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

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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Coversin

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 Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Coversin treatment; Coversin - 22.5mg followed by 45mg for 6 months.	Drug: Coversin; Coversin - 22.5mg followed by 45mg for 6 months.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AKARI Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2018
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: AK585

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No