Clinical trial NCT06365216: ALS Phase II Study of NX210c
Official title: A Double-blind, Randomized, Placebo-controlled, Multicentric, Phase II Study in Adult Patients With Amyotrophic Lateral Sclerosis (ALS) to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Multiple Intravenous Infusions of NX210c
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lead sponsor: Axoltis Pharma
Sponsor class: INDUSTRY
Collaborators: name: ACT4ALS network
First posted: 2024-04-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo-controlled, multicentric, phase II study in adult patients with ALS to assess efficacy, safety, tolerability and pharmacokinetics of multiple intravenous infusions of NX210c.

Two doses of NX210c (5 mg/kg and 10 mg/Kg) will be investigated, along with a placebo group which will serve as a reference. Patients will be randomized to one of 3 arms in an allocation ratio of 3:3:2.

Patients will participate up to approximately 20 weeks: up to 30 days for screening, 26 days of treatment and 3 months of follow-up. Lumbar punctures will assess cerebrospinal fluid (CSF) NfL and other key CSF biomarkers related to ALS and drug mechanism of action. Blood sampling will be drawn for safety, PK and biomarkers testing. Urine will equally be collected for biomarkers. A comprehensive assessment of the disease, including the ALS Functional Rating Scale (ALSFRS-R) will be performed.
Primary purpose: TREATMENT

Brief summary: This study will investigate the efficacy, safety, tolerability and pharmacokinetics (PK) of multiple intravenous infusions of NX210c, at two dose levels, in patients with Amyotrophic lateral sclerosis (ALS).

Detailed description: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that predominantly affects motor neurons of both the brain and the spinal cord. This leads to muscular atrophy and paralysis, with the majority of patients succumbing to respiratory failure 3-4 years from symptom onset. To date, therapeutic options for ALS are limited and there is no curative treatment. Management of ALS is otherwise supportive and palliative.

There is strong evidence for blood-brain and blood-spinal cord barrier dysfunction in the early stages of ALS. Preclinical in vitro and in vivo data have shown that NX210c exhibits important properties that may be suitable for the treatment of neurological disorders in humans i.e., blood-brain barrier (BBB) integrity restoration, neurotransmission enhancement and neuroprotection.

Based on the safety data collected in a first-in-human single ascending dose study and a multiple ascending dose (MAD) study in healthy elderly subjects, NX210c has been demonstrated to be well tolerated and without safety concerns.

Eligibility criteria: Inclusion Criteria:

* Aged ≥ 18 years, inclusive at screening.
* Patients diagnosed as having possible, probable, probable laboratory-supported, or definite ALS according to El Escorial Revised criteria.
* King's Clinical Staging Stage ≤3, disease duration of ≤ 36 calendar months

Exclusion Criteria:

* Patients with any cognitive or psychological disorder, intellectual disability or other significant impairment that would result in an inability to understand and sign the informed consent.
* History of any clinically significant or unstable medical, neurological, psychiatric condition, disorder or disease (other than ALS) or social circumstances that, based on the investigator's judgment, would interfere with the conduct of the study or pose a risk to the patient if they were to participate.

Primary outcomes:
measure: The effect of NX210c on blood neurofilament light chain (NfL) or on a blood and cerebrospinal fluid (CSF) biomarker of BBB integrity.
timeFrame: From predose to 6-week follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire De Bordeaux
city: Bron
country: France
facility: CHU de Lyon HCL
city: Clermont-Ferrand Cedex 1
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand - Hôpital Gabriel Montpied
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Limoges Cedex 1
country: France
facility: Centre Hospitalier Et Universitaire de Limoges
city: Montpellier Cedex 5
country: France
facility: Centre Hospitalier Universitaire de Montpellier
city: Nantes Cedex 01
country: France
facility: Centre Hospitalier Universitaire de Nantes - Hôpital Nord Laennec
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: Hôpital de la Pitié Salpêtrière
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: Tours Cedex 9
country: France
facility: Centre Hospitalier Regional Universitaire de Tours
Study officials:
References: