Amyotrophic Lateral Sclerosis (ALS)Phase 3NCT03280056

Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients

A Phase 3 study testing NurOwn® (MSC-NTF cells) and Bone Marrow aspiration in people with Amyotrophic Lateral Sclerosis (ALS), run by Brainstorm-Cell Therapeutics at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will evaluate the safety and efficacy of repeated administration of NurOwn® (MSC-NTF cells) therapy, which is based on transplantation of autologous bone marrow derived mesenchymal stromal cells (MSC), which are enriched from the patient's own bone marrow, propagated ex vivo and induced to secrete… Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Amyotrophic Lateral Sclerosis (ALS)
What is being tested?: NurOwn® (MSC-NTF cells) and Bone Marrow aspiration
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 196 participants
Where: 6 sitesUnited States
Study dates: 28 Aug 2017to 29 Sep 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
Having onset of ALS disease symptoms, including limb weakness within 24 months at the Screening Visit.
ALSFRS-R ≥ 25 at the screening Visit.
Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and age at the screening Visit.
Rapid progressors
Participants taking a stable dose of Riluzole are permitted in the study
Citizen or permanent resident of the United States or Canadian citizen able to travel to a US site for all follow-up study visits

Who cannot join

Prior stem cell therapy of any kind
History of autoimmune or other serious disease (including malignancy and immune deficiency) that may confound study results
Current use of immunosuppressant medication or anticoagulants (per Investigator discretion)
Exposure to any other experimental agent or participation in an ALS clinical trial within 30 days prior to Screening Visit
Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use edaravone at any time during the course of the study including the follow up period
Use of non-invasive ventilation (BIPAP), diaphragm pacing system or invasive ventilation (tracheostomy)
Feeding tube
Pregnant women or women currently breastfeeding

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Massachusetts General Hospital
Boston, Massachusetts, 02115
University of California Irvine Alpha Stem Cell Clinic
Irvine, California, 92697
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Mayo Clinic
Rochester, Minnesota, 55905
California Pacific Medical Center
San Francisco, California, 94115
University of Massachusetts Medical School
Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Phase 3, Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Participants With ALS

The autologous NurOwn® (MSC-NTF cells) are back-transplanted into the patient intrathecally by standard lumbar puncture where neurons and glial cells are expected to take up the neurotrophic factors secreted by the transplanted cells

Read the detailed description

Neurotrophic factors (NTFs) are potent survival factors for embryonic, neonatal, and adult neurons and are considered potential therapeutic candidates for ALS. Delivery of multiple NTFs to the immediate environment of afflicted neurons in ALS patients is expected to improve their survival and thus slow down disease progression and alleviate symptoms. NTF-secreting mesenchymal stromal cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients.

Participants meeting the inclusion and exclusion criteria will be randomized and will undergo bone-marrow aspiration. MSC of the participants randomized to the treatment group will be induced into MSC-NTF cells. Participants will undergo a total of three intrathecal (IT) transplantations with NurOwn® (MSC-NTF cells) or matching placebo at three bi-monthly intervals

Conditions: Amyotrophic Lateral Sclerosis (ALS)
Being tested: NurOwn® (MSC-NTF cells), Placebo, Bone Marrow aspiration
Keywords: MSC, Autologous, Neurotrophic factors
Medical subject headings: Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NurOwn® (MSC-NTF cells)Biological
NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10^6 cells every 8 weeks
NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors
PlaceboOther
One course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks
Placebo: liquid solution in syringe for injection
Bone Marrow aspirationOther
Bone Marrow aspiration

Study groups in NCT03280056
Study group	Role	What they receive
NurOwn® (MSC-NTF cells)	Active comparator	Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals Receives: Biological: NurOwn® (MSC-NTF cells); Other: Bone Marrow aspiration
Placebo	Placebo comparator	Three Intrathecal administrations of Placebo at bi-monthly intervals Receives: Other: Placebo; Other: Bone Marrow aspiration

What is being measured

The primary outcome is the main question the study is designed to answer.

The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo
The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.
Measured: 28 weeks following the first intrathecal injection

Secondary outcomes (3)

Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo
The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.
Measured: 28 weeks following the first intrathecal injection
Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28
The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.
Measured: 28 weeks following the first intrathecal injection
NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks
The combined Assessment of Function and Survival (CAFS) is a composite endpoint based on (1) the change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) score and (2) time to death.
On the ALSFRS-R, 12 functions are rated on 5-point ordinal rating scales (from 0 to 4) with a total score range (minimum and maximum score) of 0-48 (sum of all 12 items). The higher the score the better functioning. For the survival endpoint, the longer time the better outcome.
A patient's CAFS score represents a patient's rank in the study based on comparing the patient's outcome for both the change in ALSFRS-R and the time to death to all other patients in the study in a pairwise fashion. The ranked scores range from 001 to 189 (the number of subjects in the mITT population) with larger rank score numbers associated with a better outcome. The reported values are the mean rank scores in each group for the composite endpoint.
Measured: 28 weeks following the first intrathecal injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 201729 Sep 2020

First posted12 Sep 2017
Study start28 Aug 2017
Primary completion29 Sep 2020
Study completion29 Sep 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 196 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03280056
Sponsor's protocol ID: BCT-002-US
Status last verified: Feb 2024
First submitted: 29 Aug 2017
Last updated: 29 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Amyotrophic Lateral Sclerosis (ALS) trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Participants With ALS
ClinicalTrials.gov ID: NCT03280056
Acronym / sponsor ID: BCT-002-US
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Keywords: MSC, Autologous, Neurotrophic factors
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 196 participants (actual)
Lead sponsor: Brainstorm-Cell TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: California Institute for Regenerative Medicine (CIRM)
Study start: 28 Aug 2017 (actual)
Primary completion: 29 Sep 2020 (actual)
Study completion: 29 Sep 2020 (actual)
First posted: 12 Sep 2017 (actual)
Results: Posted 29 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study

Arm	Type	Receives
NurOwn® (MSC-NTF cells)	Active comparator	Biological: NurOwn® (MSC-NTF cells), Other: Bone Marrow aspirationThree Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals
Placebo	Placebo comparator	Other: Placebo, Other: Bone Marrow aspirationThree Intrathecal administrations of Placebo at bi-monthly intervals

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
Having onset of ALS disease symptoms, including limb weakness within 24 months at the Screening Visit.
ALSFRS-R ≥ 25 at the screening Visit.
Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and age at the screening Visit.
Rapid progressors

Key exclusion criteria (8 listed)

Prior stem cell therapy of any kind
History of autoimmune or other serious disease (including malignancy and immune deficiency) that may confound study results
Current use of immunosuppressant medication or anticoagulants (per Investigator discretion)
Exposure to any other experimental agent or participation in an ALS clinical trial within 30 days prior to Screening Visit
Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use edaravone at any time during the course of the study including the follow up period

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NurOwn® (MSC-NTF cells)NurOwn® (MSC-NTF): One course of treatment that includes three separate intrathecal injections of 100-125 x 10^6 cells every 8 weeks NurOwn® (MSC-NTF): Autologous, bone marrow-derived, mesenchymal stem cells secreting neurotrophic factors	Biological	NurOwn® (MSC-NTF cells)
PlaceboOne course of treatment that includes three separate intrathecal injections of Placebo every 8 weeks Placebo: liquid solution in syringe for injection	Other	Placebo
Bone Marrow aspirationBone Marrow aspiration	Other	NurOwn® (MSC-NTF cells), Placebo

Primary outcome

The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo
Time frame: 28 weeks following the first intrathecal injection
The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.

3 secondary outcomes

Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo
Time frame: 28 weeks following the first intrathecal injection
Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28
Time frame: 28 weeks following the first intrathecal injection
NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks
Time frame: 28 weeks following the first intrathecal injection

Results and safety

Results posted to the registry on 29 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NurOwn® (MSC-NTF Cells)	95	71
Placebo	94	73

Primary outcome: The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo

Time frame: 28 weeks following the first intrathecal injection. Count of participants. Unit: Participants

Measure	NurOwn® (MSC-NTF Cells) n = 95	Placebo n = 94
YES (%)	31	26
NO (%)	64	68

NurOwn® (MSC-NTF Cells) vs Placebo: Odds Ratio (OR): 1.330 (95% CI 0.632 to 2.798), p = 0.453, Chi-squared

Population analysed: The modified intent-to-treat (mITT) population was defined as all participants who were randomized, treated and had at least three ALSFRS-R assessments: one pre-treatment assessments of ALSFRS-R prior to the baseline assessment, a baseline assessment and one post-treatment assessment.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: from the screening visit through the end of the study period (28 weeks after first treatment). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NurOwn® (MSC-NTF Cells)	23 of 95 (24.2%)	93 of 95 (97.9%)	10 of 95
Placebo	17 of 94 (18.1%)	92 of 94 (97.9%)	4 of 94

Limitations and caveats (from the sponsor): This trial had a unique and atypical trial population that included more participants than anticipated with advanced ALS, who had a low ALSFRS-R score. As compared with recent large ALS clinical trials, this study population is an outlier, with a mean overall ALSFRS-R score at baseline lower than other studies, and this impacted the power of this study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Merit E. Cudkowicz, MD principal investigator

Massachusetts General Hospital

Robert H. Brown, MD, PhD principal investigator

UMass Medical School

Anthony J. Windebank, MD principal investigator

Mayo Clinic

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NurOwn® (MSC-NTF cells) and Bone Marrow aspiration in people with Amyotrophic Lateral Sclerosis (ALS), run by Brainstorm-Cell Therapeutics at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo (time frame: 28 weeks following the first intrathecal injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03280056.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Feb 2024.