primary endpoint. Remission is defined as a return to at least pre‑attack levels in all TND functional system scores (FSS) and habitual corrected high‑contrast visual acuity (HCVA). Assessments will be performed at predefined visits, with the primary outcome determined at the day 84 visit.

Secondary efficacy measures include: the proportion of patients not requiring rescue attack therapy (plasmapheresis or immunoadsorption) by day 28; remission status at days 10 and 28; rates of almost complete remission of TNDs at days 10, 28, and 84; and changes from baseline in neurological function scores at days 10, 28, and 84. Neurological function will be quantified using validated instruments such as the Expanded Disability Status Scale, main TND FSS, ambulation score, best‑corrected HCVA, low‑contrast visual acuity (LCVA), Nine‑Hole Peg Test, and Timed 25‑Foot Walk. Visual acuity will be measured at days 28 and 84, while quality‑of‑life will be assessed with the EQ‑5D and, for optic neuritis attacks, the NEI VFQ‑25 at days 28 and 84. Immunological and neurodegenerative biomarkers—including total IgG subclasses, AQP4‑IgG, MOG‑IgG, Neurofilament light chain, glial fibrillary acidic protein, and complement proteins C3 and C4—will be sampled at days 4, 10, 21, 28, and 84. Cumulative IVMP dosage will be recorded through day 84. All assessments will be conducted according to the trial schedule and analyzed in accordance with the predefined statistical analysis plan.