- Randomized, two-arm, double-blind placebo-controlled study in 36 acute optic neuritis (AON) patients, to be monitored over 6- and 12-month period
- Evaluation of safety, tolerability and efficacy of ACT-01 versus placebo on retinal layers’ thickness and clinical vision parameters
BARCELONA, Spain I March 1, 2021 I Accure Therapeutics, a private translational R&D engine at clinical stage in the Central Nervous System (CNS) field, today announces it has enrolled the first patient in its ACUITY phase II clinical trial – in patients with acute optic neuritis (AON). A total of 36 patients will be enroled in two randomized parallel groups. They will be followed for six months to measure and assess safety and preliminary signs of efficacy. Results are expected in the second half of 2022.
The ACUITY study is carried out within the neurology-opthalmology network of the Public University Hospital Group in Paris (APHP), with the leading site at La Pitié-Salpétrière hospital. The study is under the supervision of lead investigator Dr. Céline Louapre, from the Paris Brain Institute (Institut du Cerveau et de la Moelle épinière, ICM), and scientific advisor Dr. Sophie Bonnin, from the Department of Ophthalmology at La Pitié-Salpétrière. ICM, located at La Pitié-Salpetrière, brings patients, doctors and researchers together, with the aim of rapidly developing treatments for disorders of the nervous system and enabling patients to benefit from them as quickly as possible.
“This study is set to confirm the safety and tolerability of Accure’s candidate and to provide preliminary proof-of-efficacy – both as clinical and imaging evidenced by optical coherence tomography (OCT) – of ACT-01 in patients living with inflammatory demyelinating diseases such as acute optic neuritis,” said Dr. Celine Louapre. “These first efficacy results in patients will give us an estimate of the treatment effect and help us calculate the adequate sample size for the next clinical study.”
A total of 36 eligible subjects will be randomized within ten days of the onset of AON (visual loss symptoms) to receive five intravenous infusions of ACT-01 (N=18) or placebo (N=18), over a five-day period. As is the standard of care for AON, all patients will receive intravenous corticosteroid as concomitant therapy – unless contra-indicated. Patients will be assessed by a neurologist and an ophthalmologist; clinically and with non-invasive routine imaging tests.
Preliminary efficacy of ACT-01 will be assessed over a six month period – post onset of AON symptoms. By this time, almost all subjects are expected to have come to the end of their natural recovery; therefore this strategic timeline is used to compare the profiles of disease progression, and structural and functional outcomes between subjects in each treatment arm. For the majority of patients, thinning of the retinal layers in the affected eye occurs within the first six months of the onset of AON, as measured by the RNFL- retinal nerve fiber layer and the GCIPL – ganglion cell-inner plexiform layer, in an OCT scan.
“We are very excited to initiate this phase II study with our lead candidate ACT-01 in patients with acute inflammatory-demyelinating disorders,” said Dr. Rossella Medori, CMO at Accure Therapeutics. “The results from the phase II study have the potential to serve as a solid foundation for expanding future pivotal clinical development of our first-in-class disease modifying drug candidate, to address the challenges of residual and accrued disability in other chronic neurodegenerative CNS disorders.”
Join our webinar on Tuesday March 2, at 7:30pm CET/1:30pm ET/10:30am PST and listen to expert speakers Prof. Shiv Saidha, Johns Hopkins University (Baltimore, US) and Prof. Fiona Costello, University of Calgary (Canada), as they discuss Acute Optic Neuritis. They will be covering the following:
- Acute Optic Neuritis (AON) is most often a prodrome (CIS) or a relapse during the course of MS
- AON is an excellent clinical development path into MS for neuroprotection
- Discussions of recent trials conducted in patients with Acute Optic Neuritis
- There will be an opportunity for a Q&A session after the webinar presentation
To register and confirm your interest:Zoom registration URL
The following criteria apply to patient recruitment:
- Inclusion of patients aged between 18-60 years diagnosed with unilateral AON with a demyelinating origin (with or without diagnosis of multiple sclerosis) with an onset of visual loss symptoms in the ten days previous to randomization, with an expanded disability status scale score (EDSS) between 0 and 5.5
- Major exclusion: optic neuropathy of non-demyelinating origin, e.g. infectious diseases, ischemic, trauma, tumor or other, and known neuromyelitis optica with autoantibodies against aquaporin-4 (AQP4-Abs)
More information on the trial
About ACT-01
- ACT-01 is a peptidomimetic first-in-class disease-modifying treatment for multiple sclerosis (MS) and acute optic neuritis, the latter with orphan drug designation by the US FDA and the EMA in the EU. It crosses the blood-brain barrier by active transport, to promote neuronal cell survival and myelination
- In the cell, ACT-01 activates the downstream steps of BDNF and IGF-1 neurotrophic factor pathways, and binds selectively to a small group of kinases. ACT-01 promotes translocation out of the nucleus of the transcription factor FOXO-3, highly expressed in the central nervous system. FOXO-3’s translocation inhibits expression of pro-apoptotic genes and induces the expression of anti-apoptotic genes, antioxidant enzymes and differentiation pathways
- In vivo, ACT-01 demonstrated neuroprotective properties by reducing damage to the optic nerve and retina in animal models of AON and high-pressure glaucoma. ACT-01 also decreased paralysis progression in the reference experimental autoimmune encephalomyelites (EAE) animal model for MS
- A phase I study showed the safety and tolerability of single and multiple doses of intravenous ACT-01 in healthy volunteers. Collective data from these studies show therapeutic potential for ACT-01 in the treatment of neurodegenerative diseases, such as AON and MS
About acute optic neuritis (AON)
AON is an acute inflammatory demyelinating disorder of the optic nerve. The affected patients present with unilateral, subacute and painful visual loss. AON is considered a rare disease; with an incidence of one to five cases per 100,000 people per year.
While in up to 20% of subjects, AON can be the initial presenting symptom of multiple sclerosis (MS), in half the cases, AON occurs as an MS relapse during the course of the disease.
There is wide variability in symptom severity and recovery, without predictors for poor recovery with residual dysfunction. It is reported that severity and recovery from the initial relapse are associated with severity and recovery for subsequent recurrences.
Acute corticosteroids are the usual standard of care, but currently, there is no approved therapy that preserves vision or the integrity of ganglion/retinal nerve fibres after an episode of AON. A neuroprotective drug is therefore needed; one that could prevent long-term axonal loss and hopefully lead to a better visual outcome.
About Accure Therapeutics
Accure Therapeutics is a private translational R&D engine at clinical stage in the Central Nervous System (CNS) field. Based in Barcelona (Spain), it was launched in 2020 with a Series A funding led by Alta Life Sciences Spain I and supported by the Centre for Technological and Industrial Development (CDTI). This European company with an international mindset boasts a unique portfolio of three new chemical entity programs pursuing innovative targets – with potential to accommodate others. Accure aims to develop new disease modifying drugs to treat serious conditions such as optic neuritis, multiple sclerosis, Parkinson’s disease and epilepsy. With an experienced business and scientific team, Accure Therapeutics is one of the few companies that operate in an agnostic fashion on initial science to deliver cutting-edge drugs in CNS.
https://accure.health/
SOURCE: Accure Therapeutics
