Pilot Study of alpha1-antitrypsin to Treat Neuromyelitis Optica Relapses

NCT02087813 | Withdrawn Phase 1

• 1 other identifier: IRB-27176
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Neuromyelitis Optica (NMO) is a rare, devastating demyelinating disease of the central nervous system (CNS) that has different causes and treatments from the more common demyelinating disease multiple sclerosis (MS). Current NMO therapies are nonspecific and have varying and often suboptimal benefit. The investigators will evaluate whether use of alpha1-antitrypsin (A1AT, an FDA-approved medication for patients with congenital deficiency of A1AT associated with emphysema) can benefit acute attacks of NMO, improving patient disability and quality of life.

Conditions

Neuromyelitis Optica

Keywords

neuromyelitis optica; optic neuritis; longitudinally extensive transverse myelitis

Outcome Measures

Primary Outcomes (1)

• Mean change in disability from baseline/nadir to week 24 as assessed by Opticospinal Impairment Score (OSIS) subscale.

  Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.

Secondary Outcomes (4)

• Mean change in disability from baseline/nadir to week 24 as assessed by Expanded Disability Status Scale (EDSS).

  Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.

• For patients experiencing optic neuritis, mean change in visual acuity from baseline/nadir to week 24 as assessed by Sloan 2.5% low contrast visual acuity chart.

  Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.

• Mean change in retinal nerve fiber layer from baseline/nadir to week 24 as assessed by optical coherence tomography (OCT).

  Baseline and Week 24

• Mean change in length of spinal cord lesion from baseline/nadir to week 24 as assessed by magnetic resonance imaging (MRI) T2 sequences.

  Baseline, Week 24

Other Outcomes (6)

• Suicidality as a Measure of Safety and Tolerability

  Screening, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.

• Serum biomarkers, including cytokines, elastase level, A1AT level, neutrophil elastase activity.

  Baseline, Week 1: Day 2, Week 2, 3, 4, 8, 16, and 24.

• Cerebral Spinal Fluid (CSF) biomarkers, including neurofilament, GFAP, MBP, neutrophil elastase activity, A1AT level, cytokines.

  Baseline and Week 8

Study Arms (2)

A1AT

EXPERIMENTAL

Alpha1-antitrypsin 120mg/kg once weekly for a total of 4 doses, to be given intravenously. This will be given in addition to standard of care 3-5 days of 1000mg IV methylprednisolone.

Drug: Alpha1-antitrypsin; Drug: methylprednisolone

Standard of care

ACTIVE COMPARATOR

Patients that do not wish to receive study treatment but agree to otherwise follow study protocol will also be enrolled in an observational cohort. They will receive the standard of care 3-5 days 1000mg IV methylprednisolone.

Drug: methylprednisolone

Interventions

Alpha1-antitrypsin DRUG

Also known as: ARALAST NP, alpha1-proteinase inhibitor

A1AT

methylprednisolone DRUG

3-5 days 1000mg IV methylprednisolone at first presentation with acute attack.

Also known as: Solu-Medrol

A1AT; Standard of care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent.
• Age ≥18 and ≤ 75 years.
• Diagnosis of NMO or NMO spectrum disorder (NMOSD). The diagnosis of NMO will conform to the 2006 Wingerchuk criteria.1, 2 The diagnosis of NMOSD will include patients with relapsing optic neuritis and aquaporin-4 antibody (AQP4) seropositivity or patients with relapsing longitudinally extensive transverse myelitis and AQP4 seropositivity.2-5 NMO and NMOSD will be collectively referred to as NMO.
• AQP4-antibody positivity.
• Present with an acute NMO attack (see definition below).
• Patients must not have a history of clinically significant infusion reactions with administration of biologic agents.
• If on chronic treatment for NMO, treatment was initiated at least 3 months earlier and medication dose is stable. Additional restrictions will be placed on changes in concomitant symptomatic medications.
• A female subject of childbearing potential must have a negative serum pregnancy test at the screening visit and agree to use a medically reliable method of contraception (e.g., barrier with either spermicide or hormonal contraception) until study completion.
• Agree to answer the questions on the Columbia Suicide Severity Rating Scale at each specified visit.

You may not qualify if:

• A woman who is pregnant, breastfeeding, or planning pregnancy.
• If the patient is enrolled in any other experimental trial or on other experimental therapy.
• If the patient has a known IgA deficiency with IgA-antibodies.
• Any medical condition or clinically significant laboratory abnormality that in the Investigator's judgment may affect the patient's ability to safely complete the study.
• Acute attack:
• The occurrence of new or worsening neurological symptoms consistent with optic neuritis, transverse myelitis, or a brain lesion that develop acutely (i.e., patients must present within 7 days of symptom onset).
• The symptoms must persist for at least 48 hours, are not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to concomitant medications).
• The symptoms must be accompanied by sensory, motor or visual acuity objective deficits, which must be verified by the examining physician.
• A single episode of a paroxysmal symptom (e.g., tonic spasm) is not a relapse; however, the new onset of multiple occurrences of a paroxysmal symptom over at least 48 hours can be a relapse if accompanied by a new, corresponding objective deficit.
• Sensory symptoms with no change on clinical examination, fatigue, mood change, or bladder or bowel urgency or incontinence will not be sufficient to establish a relapse.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Neuromyelitis Optica; Optic Neuritis

Interventions

alpha 1-Antitrypsin; Methylprednisolone; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Alexandra L Goodyear, MD, MS

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2014
• First Posted: March 14, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2016
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

US (1)