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

Phase 2

Completed

• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Interventions: Drug: Coversin

• Registration Number: NCT03427060
• Lead Sponsor: AKARI Therapeutics

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2018-01-24
• Study First Submitted QC: 2018-02-02
• Study First Posted: 2018-02-09
• Study Start: 2018-05-14
• Primary Completion: 2018-11-15
• Study Completion: 2021-02-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

1. Patients with known PNH.
2. Aged 18 and above. No upper age limit.
3. Lactate dehydrogenase (LDH) ≥1.5 upper limit of normal.
4. Must agree to use two methods of contraception that are ≥99% effective in preventing pregnancy.
5. Resistance to eculizumab (Soliris®).
6. Voluntary written informed consent.
7. Willing to self-inject Coversin daily.
8. Willing to receive appropriate prophylaxis against Neisseria infection.
9. Willing to avoid prohibited medications for duration of study.

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Exclusion Criteria

1. Subjects with body weight <50 kg (110 lb) or >100 kg (220 lb).
2. Pregnancy or breast feeding (females).
3. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom).
4. Unresolved Neisseria meningitidis infection.
5. Patients who have not received adequate immunization against Neisseria meningitides.
6. Impaired hepatic function.
7. Patients with impaired renal function.
8. Failure to satisfy the Principal Investigator (PI) of fitness to participate for any other reason.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Coversin treatment	Coversin	Coversin - 22.5mg followed by 45mg for 6 months.

Primary Outcome Measures

Name	Time	Method
Measurement of serum lactate dehydrogenase (LDH)	Baseline to Day 180	Measurement of serum lactate dehydrogenase (LDH)

Secondary Outcome Measures

Name	Time	Method
Change in score on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire	Baseline to Day 180	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).
Change in EuroQol 5 Dimensional 5 Level (EQ-5D-5L) score	Baseline to Day 180	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.
Change in lactate dehydrogenase (LDH)	Day 28 to Day 180	Change in lactate dehydrogenase (LDH)
Number of blood transfusions	Baseline to Day 180	Number of blood transfusions
Change in mean haemoglobin (Hb)	Baseline to Day 180	Change in mean haemoglobin (Hb)

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States