C1-esterase Inhibitor (Cinryze) for Acute Treatment of Neuromyelitis Optica Exacerbation

NCT01759602 | Completed Phase 1 Results DMC

• 1 other identifier: NA_00078437
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective is to evaluate the tolerability/safety and preliminary efficacy of CINRYZE® (C1 esterase inhibitor \[human\]) as add-on therapy for treatment of acute optic neuritis and/or transverse myelitis in NMO and NMOSD. Primary Objective: To evaluate the safety and tolerability of 3-5 doses of 1000 - 2000 Units intravenous CINRYZE in NMO/NMOSD patients during an acute exacerbation. Secondary Objectives:

• To determine the frequency of adverse events with CINRYZE in this patient population.
• To determine the effect of CINRYZE on NMO clinical scores (Expanded Disability Status Scale and Low Contrast Visual Acuity).
• To compare the change in MRI lesion size and extent following a course of CINRYZE.

Conditions

Neuromyelitis Optica

Keywords

Neuromyelitis optica; Devic's disease; NMO; Devic

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Safety Events During Hospitalization

  Over the course of hospitalization for the acute NMO exacerbations, subjects will be monitored daily for frequency of adverse events.

  5-21 days

Secondary Outcomes (4)

• Frequency of Serious Adverse Events.

  5-21 days

• Percentage of Subjects Withdrawing Due to Adverse Events.

  5-21 days

• Change From Baseline in Hematology, Chemistry, and Urinalysis Parameters.

  5-21 days

• Expanded Disability Status Score (EDSS)

  participants were followed for the duration of hospital stay ranging from 5-21 days, an average of 13 days; EDSS assessment was administered at discharge

Study Arms (1)

C1-esterase inhibitor (Cinryze)

EXPERIMENTAL

This is a phase 1b open-label, interventional proof-of-concept study in patients with neuromyelitis optica (NMO) in which all subjects will receive 3 daily infusions of 2000 Units of intravenous CINRYZE at the onset of an NMO exacerbation in addition to standard of care high-dose steroids, plus an additional 2 infusions of 1000 Units of intravenous CINRYZE during a second treatment phase with plasma exchange, if necessary.

Drug: C1-esterase inhibitor (Cinryze)

Interventions

C1-esterase inhibitor (Cinryze) DRUG

Also known as: Cinryze

C1-esterase inhibitor (Cinryze)

Eligibility Criteria

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

You may qualify if:

• Able and willing to provide written informed consent.
• years of age.
• New acute optic neuritis and/or transverse myelitis. A clinical event is defined as an episode of inflammation in the spinal cord and/or optic nerve leading to neurologic symptoms not ascribed to another disease process.
• Diagnosis of NMO according to the 2006 revisions of the Wingerchuk diagnostic criteria for NMO (Wingerchuk, 2006), or AQP4 positive NMOSD per the EFNS Guidelines. For NMO, subjects must have two absolute criteria:
• optic neuritis
• myelitis and at least two of three supportive criteria:
• presence of a contiguous spinal cord MRI lesion extending over three or more vertebral segments,
• MRI criteria NOT satisfying the revised McDonald diagnostic criteria for MS \[Polman, 2011\]
• NMO-IgG (AQP4) in serum. For NMOSD, subjects must have longitudinally extensive transverse myelitis (LETM) recurrent isolated optic neuritis (RION)/bilateral optic neuritis (BON), or opticospinal multiple sclerosis (OSMS) that is AQP4 antibody positive.
• A female subject is eligible to enter the study if she is:
• A. Not pregnant or nursing; B. Of non-childbearing potential (i.e. women who have had a hysterectomy, are post-menopausal, which is defined as \>2 years without menses or, in female subjects who have been post-menopausal for \<2 years, must be confirmed with Follicle Stimulating Hormone (FSH) and estradiol levels), have both ovaries surgically removed or have current documented tubal ligation) OR Of child-bearing potential (i.e. women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea (even severe), women who are perimenopausal or have just begun to menstruate.
• C. Subject has a negative serum pregnancy test at screening and agrees to one of the following:
• Complete abstinence from intercourse for the period from consent into the study until 6 months after the last dose of investigational product; or,
• Consistent and correct use of one of the following acceptable methods of birth control for the period from consent into the study until 6 months after the last dose of investigational product:
• i. Oral contraceptives (either combined or progesterone only) ii. Injectable progesterone iii. Levonorgestrel implants iv. Estrogenic vaginal ring v. Percutaneous contraceptive patches vi. Intrauterine device (IUD) or intrauterine system (IUS) with a documented failurerate of \<1% per year vii. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study; this male must be the sole partner for the subject viii. Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository).

You may not qualify if:

• Current evidence or known history of clinically significant infection including:
• Chronic or ongoing active infectious disease requiring long term systemic treatment such as, but not limited to: PML, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, or active hepatitis C.
• Previous serious opportunistic or atypical infections.
• History of positive serology for hepatitis B.
• Prior history, or suspicion, of tuberculosis (TB)
• History of positive serology for HIV.
• History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral contusion, spinal cord compression).
• History or presence of myelopathy due to spinal cord compression by disc or vertebral disease.
• Past or current history of medically significant adverse effects (including allergic reactions) from:
• a. Corticosteroids
• Past or current malignancy, except for
• Cervical carcinoma Stage 1B or less
• Non-invasive basal cell and squamous cell skin carcinoma
• Cancer diagnoses with a duration of complete response (remission) \>5 years
• A history of hematologic malignancy excludes a subject from participation, regardless of response.

Sponsors & Collaborators

• Michael Levy: lead
• ViroPharma: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Tradtrantip L, Asavapanumas N, Phuan PW, Verkman AS. Potential therapeutic benefit of C1-esterase inhibitor in neuromyelitis optica evaluated in vitro and in an experimental rat model. PLoS One. 2014 Sep 5;9(9):e106824. doi: 10.1371/journal.pone.0106824. eCollection 2014.

  PMID: 25191939 DERIVED

Related Links

• Johns Hopkins NMO Research Lab

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Complement C1 Inhibitor Protein; SERPING1 protein, human

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Results Point of Contact

• Title: Michael Levy, MD, PhD
• Organization: Johns Hopkins University

mlevy@jhmi.edu

443-287-4412

Study Officials

• Michael Levy, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Assistant Professor

Study Record Dates

• First Submitted: December 29, 2012
• First Posted: January 3, 2013
• Study Start: January 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 18, 2014
• Results First Posted: July 18, 2014

Record last verified: 2014-07

Locations

US (1)