H-L-TRYPHOPHANYL-L-SERYL-GLYCYL-L-TRYPTOPHANYL-L-SERYL-L-SERYL-L-CYSTEINYL-L-SERYL-L-ARGINYL-L-SERYL-L-CYSTEINYL-GLYCYL-OH (DISULFIDE BOND), ACETATE SALT for Amyotrophic lateral sclerosis (ALS)

Inclusion criteria

• {"criterion_text":"- Patient able to provide informed consent, geographically accessible to the site and able and willing to comply with all study requirements of the protocol, including two lumbar punctures.\n- Patients diagnosed as having possible, probable, probable laboratory-supported, or definite ALS, either sporadic or familial, according to El Escorial Revised criteria.\n- Disease duration of ≤ 36 calendar months (i.e., ALS symptom onset to the baseline timepoint) at baseline.\n- King’s Clinical Staging Stage ≤3 at baseline.\n- Any NfL value available before screening should be compatible with the diagnosis of ALS (>10 pg/mL). No NfL value known before screening does not exclude the patient.\n- Serum NfL study value available at baseline.\n- SVC ≥ 55% predicted value as adjusted for gender, height, and age at baseline.\n- Patients who are being treated with riluzole or symptomatic treatment for ALS (including over the counter medication or supplements) must have been on a stable dose for at least 30 days before baseline. Riluzole-naïve patients or having stopped riluzole at least 2 weeks prior to screening are permitted in the study.\n- For the extension follow-up only: the patient must be able to provide informed consent, have participated to the SEALS study and have received at least 50% of the treatment doses.\n- Satisfactory peripheral venous access; no central catheterization will be permitted.\n- Satisfactory CSF volume at screening (i.e., 1.5 mL minimum).\n- Maximum body weight ≤110 kg at baseline.\n- For female patients: not pregnant and have a negative pregnancy blood test (women of childbearing potential [WOCBP] only) at screening and baseline.\n- For female patients: must not be breastfeeding, have no intention of becoming pregnant during the study, and use acceptable methods of contraception or abstain from intercourse. WOCBP must agree to use highly effective contraception consisting of two forms of birth control, one of which must be a male barrier method such as a latex or polyurethane condom from the start of dosing throughout the clinical study period, and for 90 days after the final administration of study treatment. Women of non-childbearing potential (WONCBP) will be considered those who are sterilized or post-menopausal. A sterilized patient will have either undergone surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy; participant reported information) at least 90 days prior to baseline; postmenopausal patients will have been amenorrheic for > 12 consecutive months before screening and FSH levels > 30 IU/L. Essure® fallopian tube coil placement is not accepted as surgical sterilization because of the high failure rate.\n- Male patients must either declare and confirm abstinence or must be willing and able to use effective contraception. Male patients engaging in sexual intercourse with WOCBP, both the male patient and his female partner must use highly effective contraception consisting of 2 forms of birth control, one of which must be a male barrier method such as a latex or polyurethane condom from the start of dosing throughout the clinical study period, and for 90 days after the final administration of study treatment. Males who have had a vasectomy must have a confirmed zero sperm count or must agree after receiving the first dose of study drug either to use acceptable methods of contraception or abstain from intercourse.\n- For male patients: The patient must not donate sperm at any time from the start of dosing, throughout the clinical study period, and for 90 days after the final administration of study treatment.\n- Male or female, 18 years of age or older at the time of signing the ICF."}

Exclusion criteria

• {"criterion_text":"- 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.\n- Any contra-indication to glucose 5% and/or any hypersensitivity to any component of the IMP formulation.\n- Any known significant brain or spinal disease that would interfere with the lumbar puncture process, CSF circulation or safety assessment.\n- Any person who is an employee of the study sponsor or stakeholder partners involved in the conduct of the study, or an immediate relative of an investigator or study staff.\n- Minors, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, adult patients under legal protection or unable to express consent.\n- Exposure to an investigational drug within 12 weeks prior to screening, or at least a period of 5 half-lives for the investigational drug, whichever is longer; for antisense therapy targeting SOD1, if the patient has completed treatment within 6 months of the screening visit. Any drug intended for ALS (other than riluzole and symptomatic treatment) will not be allowed, except during the extension follow-up period.\n- Patient with a history of any clinically significant or unstable medical (including hepatic and renal), neurological, psychiatric condition, disorder or disease (other than ALS) or social circumstances that, based on the investigator's judgment, would 1) interfere with the patient's ability to comply with the protocol and all study procedures or 2) compromise study integrity or 3) pose a risk to the patient if they were to participate (e.g., previous acute coronary syndrome within 3 months of screening, major surgery within 2 months of screening) or physical examination, uncontrolled hypertension (blood pressure > 160/100 mm Hg), at screening or baseline.\n- History of malignancy within 3 years of screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 6 months may be eligible, based on the investigator’s judgement.\n- Any clinically significant abnormalities in screening laboratories, including hepatic and renal impairment (e.g., aspartate aminotransferase (AST) >3× upper limit of normal (ULN); alanine aminotransferase (ALT) >3 × ULN; total bilirubin >2 × ULN; serum creatinine >2.0 × ULN). Retesting may be performed, on discussion with the medical monitor.\n- Patient under anticoagulant treatment that cannot be held or stopped without putting at risk the patient’s life.\n- Positive test to human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus or hepatitis B virus.\n- Patients with active infections or, based on the investigator’s judgement, any active/uncontrolled inflammatory condition(s)."}

Primary endpoints

• {"endpoint_text":"- Changes in serum NfL from predose to 6-week follow-up OR Changes in Albumin CSF/serum quotient (Qalb) from predose to 6-week follow-up.","definition_or_measurement_approach":"Change from predose to 6-week follow-up in (a) serum neurofilament light chain (NfL) and/or (b) CSF/serum albumin quotient (Qalb); measured by biomarker assays on blood and CSF at predose and at 6-week follow-up."}

Secondary endpoints

• {"endpoint_text":"- Changes in serum NfL from predose to 4-month follow-up or intervals from predose to 4-month follow-up.","definition_or_measurement_approach":"Changes in serum NfL measured at predose and at 4-month follow-up (or interval timepoints up to 4 months)."}
• {"endpoint_text":"- Changes in CSF NfL from predose to 6-week follow-up.","definition_or_measurement_approach":"Change in cerebrospinal fluid (CSF) NfL from predose to 6-week follow-up measured on CSF samples."}
• {"endpoint_text":"- Changes in secondary blood biomarkers from predose to 6-week or 4-month follow-up or intervals from predose to 4-month follow-up.","definition_or_measurement_approach":"Measurement of prespecified secondary blood biomarkers at predose and at 6-week and/or 4-month follow-up (or interval timepoints)."}
• {"endpoint_text":"- Changes in secondary urine biomarkers from predose to 6-week or 4-month follow-up or intervals from predose to 4-month follow-up.","definition_or_measurement_approach":"Measurement of prespecified urine biomarkers at predose and at 6-week and/or 4-month follow-up (or interval timepoints)."}
• {"endpoint_text":"- Changes in secondary CSF biomarkers from predose to 6-week follow-up.","definition_or_measurement_approach":"Measurement of prespecified CSF biomarkers at predose and at 6-week follow-up."}
• {"endpoint_text":"- Changes in Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R, subscores and total) from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Change in ALSFRS-R subscores and total score from baseline to 4 months (or interval timepoints)."}
• {"endpoint_text":"- Changes in Slow Vital Capacity (SVC) from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Change in slow vital capacity (SVC) measured at baseline and at 4 months (or interval timepoints)."}
• {"endpoint_text":"- Changes in hand-held dynamometry (HHD) muscles and bilateral hand grip from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Change in muscle strength measured by hand-held dynamometry and bilateral handgrip from baseline to 4 months (or interval timepoints)."}
• {"endpoint_text":"- Evaluate disease progression rate: Delta FS (ΔFS) from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Delta FS (ΔFS) calculated from baseline to 4 months (or interval timepoints) to assess disease progression rate."}
• {"endpoint_text":"- Evaluation of time from baseline to the occurrence of either death, or tracheotomy or permanent assisted ventilation (>22 hours daily for >7 consecutive days, hospitalization), or decrease in weight, whichever comes first.","definition_or_measurement_approach":"Time-to-event analysis from baseline to the first occurrence of listed events (death, tracheotomy/permanent assisted ventilation, or weight decrease)."}
• {"endpoint_text":"- Recorded time from baseline to death.","definition_or_measurement_approach":"Survival time measured from baseline to date of death."}
• {"endpoint_text":"- Changes in CAFS from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Change in Combined Assessment of Function and Survival (CAFS) from baseline to 4 months (or interval timepoints)."}
• {"endpoint_text":"- Change in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) from baseline to 4-month follow-up or intervals from baseline to 4-month follow-up.","definition_or_measurement_approach":"Change in ALSAQ-40 score from baseline to 4 months (or interval timepoints)."}
• {"endpoint_text":"- Secondary safety and tolerability endpoints: Incidence of discontinued treatment due to a treatment-emergent adverse event (TEAE), Incidence of dose decision required during the treatment period due to TEAE, Incidence of discontinued patient due to local tolerability issue(s), Incidence of dose decision required during the treatment period due to local tolerability issue.","definition_or_measurement_approach":"Safety/tolerability endpoints measured by incidence counts of TEAEs leading to discontinuation, dose decisions, local tolerability issues during treatment period."}
• {"endpoint_text":"- Number of serious adverse events (SAEs), nature, incidence, and severity of TEAEs: Incidence of abnormal vital signs, Incidence of abnormal 12-lead electrocardiogram (ECG) assessments, Incidence of abnormal laboratory tests (hematology, biochemistry, urinalysis).","definition_or_measurement_approach":"Safety monitoring by recording SAEs, TEAEs, abnormal vital signs, ECGs, and laboratory tests (hematology, biochemistry, urinalysis)."}
• {"endpoint_text":"- Changes in physical and neurological examination.","definition_or_measurement_approach":"Changes from baseline in physical and neurological exam findings."}
• {"endpoint_text":"- Assessment of NX210c plasma PK parameters: Cmax, Tmax, AUC0-last, AUC0-inf, T1/2, CL, Vz on a subset of patients.","definition_or_measurement_approach":"Pharmacokinetic analysis of plasma NX210c on a subset: determination of Cmax, Tmax, AUC0-last, AUC0-inf, T1/2, clearance (CL), and volume of distribution (Vz)."}

France

Earliest CTIS Part Ii Submission Date

07-03-2024

Latest Decision Or Authorization Date

06-11-2025

Processing Time Days

609

Number Of Sites

16

Number Of Participants

80

Primary sponsor

Full Name

Axoltis Pharma

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Nuvisan France S.A.R.L.

Responsibilities

sponsorDuties codes: 14

Name

QPS Netherlands B.V.

Responsibilities

sponsorDuties codes: 15; value: Active biomarkers - Biomarker analysis

Name

Keyrus Life Science / Keyrus

Responsibilities

data/biomarker and RA activities (sponsorDuties codes: 10,11,3,5,6,7)

Name

Vigipharm

Responsibilities

sponsorDuties codes: 8

Name

RLM Consulting

Responsibilities

sponsorDuties codes: 12,15; values: CT admin of CTIS, Regulatory affairs Project Management

Third parties

• {"country":"France","full_name":"Nuvisan France S.A.R.L.","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"sponsorDuties codes: 15; value: Active biomarkers - Biomarker analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Keyrus Life Science","duties_or_roles":"sponsorDuties codes: 10,11,3,5,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Vigipharm","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Keyrus","duties_or_roles":"sponsorDuties codes: 10,11,3,5,6,7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"RLM Consulting","duties_or_roles":"sponsorDuties codes: 12,15; values: CT admin of CTIS, Regulatory affairs Project Management","organisation_type":"Pharmaceutical company"}