Coversin in PNH in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms

Study Overview
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Brief Summary
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Coversin in Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.

Detailed Description
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Coversin, a small protein complement C5 inhibitor which prevents the cleavage of C5 by C5 convertase into C5a and C5b, will be used in an open label, non-comparative clinical trial in patients with PNH and proven resistance to eculizumab due to C5 polymorphisms. Patients will be treated with Coversin by daily subcutaneous injection for 6 months in order to determine the safety and efficacy of the drug in these circumstances. If satisfactory control of the PNH is achieved, and at the discretion of the Principal Investigator (PI), patients will have the option of remaining on Coversin and being entered into the long term follow-up study.

Official Title
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CONSENT II: Coversin in Paroxysmal Nocturnal Hemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms

Conditions
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Paroxysmal Nocturnal Hemoglobinuria (PNH)

Intervention / Treatment
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* Drug: Coversin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with known PNH. Aged 18 and above. No upper age limit. Lactate dehydrogenase (LDH) ≥1.5 upper limit of normal. Must agree to use two methods of contraception that are ≥99% effective in preventing pregnancy. Resistance to eculizumab (Soliris®). Voluntary written informed consent. Willing to self-inject Coversin daily. Willing to receive appropriate prophylaxis against Neisseria infection. Willing to avoid prohibited medications for duration of study. Exclusion Criteria: Subjects with body weight <50 kg (110 lb) or >100 kg (220 lb). Pregnancy or breast feeding (females). Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom). Unresolved Neisseria meningitidis infection. Patients who have not received adequate immunization against Neisseria meningitides. Impaired hepatic function. Patients with impaired renal function. Failure to satisfy the Principal Investigator (PI) of fitness to participate for any other reason.

Ages Eligible for Study
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Minimum Age: 18 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: Coversin treatment<br>Coversin - 22.5mg followed by 45mg for 6 months. | Drug: Coversin<br>* Coversin - 22.5mg followed by 45mg for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of serum lactate dehydrogenase (LDH) | Measurement of serum lactate dehydrogenase (LDH) | Baseline to Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lactate dehydrogenase (LDH) | Change in lactate dehydrogenase (LDH) | Day 28 to Day 180 | 
| Change in mean haemoglobin (Hb) | Change in mean haemoglobin (Hb) | Baseline to Day 180 | 
| Change in score on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire | The FACIT Measurement System is a collection of quality of life questionnaires targeted to the management of chronic illness. Change in FACIT-F score, measured on a scale from 0 - 4 (0 = Not at all, 1 = A little bit, 2 = Some-what, 3 = Quite a bit, 4 = Very much). | Baseline to Day 180 | 
| Change in EuroQol 5 Dimensional 5 Level (EQ-5D-5L) score | The descriptive questionnaire comprises of five sections: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each section has 5 levels: No problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that section. The digits for the five sections can be combined into a 5-digit number that describes the patient's health state. | Baseline to Day 180 | 
| Number of blood transfusions | Number of blood transfusions | Baseline to Day 180 |