An Open Label Study of the Effects of Eculizumab in CD59 Deficiency

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Hadassah Medical Organization.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Mevorach Dror, Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01579838
First received: February 23, 2012
Last updated: April 17, 2012
Last verified: April 2012
  Purpose

The investigators have identified patients with CD59 deficiency that suffers from chronic hemolysis and peripheral demyelinating disease. It was shown that complement terminal pathway can cause inflammation in the peripheral nervous system. Complement can greatly increase the immune attack in the nerves. Eculizumab has already been shown to be effective in a rare blood disorder known as paroxysmal nocturnal hemoglobinuria (PNH). Attacks of PNH are also mediated through complement. Therefore, the investigators of this study are investigating whether by 'turning off' complement in CD59 deficiency, further attacks of hemolysis and nerve injury can be avoided and whether the neurological status will ameliorate.


Condition Intervention Phase
Chronic Hemolysis
Drug: Eculizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study of the Effects of Eculizumab in CD59 Deficiency

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Whether Eculizumab reduces chronic hemolysis [ Time Frame: 8 months ] [ Designated as safety issue: No ]

    The primary objectives of this study are to determine:

    Whether Eculizumab reduces chronic hemolysis as judged by LDH levels, and haptoglobin, and level of hemoglobin.


  • Steroid and iv IgG cumulative dosage [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Cumulative steroid and IgG dosage before and after treatment

  • Safety. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    Whether the subjects develop known or possible related side effect to the treatment. The number of participants that develop adverse effects will be determined. reports from parents will be taken avery other week and documented clini or hospital visits will be included.

  • Whether Eculizumab ameliorates the neurological status compared to one month before treatment [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    The neurological status in the last month prior to treatment will be determined followed by neurological staus examination every two weeks.


Secondary Outcome Measures:
  • Whether eculizumab maintains or improves limbs motion [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Whether there is a neurological amelioration

  • function and quality of life as measured by a variety of established disability scales. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    we will be using evry other week parents report of his clinical condition. We will use modified SF36 and local questionairre.

  • The severity of an individual attack and the degree of recovery. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Levels of membrane attack complex [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
    This will be measured using flow cytometry for the presence of membrane attack complex on neutrophild and res blood cells.


Estimated Enrollment: 5
Study Start Date: February 2012
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab
Eculizumab will be administrated according to known protocols.
Drug: Eculizumab
PNH and or atypical TTP classical protocols
Other Name: Soliris

Detailed Description:

It has been shown in some scientific studies that lack of CD59 in the context of the disease paroxysmal nocturnal hemoglobinuria (PNH)leads to chronic hemolysis. The investigators have identified patients wirh CD59 deficiency that suffers from chronic hemolysis and demyelinating disease. It was shown that complement terminal pathway can cause cause inflammation in nervous system. Complement can greatly increase the immune attack in the nerves. Eculizumab has already been shown to be effective in a rare blood disorder known as PNH. Attacks of PNH are also mediated through complement. Therefore, the investigators of this study are investigating whether by 'turning off' complement in CD59 deficiency, further attacks of hemolysis and nerve injury can be avoided.

The primary (most important) objectives of this study are to determine:

Whether Eculizumab ameliorate the neurological condition documented in the last month before treatment and whether it reduces the relapse frequency in patients with relapsing chronic inflammatory demyilinating polyneuropathy. The number of attacks during the one year treatment period will be compared to the number of attacks that occurred prior to initiation of eculizumab treatment. For patients with more than 2 year disease duration, the average number of attacks in the preceding 2 years will be calculated. For patients with less than 2 years disease duration the number of attacks in the preceding year will be used.

Whether Eculizumab reduces chronic hemolysis as judged by LDH levels, and haptoglobin, and level of hemoglobin. the same for corticosteroids and or I.V. IgG consumption before and after treatment with eculizumab.

The safety profile of eculizumab in patients with CD59 deficiency will be determined by parents report evry other week, documentation of clinic referral and hospitalizations. The number of participants with advers events will be determined.

The secondary objectives are to determine:

Whether eculizumab maintains or improves limbs motion, function and quality of life as measured by a variety of established disability scales like the modified SF36 and like a questionaire developed for this age group. The investigators will also assess the severity of an individual attack and the degree of recovery.

How the drug behaves in the patient's blood by measuring the presence of membrane attack complex on neutrophils and red blood cells.

  Eligibility

Ages Eligible for Study:   2 Months to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CD59 deficiency

Exclusion Criteria:

  • recent exposure to meningococcal infections
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01579838

Contacts
Contact: Dror Mevorach, MD mevorachd@hadassah.org.il

Locations
Israel
Hadassah Medical Center Recruiting
Jerusalem, Israel, 91120
Contact: Dror Mevorach, MD    972-2- 6777317    mevorachd@hadassah.org.il   
Principal Investigator: Dror Mevorach, MD         
Sponsors and Collaborators
Hadassah Medical Organization
Investigators
Principal Investigator: Dror Mevorach, MD hmo
  More Information

No publications provided

Responsible Party: Mevorach Dror, Head of Medicine and head of Rheumatology Research Center, Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01579838     History of Changes
Other Study ID Numbers: CD59-Mevorach-1
Study First Received: February 23, 2012
Last Updated: April 17, 2012
Health Authority: Israel: "Hadassah Medical Organization"

Additional relevant MeSH terms:
Hemolysis
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014