Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis (ALS)

• ClinicalTrials.gov Identifier: NCT03268603
• Recruitment Status: Recruiting
• First Posted: August 31, 2017
• Last Update Posted: April 11, 2019
• Sponsor: Mayo Clinic
• Collaborator: State of Minnesota Regenerative Medicine Minnesota
• Information provided by (Responsible Party): Nathan P. Staff, Mayo Clinic

Tracking Information

• First Submitted Date: August 30, 2017
• First Posted Date: August 31, 2017
• Last Update Posted Date: April 11, 2019
• Actual Study Start Date: October 10, 2017
• Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2017)

Number of Adverse Events [ Time Frame: approximately 2 years ]

Number of adverse events will be recorded from the time of enrollment until the end of the follow-up period or, in the case of early withdrawal, to the time of study withdrawal.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03268603 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: August 30, 2017)

Change in slope of ALS Functional Rating Scale - Revised (ALSFRS-R) [ Time Frame: baseline, approximately 1 year ]

The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis (ALS)
• Official Title: A Phase II Study of Intrathecal Autologous Adipose-derived Mesenchymal Stromal Cells for Amyotrophic Lateral Sclerosis

Brief Summary

The purpose of this study is to determine the safety and efficacy of intrathecal treatment delivered to the cerebrospinal fluid (CSF) of mesenchymal stem cells in ALS patients every 3 months for a total of 4 injections over 12 months.

Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown into a number of different kinds of cells. In this study, MSCs will be taken from the subject's body fat and grown. CSF is the fluid surrounding the spine.

The use of mesenchymal stem cells is considered investigational, which means it has not been approved by the Food and Drug Administration (FDA) for routine clinical use. However, the FDA has allowed the use of mesenchymal stem cells in this research study.

• Detailed Description: The Goal of the Proposed Study is to perform an open label, 60 subject, Phase II multi-site clinical trial to investigate the safety and efficacy of intrathecal treatment of aaMSCs in ALS. Patients will be treated with 1 x 10^8 aaMSCs every 3 months for a total of 4 intrathecal injections over 12 months. Reduced dose treatments will be allowed based on specific adverse events. Multiple biomarkers will be tracked throughout the clinical trial and correlated with response to treatment. This study will initially be performed at Mayo Clinic in Rochester. Subsequently, the study will expand to the two other Mayo Clinic sites in Arizona and Florida as the manufacturing capabilities are finalized.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• ALS
• Amyotrophic Lateral Sclerosis

Intervention

Drug: Autologous Adipose-derived Mesenchymal Stromal Cells

The investigational product consists of autologous adipose-derived Mesenchymal Stromal Cells (MSCs), suspended in 5-10 mL Lactated Ringer's. The MSC are provided in a sterile syringe labelled with appropriate patient and product identifiers ready for intrathecal injection.

Study Arms

Experimental: Mesenchymal Stromal Cells

Autologous Adipose-derived Mesenchymal Stromal Cells (aaMSCs) will be administered intrathecally at a single dose in a volume of 5-10 mL, all patients will receive 1 x 10^8 intrathecal aaMSCs at the first injection (Visit 4). Subsequent doses may be reduced to 5 x 10^7, based on Dose Modification Rules. One further dose reduction to 1 x 10^7 may occur in later injections.

Intervention: Drug: Autologous Adipose-derived Mesenchymal Stromal Cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 30, 2017): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2019
• Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• All patients will have ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the World Federation of Neurology criteria for the diagnosis of ALS.
• Examination and neurophysiological testing confirm a pure motor syndrome compatible with the diagnosis of ALS. All other possible causes of weakness have been excluded by extensive investigations.
• Age greater than 18 years, if female, must be post-menopausal, had a hysterectomy, or agree to two forms of birth control.
• Permanent resident or citizen of the United States.
• Geographic accessibility to the study site and willingness and ability to comply with follow-up.
• History of a chronic onset of a progressive motor weakness of less than two years duration.
• Subjects must be taking a stable dose of riluzole for at least 30 days prior to enrolment or not be on riluzole, and not have been on it for at least 30 days prior to enrolment (riluzole-naïve subjects are permitted in the study).
• Able to comply with protocol requirements, including MRI testing.
• Can provide written informed consent.

Exclusion Criteria:

• Any clinically significant medical condition (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the opinion of the investigator, would compromise the safety of patient.
• Pulmonary Slow Vital Capacity (SVC) less than 65% of predicted for age, gender, and body type.
• Autoimmunity, including Crohn's disease or rheumatoid arthritis
• Current use of immunosuppressant medication or use of such medication within 4 weeks of Screening visit (Visit 1).
• Malignancy 5 years prior to enrollment, including melanoma,with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline).
• Active systemic or local infection near the lumbar puncture site.
• Inability to lie flat for the duration of intrathecal cell transplantation, or inability to tolerate study procedures for any other reason.
• Other active systemic disease as defined by laboratory abnormalities delineated in Appendix IV.
• Use of herbal medications or other unapproved drugs
• Enrolled in an investigational drug trial within 30 days of baseline visit
• Prior stem cell therapy of any kind
• Kokmen Short Test of Mental Status score <32
• Presence of a tracheostomy
• Ventilator dependent
• Pregnancy
• Men or women of childbearing potential who are unwilling to employ adequate contraception

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michelle M Turner; 507-284-2676; RSTALSRESEARCH@mayo.edu

Contact: Carol Denny; 507-284-2676; RSTALSRESEARCH@mayo.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03268603
• Other Study ID Numbers: 15-008008; UL1TR000135 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Nathan P. Staff, Mayo Clinic
• Study Sponsor: Mayo Clinic
• Collaborators: State of Minnesota Regenerative Medicine Minnesota

Investigators

• Principal Investigator: Nathan P Staff, MD, PhD; Mayo Clinic
• Principal Investigator: Anthony J Windebank, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: April 2019