T-Regulatory Cells in Amyotrophic Lateral Sclerosis

NCT03241784 | Unknown Phase 1 FDA Drug

• 1 other identifier: Pro00013616
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label pilot study to determine the safety and tolerability of infusions of autologous CD4+ CD25+ regulatory T cells with concomitant subcutaneous IL-2 injections in 4 subjects with ALS.

Conditions

ALS (Amyotrophic Lateral Sclerosis)

Keywords

ALS; T-Regulatory Cells

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Clinical laboratory blood tests are standard to assure safety in clinical trials. Complete blood count, chemistry, liver function, throxine (T4) and thyroid stimulating hormone (TSH) will be assessed for normal reference ranges and abnormal (not clinically significant) results. Clinically abnormal results will be documented as adverse events as per CTCAE v4.0.

  Baseline to two years

Secondary Outcomes (5)

• AALS (Appel ALS) Scale

  Baseline to week 15

• ALSFRS-R (ALS Functional Rating Scale-Revised)

  Baseline to week 15

• T-Regulatory Cells

  Baseline to 3 months post treatment for a total of two years from baseline

• Treg Suppression

  Baseline to 3 months post treatment for a total of two years from baseline

• TH17 and Th1 lymphocytes

  Baseline to 3 months post-treatment for a total of two years from baseline

Other Outcomes (3)

• Pulmonary FVC - Exploratory Measure

  Baseline to 3 months post-treatment for a total of two years from baseline

• Pulmonary MIP - Exploratory Measure

  Baseline to 3 months post-treatment for a total of two years from baseline

• Tracheostomy- Exploratory Measure

  Baseline to 3 months post-treatment for a total of two years from baseline

Study Arms (1)

Treatment arm

EXPERIMENTAL

All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week.

Biological: Autologous T-regulatory lymphocytes; Biological: Interleukin-2

Interventions

Autologous T-regulatory lymphocytes BIOLOGICAL

intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg.

Treatment arm

Interleukin-2 BIOLOGICAL

Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.

Also known as: IL-2

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older.
• Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
• Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days (riluzole-naïve subjects are permitted in the study).
• Capable of providing informed consent and following trial procedures.
• Geographically accessible to the site.
• Women must not be able to become pregnant (e.g. post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
• Subjects must agree not to take live attenuated vaccines (including seasonal flu vaccine) 30 days before blood collection.
• Available autologous Tregs product with greater than or equal to 50% expression of CD4, CD25 and FoxP3 determined by flow-cytometry.
• Subjects must have been previously evaluated and followed clinically by a neuromuscular specialist at Houston Methodist Neurological Institute
• Normal Alanine aminotransferase level (ALT)
• Normal Serum creatinine level

You may not qualify if:

• Prior use of cells therapies
• Concurrent use of other experimental ALS therapies
• Pregnant or breastfeeding or planning to become pregnant or planning a partner's pregnancy.
• Other unstable medical or psychiatric illness
• Known immune deficiency or history of lymphoma or leukemia
• History of lymphopenia.
• History of acquired or inherited immune deficiency syndrome, including leukopenia.
• History of severe untreated chronic obstructive sleep apnea.
• FVC less than 50% predicted at screening.
• Exposure to any other agent currently under investigation for the treatment of subjects with ALS (off-label use or investigational) within 30 days of the Baseline Visit.
• The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to the PI's judgment, or a history of active substance abuse within the prior year.
• Clinically significant history of cardiac, oncologic, hepatic, or renal dysfunction, or other medically significant illness.
• The presence of any immunologic or autoimmune disease
• Severe cardiac dysfunction defined clinically, or as a left ventricular ejection fraction less than 40% of predicted or abnormal EKG findings.

Sponsors & Collaborators

• Stanley H. Appel, MD: lead

Study Sites (1)

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Stanley H Appel, MD

  Houston Methodist Neurological Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: TMHPO Chairman & Principal Investigator

Model Details: Autologous infusion of expanded T-regulatory lymphocytes during early and late phases of ALS disease in patients with varying rates of disease progression.

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 7, 2017
• Study Start: May 16, 2016
• Primary Completion: February 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 26, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)