Study of NG01 Cell Therapy in Secondary Progressive Multiple Sclerosis

Official title

A Double Blind, Randomized, Placebo Controlled Phase 2b Study to Evaluate the Safety and Clinical Efficacy of Treatment With the Autologous Cell Therapy Product, NG01, in Patients With Secondary Progressive Multiple Sclerosis

Overview

The goal of this clinical trial is to assess the safety and efficacy of repeated intrathecal (IT) injection of NG01, autologous bone marrow derived human stromal cells, in treating Secondary Progressive Multiple Sclerosis (SPMS), compared to placebo. The study will assess the proportion of participants demonstrating improvement in walking ability, defined as a reduction in the average time to complete the Timed 25-Foot Walk (T25FW) at 6, 9, and 12 months compared to baseline. This will be analyzed by the mean change in walking speed across these time points. The study will also evaluate the incidence and nature of treatment-emergent adverse events (AEs). Participants will receive intrathecal administrations of NG01, by lumbar puncture, and will be followed up for 6 months after their fourth administration.

Detailed description

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).

Interventions

• Biological NG01 - Autologous bone marrow derived human stromal cells
  NG01 is a cellular therapy product of autologous stromal cells derived from the bone marrow of multiple sclerosis (MS) patients. NG01 is provided as a cell suspension for intrathecal injection.
• Other Sodium Chloride 0.9%
  The placebo for use in the NG01 clinical trial is 0.9% Sodium Chloride Solution for Injection

Primary outcome measures

• Walking Ability [Time frame: 12 months]
• Incidence of Treatment-Emergent Adverse Events (AEs) [Time frame: 15 months]

Secondary outcome measures (10)

• Walking Speed [Time frame: 12 months]
• Neuroimaging Parameters - Change in T2-hyperintense Lesion [Time frame: 12 months]
• Neuroimaging Parameters - Change in T1-hypointense Lesion [Time frame: 12 months]
• Neuroimaging Parameters - Change in Brain and Thalamus [Time frame: 12 months]
• Efficacy - Finger Dexterity [Time frame: 12 months]
• Quality of Life (QoL) [Time frame: 12 months]
• Fatigue [Time frame: 12 months]
• Walking ability [Time frame: 12 months]
• Efficacy - Congnition [Time frame: 12 months]
• Change in Disability [Time frame: 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center - Neurology — Miami

Israel · 1 center

• Hadassah University Hospital — Jerusalem

Publications

• Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321. PMID 26751635
• Petrou P, Kassis I, Ginzberg A, Halimi M, Yaghmour N, Abramsky O, Karussis D. Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis. Front Neurol. 2021 May 31;12:639315. doi: 10.3389/fneur.2021.639315. eCollection 2021. PMID 34135843
• Petrou P, Kassis I, Levin N, Paul F, Backner Y, Benoliel T, Oertel FC, Scheel M, Hallimi M, Yaghmour N, Hur TB, Ginzberg A, Levy Y, Abramsky O, Karussis D. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020 Dec 1;143(12):3574-3588. doi: 10.1093/brain/awaa333. PMID 33253391
• Petrou P, Kassis I, Yaghmour NE, Ginzberg A, Karussis D. A phase II clinical trial with repeated intrathecal injections of autologous mesenchymal stem cells in patients with amyotrophic lateral sclerosis. Front Biosci (Landmark Ed). 2021 Oct 30;26(10):693-706. doi: 10.52586/4980. PMID 34719198

Identifiers

NCT: NCT06961383 · NG01-P2b-SPMS-US

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗