Subjects from 18 to 60 years old with a diagnosis of a unilateral Acute Optic Neuritis with a demyelinating origin, whose symptoms have appeared in the last 10 days before randomization and whose expanded disability status scale score is between 0 and 5.5
Conditions
Interventions
Product Name: ACT-01
Product Code: ACT-01
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: ACT-01
Current Sponsor code: ACT-01
Other descriptive name: BN201
Concentration uni
Sponsors
ACCURE TX FRANCE SASU
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The inclusion criteria are: - Aged 18-60 years - Diagnosed with a unilateral acute optic neuritis with a demyelinating origin - Onset of visual loss symptoms in the last 10 days before randomization - Expanded Disability Status Scale (EDSS) score between 0 and 5.5 - Able to understand study information and provide signed written informed consent - Affiliated to/beneficiary of the French Health Social Security System Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Optic neuropathy of non-demyelinating origin: infectious diseases, ischemic, traumatic, tumor or other • Known Neuromyelitis optica with autoantibodies against aquaporin-4 (AQP4-Abs) • Patients with widespread and symmetric white matter alterations in the screening MRI suggestive of other demyelinating disorders (e.g. metabolic disorders, mitochondrial disorders) • Active, chronic disease (or stable but treated with immune therapy) of the immune system other than Multiple Sclerosis (MS) (e.g. Sjögren’s disease, systemic lupus erythematosus) or with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency) • An alternative cause of visual loss (e.g. compressive or infiltrative lesion of the optic nerve, infections, genetic forms of visual loss. • Diagnosed with macular oedema, severe myopia (>6 d) or other disease of the retina at inclusion • Known diabetic retinopathy • Known glaucoma • Mean ganglion cell inner plexiform layer (GCIPL) thickness measured on ocular coherence tomography (Cirrus HD-OCT) below 65µm at inclusion in the affected eye • Difference in mean GCIPL thickness measured on Cirrus HD-OCT larger than 20µm between the 2 eyes, when the thinnest GCIPL is measured in the affected eye • Treatment started with any disease modifying therapy (DMT) for MS within the last 12 weeks • Requiring an anticipated switch of DMT within 3 months after inclusion • Treated with: - Class Ia (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, stalol) anti-arrhythmic drugs at inclusion - Concurrently treated with heart-rate-lowering drugs at inclusion (e.g.: ß blockers, heart rate lowering Ca2+ channel blockers (e.g. verapamil, diltiazem or ivabradine), digoxin, cholinesterase inhibitors agents, pilocarpine or S1P inhibitors) - S1P modulators (e.g. fingolimod, siponimod), anti-CD20 antibodies (e.g. rituximab, ocrelizumab), natalizumab, cladribine and alemtuzumab • Treatment for MS or Myelin oligodendrocyte glycoprotein–immunoglobulin G (MOG-IgG) associated disorder (MOGAD) other than : Interferon beta, Glatiramer acetate, Dimethyl fumarate, Teriflunomide, Mycophénolate mofetil, Azathioprine • Any severe cardiac disease or significant findings on the screening ECG • Past history of convulsion and/or seizure other than petit mal • Known history of, or concomitant severe hepatic, gastrointestinal, cardiovascular, respiratory, hematological, renal, dermatological or psychiatric disease or substance abuse or any condition that, in the opinion of the Investigator might interfere with the evaluation of study treatment or warrant exclusion • Patients who, in the opinion of the Investigator, have any clinically relevant findings that warrant exclusion. Examples of clinically relevant problems include, but are not limited to, serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs and any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study • History of malignancy within 5 years, other than effectively treated carcinoma in-situ of the cervix, or adequately treated non-metastatic squamous or basal cell carcinoma of the skin • Active, chronic diabetes or uncontrolled hypertension • Active systemic bacterial, viral or fungal infections, including tuberculosis • Known Se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the safety and tolerability of ACT-01 versus placebo at month 6 in subjects with acute optic neuritis (AON);Secondary Objective: The main secondary objective is: • To compare the efficacy of ACT-01 versus placebo on the retinal layers’ thickness in the affected eye at month 1, month 3, month 6 and month 12; The other secondary objectives are: • To compare the efficacy of ACT-01 versus placebo on clinical vision parameters in the affected eye at month 1, month 3, month 6 and month 12; • To compare the efficacy of ACT-01 versus placebo on electrophysiological parameters in the affected eye at month 3, month 6 and month 12; • To compare the efficacy of ACT-01 versus placebo on neurological parameters; • To compare the safety of ACT-01 versus placebo at month 12 • To characterize the pharmacokinetic profile of repeated doses of ACT-01 in subjects with AON ;Primary end point(s): Assessment of the primary endpoint will be carried through : Safety parameters: Incidence of adverse events at month 6 in ACT-01-treated subjects versus placebo treated subjects ;Timepoint(s) of evaluation of this end point: Month 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main secondary endpoints: • Change in ganglion cell and inner plexiform layer thickness in the affected eye measured with optical coherence tomography (OCT) at month 1, month 3, month 6 and month 12 compared to baseline in the affected eye • Change in Retinal Nerve Fibre Layer thickness in the affected eye measured with OCT at month 1, month 3, month 6 and month 12 compared to baseline in the affected eye Other secondary endpoints: • Change on the 2.5% ETDRS Low Contrast Letter Acuity chart and ETDRS high contrast visual acuity measured at M1, M3, M6 and M12 in the affected eye compared to baseline • Change of Humphrey Visual Field evaluations measured in the affected eye at month 1, month 3, month 6 and month 12 compared to baseline • Change of latency and amplitude of Visual Evoked Potential at month 3, month 6 and month 12 compared to baseline • Change of Expanded Disability Status Scale at month 1, month 3, month 6 and month 12 compared to baseline • Rate of treatment switch at 12 months for subjects receiving Disease modifying therapy for multiple sclerosis • Safety parameters: Incidence of adverse events at M12 in ACT-01-treated subjects versus placebo • Pharmacokinetics parameters: Individual and mean plasma ACT-01 concentration time data at t1 (first day of treatment): 0 (pre-dose) and 0.5 h, 1h, 1.5h, 2h, 3h and 4h post start of the infusion; t2-t5: 0 (pre-dose); with Cmax (Maximum concentration), Tmax (time to maximum observed concentration, AUC0-t (Area under the concentration time curve (AUC) from the time of dosing to the time of the last measurable concentration) ;Timepoint(s) of evaluation of this end point: Month 6 | — |
Countries
France
Contacts
Public ContactLucia Septien
ACCURE TX FRANCE SASU
Outcome results
None listed