Immunosuppression in Amyotrophic Lateral Sclerosis (ALS)

NCT01884571 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB00064218NIP-ALS-20132013P000981
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, 15-month study evaluating the effect of immunosuppression treatment on the rate of change on the ALS Functional Rating Scale (Revised) (ALSFRS-R) score in up to 33 subjects with Amyotrophic Lateral Sclerosis (ALS).

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Immunosuppression; ALS; Neuromuscular Disorders

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Average Increase in ALSFRS-R Score of One Point Per Month

  The ALS Functional Rating Scale - Revised (ALSFRS-R) is an ordinal rating scale (0 through 4) used to determine the ALS patient's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score (best of 48) from four sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). A clinical response is defined as a rate of change of ALSFRS-R of +6 points over 6 months (mean of +1 point per month), where typically patients with ALS have a decline in ALSFRS-R by an average of -1/month.

  Pre-Treatment Period (3 months prior to the start of treatment, 2 months prior to the start of treatment, and 1 month prior to the start of treatment), Treatment Period (Day 1 and then monthly until Month 6)

Secondary Outcomes (7)

• Mean Rate of Change of ALSFRS-R Scores During Treatment Compared to Pre-Treatment

  Pre-Treatment Period (3 months prior to the start of treatment, 2 months prior to the start of treatment, and 1 month prior to the start of treatment), Treatment Period (Day 1 and then monthly until Month 6)

• Mean Rate of Change of Slow Vital Capacity (SVC) During Treatment Compared to Pre-Treatment

  Pre-Treatment Period (3 months prior to the start of treatment, 2 months prior to the start of treatment, and 1 month prior to the start of treatment), Treatment Period (Day 1 and then monthly until Month 6)

• Mean Rate of Change of Hand-Held Dynamometry (HHD) During Treatment Compared to Pre-Treatment

  Pre-Treatment Period (3 months prior to the start of treatment, 2 months prior to the start of treatment, and 1 month prior to the start of treatment), Treatment Period (Day 1 and then monthly until Month 6)

• Mean Rate of Change in Grip Strength Treatment Compared to Pre-Treatment

  Pre-Treatment Period (3 months prior to the start of treatment, 2 months prior to the start of treatment, and 1 month prior to the start of treatment), Treatment Period (Day 1 and then monthly until Month 6)

• Mean Rate of Change of T-cell Subsets in Blood Treatment Compared to Pre-Treatment

  Pre-Treatment Period (2 months prior to the start of treatment), Treatment Period (Day 1 and Months 1, 2, 4, 6)

Study Arms (1)

Immunosuppression Regimen

EXPERIMENTAL

Basiliximab Methylprednisolone Prednisone Tacrolimus Mycophenolate mofetil

Drug: Basiliximab; Drug: Methylprednisolone; Drug: Prednisone; Drug: Tacrolimus; Drug: Mycophenolate mofetil

Interventions

Basiliximab DRUG

20 mg, IV (in the vein) on day 1 and 4.

Also known as: Simulect

Immunosuppression Regimen

Methylprednisolone DRUG

125 mg, IV (in the vein) on day 1.

Also known as: Solumedrol

Immunosuppression Regimen

Prednisone DRUG

60 mg PO (by mouth) on days 2-7, 40 mg PO days 8-14, 20 mg PO days 15-21, and 10mg PO days 22-28.

Also known as: Deltasone, Orasone

Immunosuppression Regimen

Tacrolimus DRUG

1-5 mg PO, twice a day (BID) days 2-180.

Also known as: Prograf

Immunosuppression Regimen

Mycophenolate mofetil DRUG

500 mg PO, BID days 2-7, 500 mg PO each morning and 1000 mg each night, days 8-14, 1000 mg PO BID days 15-180.

Also known as: Cellcept

Immunosuppression Regimen

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18-65 years of age.
• ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial Criteria.
• Symptom onset ≤ 24 months from screening visit.
• A score of ≥38 on the Revised ALS Functional Rating Scale.
• Slow vital capacity (SVC) measure \>80% of predicted for gender, height and age at screening.
• Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to the screening visit (riluzole-naïve subjects are permitted in the study).
• Negative tuberculosis (TB) test within 3 months of Screening Visit.
• Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (i.e., no bleeding disorder, allergy to local anesthetics, or a skin infection at or near the LP site).
• Capable of providing informed consent and following study procedures.
• 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.
• Women of childbearing potential must have a negative pregnancy test at screening and be non-lactating.
• Geographic accessibility to the study site.
• Male or female patients age 18 or older.
• ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial Criteria.
• Symptom onset \>24 months from screening visit.

You may not qualify if:

• Prior use of basiliximab, solumedrol, prednisone, tacrolimus or mycophenolate mofetil within 30 days of the Screening Visit.
• Known allergy or sensitivity to basiliximab, solumedrol, prednisone, tacrolimus or mycophenolate mofetil or a formulation of one of these drugs.
• Treatment with an immunosuppressant medication within 30 days of the Screening Visit.
• Active peptic ulcer disease.
• Any medical disorder that would make immunosuppression contraindicated including, but not limited to, human immunodeficiency virus (HIV), tuberculosis, or evidence of active cytomegalovirus (CMV) or infection.
• Subjects who have a diaphragm pacing system (DPS).
• Women who are pregnant, breastfeeding, or planning to become pregnant in the next 12 months.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Use of invasive or non-invasive mechanical ventilation (including Continuous Positive Airway Pressure (CPAP) or Bi-level Positive Airway Pressure (BiPAP)) for any part of the day or night prior to the Screening Visit (participants with symptom onset within past 24 months only).
• Exposure to any other agent currently under investigation for the treatment of patients with ALS (off-label use or investigational) within 30 days of the Screening Visit.
• Inability to safely complete study activities based on the discretion of the site investigator.

Sponsors & Collaborators

• Emory University: lead
• ALS Association: collaborator

Study Sites (3)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Related Publications (1)

• Fournier CN, Schoenfeld D, Berry JD, Cudkowicz ME, Chan J, Quinn C, Brown RH, Salameh JS, Tansey MG, Beers DR, Appel SH, Glass JD. An open label study of a novel immunosuppression intervention for the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):242-249. doi: 10.1080/21678421.2017.1421666. Epub 2018 Jan 8.

  PMID: 29308669 DERIVED

Related Links

• Northeast ALS Consortium Website

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Neuromuscular Diseases

Interventions

Basiliximab; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisone; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Jonathan Glass, MD
• Organization: Emory University

jglas03@emory.edu

404-727-3507

Study Officials

• Jonathan D Glass, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Christina N Fournier, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Emory ALS Clinic

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: June 24, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: November 6, 2017
• Results First Posted: July 31, 2017

Record last verified: 2017-11

Locations

US (3)