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

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

Sponsors

Lead Sponsor: Hadassah Medical Organization

Source Hadassah Medical Organization
Brief Summary

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.

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.

Overall Status Unknown status
Start Date February 2012
Completion Date March 2013
Primary Completion Date March 2013
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Whether Eculizumab reduces chronic hemolysis 8 months
Steroid and iv IgG cumulative dosage 8 months
Safety. 8 months
Whether Eculizumab ameliorates the neurological status compared to one month before treatment 8 months
Secondary Outcome
Measure Time Frame
Whether eculizumab maintains or improves limbs motion 8 months
function and quality of life as measured by a variety of established disability scales. 8 months
The severity of an individual attack and the degree of recovery. 8 months
Levels of membrane attack complex 8 months
Enrollment 5
Condition
Intervention

Intervention Type: Drug

Intervention Name: Eculizumab

Description: PNH and or atypical TTP classical protocols

Arm Group Label: Eculizumab

Other Name: Soliris

Eligibility

Criteria:

Inclusion Criteria:

- CD59 deficiency

Exclusion Criteria:

- recent exposure to meningococcal infections

Gender: All

Minimum Age: 2 Months

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Dror Mevorach, MD Principal Investigator hmo
Overall Contact

Last Name: Dror Mevorach, MD

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Hadassah Medical Center Dror Mevorach, MD 972-2- 6777317 [email protected] Dror Mevorach, MD Principal Investigator
Location Countries

Israel

Verification Date

April 2012

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Hadassah Medical Organization

Investigator Full Name: Mevorach Dror

Investigator Title: Head of Medicine and head of Rheumatology Research Center

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Eculizumab

Type: Experimental

Description: Eculizumab will be administrated according to known protocols.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov