Study of NG01 Cell Therapy in Secondary Progressive Multiple Sclerosis

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Secondary Progressive Multiple Sclerosis (SPMS)
• Intervention / Treatment: Biological: NG01 - Autologous bone marrow derived human stromal cells; Other: Sodium Chloride 0.9%

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).

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Flavia Nelson, MD; Phone Number: 305-243-4015; Email: fxn133@med.miami.edu

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah University Hospital
    • Contact: Panayiota Petrou, MD; Phone Number: 972-2-6776639; Email: petroupanayiota@gmail.com
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital & Clinics - Sylvester Comprehensive Cancer Center - Neurology
      • Principal Investigator: Flavia Nelson, MD
      • Contact: Flavia Nelson, MD; Phone Number: 305-243-4015; Email: fxn133@med.miami.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants aged 18 to 65 years old.
2. Diagnosis of SPMS.
3. 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.
4. EDSS at the screening visit from 3.5 to 6.5 at screening.
5. T25FW at the screening visit of from 8.0 to 25 seconds.

Exclusion Criteria:

1. Documented clinical relapse during the 24 months prior to enrollment and/or evidence of enhancing lesions on an MRI obtained at screening.
2. Pregnancy, breast feeding or women with childbearing potential without an acceptable form of contraception.
3. History of a general chronic handicapping/incapacitating disease other than MS.
4. Participants with clotting disorders
5. Participants unable to undergo an MRI scan.
6. Participants with uncontrolled hepatic disorders, renal or cardiovascular disease, or cancer.
7. Laboratory tests out of normal ranges considered by the investigator as clinically significant.
8. Participants with history or current alcohol abuse or drug addiction.
9. Untreated or uncontrolled psychiatric disorders, or positive suicidal risk assessed by Columbia-Suicide Severity Rating Scale (C-SSRS).
10. 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.
11. Participants who have ever received NG01/MSCs treatment.
12. 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.
13. Relapse occurring between screening and randomization.
14. Less than 6 months of the current disease-modifying therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100x10^6 cells; 15 participants with SPMS will receive 4 IT administrations of NG01 (100×10^6 cells), 3 months apart	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.
Experimental: 50x10^6 cells; 15 participants with SPMS will receive 4 IT administrations of NG01 (50×10^6 cells), 3 months apart	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.
Placebo Comparator: Placebo; 15 participants with SPMS will receive 4 IT administrations of placebo solution, 3 months apart	Other: Sodium Chloride 0.9%; The placebo for use in the NG01 clinical trial is 0.9% Sodium Chloride Solution for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Ability	Proportion of participants who achieved improvement in walking ability over baseline by mean change in walking speed based on the Timed 25-Foot Walk (T25FW) test, averaged over visits at month-6, month-9 and month-12. Baseline is defined as the change in average timed walk compared to baseline (average timed walk at 6-, 9-, 12-months minus baseline < 0)	12 months
Incidence of Treatment-Emergent Adverse Events (AEs)	The occurrence of treatment-related AEs will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 following enrollment, NG01 or placebo administrations (intrathecal), and during the 6 months of follow-up.	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Speed	The change in walking speed will be assessed based on the average of two separate T25FW tests obtained during each study visit. The proportion of responders with 10, 15 or 20% improvement in walking speed will be assessed based on the average of two separate T25FW tests obtained during each study visit.	12 months
Neuroimaging Parameters - Change in T2-hyperintense Lesion	Change in T2-hyperintense lesion number and volume will be assessed by 3 tesla (3T) brain Magnetic Resonance Imaging (MRI) using automated volumetric analysis.	12 months
Neuroimaging Parameters - Change in T1-hypointense Lesion	Change in T1-hypointense lesion volume will be assessed by 3 tesla (3T) brain MRI using automated volumetric analysis.	12 months
Neuroimaging Parameters - Change in Brain and Thalamus	Change in whole brain and thalamic volume will be assessed by 3 tesla (3T) brain MRI using automated volumetric analysis	12 months
Efficacy - Finger Dexterity	Finger dexterity will be assessed by the 9-hole peg test (9HPT)	12 months
Quality of Life (QoL)	Quality of Life (QoL) will be assessed by 12-Item Short Form Survey (SF-12). Patients fill out a 12-question survey which is then scored by a clinician or researcher. The survey includes the following domains: Limitations in physical activities because of health problems.; Limitations in social activities because of physical or emotional problems; Limitations in usual role activities because of physical health problems; Bodily pain; General mental health (psychological distress and well-being); Limitations in usual role activities because of emotional problems; Vitality (energy and fatigue); General health perceptions	12 months
Fatigue	Level of fatigue will be assessed by Modified Fatigue Impact Scale (MIFS-21). The scores are 0 (Never), 1(Rarely), 2 (Sometimes), 3 (Often), 4 (Almost always). Physical Subscale can range from 0 to 36. Cognitive Subscale can range from 0 to 40. Psychosocial Subscale can range from 0 to 8. The subscale scores are computed by adding raw scores on specific questions, in accordance with questionnaire instructions. Total MFIS Score can range from 0 to 84. It is computed by adding scores on the physical, cognitive, and psychosocial subscales.	12 months
Walking ability	Walking will be assessed by 12-item Multiple Sclerosis Walking Scale (MSWS-12). The original scoring provides options 1-5 for each item, with 1 meaning no limitation and 5 meaning extreme limitation on the gait-related item. In a version 2, three items are scored 1-3, and nine items are scored 1-5.	12 months
Efficacy - Congnition	Cognitive assessment will be done using the Symbol Digit Modalities Test (SDMT)	12 months
Change in Disability	Proportion of participants with no increase in month-3 confirmed disability worsening (CDW) will be assessed by Expanded Disability Status Scale (EDSS). The EDSS ranges from 0 to 10. Scores are in half unit steps - 3, 3.5, 4 and so on. The greater the level of disability, the higher the score out of ten.	12 months

Collaborators and Investigators

• Sponsor: NeuroGenesis Ltd.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 21, 2025
• First Submitted That Met QC Criteria: April 28, 2025
• First Posted (Actual): May 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Autologous cell therapy; Secondary progressive multiple sclerosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neoplastic Processes; Multiple Sclerosis; Sclerosis; Neoplasm Metastasis; Multiple Sclerosis, Chronic Progressive
• Other Study ID Numbers: NG01-P2b-SPMS-US

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No