Study of NG01 Cell Therapy in Secondary Progressive Multiple Sclerosis

This is a multi-center, international Phase 2b, dose finding, randomized, double-blinded, placebo-controlled, three arm study, designed to assess the safety and efficacy of 4 IT administrations of NG01, compared to placebo, with a 4-month run-in period followed by a period of 9 months treatment with 6 months of follow-up, in patients with SPMS. Participants will continue to receive their customary MS treatment regimen at a stable dose.

The study will enroll 45 participants with secondary progressive multiple sclerosis (SPMS), randomized in a 1:1:1 ratio, to receive four intrathecal administrations-3 months apart over a 9-month period-of either high-dose NG01, low-dose NG01, or placebo. All participants will undergo clinical and safety assessments throughout the 9-month treatment period.

Upon completion of the 9-month treatment period, double-blind treatment and assessment period, participants will be followed clinically for an additional 6 months. The primary clinical outcome assessment and magnetic resonance imaging (MRI) acquisition for imaging assessments will occur post-treatment initiation (baseline).

Inclusion criteria

• Participants aged 18 to 65 years old.
• Diagnosis of SPMS.
• Documented EDSS worsening over the 2 years prior to study entry of ≥1 point for participants with EDSS <6.0 at screening, and ≥0.5 point for participants with EDSS ≥6.0 at screening, or a documented worsening of at least 20% in the T25FW. If documented T25fW or EDSS is not available, a written summary of the clinical evidence of disability worsening over the previous 2 years and retrospective assessment of EDSS score from data up to 2 years prior to screening, must be submitted for central review by adjudication committee.
• EDSS at the screening visit from 3.5 to 6.5 at screening.
• T25FW at the screening visit of from 8.0 to 25 seconds.

Exclusion criteria

• Documented clinical relapse during the 24 months prior to enrollment and/or evidence of enhancing lesions on an MRI obtained at screening.
• Pregnancy, breast feeding or women with childbearing potential without an acceptable form of contraception.
• History of a general chronic handicapping/incapacitating disease other than MS.
• Participants with clotting disorders
• Participants unable to undergo an MRI scan.
• Participants with uncontrolled hepatic disorders, renal or cardiovascular disease, or cancer.
• Laboratory tests out of normal ranges considered by the investigator as clinically significant.
• Participants with history or current alcohol abuse or drug addiction.
• Untreated or uncontrolled psychiatric disorders, or positive suicidal risk assessed by Columbia-Suicide Severity Rating Scale (C-SSRS).
• Participation in another research study involving an investigational product (IP) in the 90 days prior to inclusion, or planned use of another IP during the study duration.
• Participants who have ever received NG01/MSCs treatment.
• Participants who, in the opinion of the investigator, are unable to fully comprehend the consenting process or likely to be non-compliant with the study procedures or for whom long-term follow-up seems difficult to achieve.
• Relapse occurring between screening and randomization.
• Less than 6 months of the current disease-modifying therapy