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

NCT ID: NCT01579838

Last Updated: 2012-04-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-03-31

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.

Conditions

Chronic Hemolysis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eculizumab

Eculizumab will be administrated according to known protocols.

Group Type: EXPERIMENTAL

Eculizumab

Intervention Type: DRUG

PNH and or atypical TTP classical protocols

Interventions

Eculizumab

PNH and or atypical TTP classical protocols

Intervention Type: DRUG

Other Intervention Names

Soliris

Eligibility Criteria

Inclusion Criteria

• CD59 deficiency

Exclusion Criteria

• recent exposure to meningococcal infections

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

Mevorach Dror

Head of Medicine and head of Rheumatology Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dror Mevorach, MD

Role: PRINCIPAL_INVESTIGATOR

hmo

Locations

Hadassah Medical Center

Jerusalem, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Dror Mevorach, MD

Role: CONTACT

mevorachd@hadassah.org.il

Facility Contacts

Dror Mevorach, MD

Role: primary

mevorachd@hadassah.org.il

972-2- 6777317

References

Mevorach D, Reiner I, Grau A, Ilan U, Berkun Y, Ta-Shma A, Elpeleg O, Shorer Z, Edvardson S, Tabib A. Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation. Ann Neurol. 2016 Nov;80(5):708-717. doi: 10.1002/ana.24770. Epub 2016 Sep 19.

Reference Type: DERIVED

PMID: 27568864 (View on PubMed)

Other Identifiers

CD59-Mevorach-1

Identifier Type: -

Identifier Source: org_study_id