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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Hemolysis

Intervention / Treatment
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* Drug: Eculizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD59 deficiency Exclusion Criteria: recent exposure to meningococcal infections

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eculizumab<br>Eculizumab will be administrated according to known protocols. | Drug: Eculizumab<br>* PNH and or atypical TTP classical protocols<br>* Other names: Soliris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether Eculizumab reduces chronic hemolysis | 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. | 8 months | 
| Steroid and iv IgG cumulative dosage | Cumulative steroid and IgG dosage before and after treatment | 8 months | 
| Safety. | 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. | 8 months | 
| Whether Eculizumab ameliorates the neurological status compared to one month before treatment | The neurological status in the last month prior to treatment will be determined followed by neurological staus examination every two weeks. | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether eculizumab maintains or improves limbs motion | Whether there is a neurological amelioration | 8 months | 
| function and quality of life as measured by a variety of established disability scales. | we will be using evry other week parents report of his clinical condition. We will use modified SF36 and local questionairre. | 8 months | 
| The severity of an individual attack and the degree of recovery. |  | 8 months | 
| Levels of membrane attack complex | This will be measured using flow cytometry for the presence of membrane attack complex on neutrophild and res blood cells. | 8 months |