Clinical trial NCT02591862: Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)
Official title: Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Haemoglobinuria (PNH)
Lead sponsor: AKARI Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Radboud University Medical Center
First posted: 2015-10-30
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Coversin in Paroxysmal Nocturnal Haemoglobinuria (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 for 2 years.

Please note, 'Coversin' is used throughout, but Nomacopan is the official name/INN.

Please note, the end points were assessed for 6 months, but the adverse events were measured over the 2 year period.

Eligibility criteria: Inclusion Criteria:

* Patients with known Paroxysmal Nocturnal Haemoglobinuria (PNH)
* LDH \>=1.5 Upper Limit of Normal (ULN)
* Resistance to Eculizumab proven by both a recognised C5 polymorphism on genetic screening and complement inhibition on CH50 ELISA of \<100% at concentrations of Eculizumab in excess of 50 μg/mL
* Willing to self-inject Coversin daily or to receive daily subcutaneous injections by a home nurse or in a doctor's office or hospital clinic
* Males or females taking adequate contraceptive precautions if of childbearing potential, 18 - 80 years of age
* Body weight ≥50kg and ≤ 100kg
* The patient has provided written informed consent.
* Willing to avoid prohibited medications for duration of study
* Must agree to take appropriate prophylactic precautions against Neisseria infection.
* Must be counselled regarding the possible reproductive risks of using Coversin and be advised to use an adequate method of contraception pending further data on reproductive toxicology.

Exclusion Criteria:

* Body weight \<50kg or\>100kg
* Pregnancy (females)
* Failure to satisfy the PI of fitness to participate for any other reason
* Known allergy to ticks or severe reaction to arthropod venom (e.g., bee or wasp venom)

Primary outcomes:
measure: Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)
timeFrame: Day 0 and Day 28
measure: Number and Type of Adverse Events (AE)
timeFrame: 2 years
Secondary outcomes:
measure: Measurement of Haemoglobin (Hb) at Days 28, 90, and 180, Absolute and Change From Baseline
timeFrame: Baseline, Day 28, Day 90 and Day 180
measure: Measurement of Haptoglobin (Hp) at Days 28, 90 and 180, Absolute and Change From Baseline
timeFrame: Baseline, Day 28, Day 90 and Day 180
measure: Measurement of Lactate Dehydrogenase (LDH) at Baseline, Day 90 and Day 180
timeFrame: Baseline, Day 90 and Day 180
measure: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score at Days 0, 28, 90 and 180
timeFrame: Day 28, 90 and 180
measure: Change in Quality Of Life Questionnaire (QOQ) Score at Days 0, 28, 90 and 180
timeFrame: Day 28, 90 and 180
measure: Dependency on Blood Transfusion
timeFrame: Day 0 through to study completion (2 years)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Dr Saskia Langemeijer
Study officials:
affiliation: Radboud University Medical Center
name: Petra Dr Muus
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Saskia Dr Langemeijer
role: STUDY_DIRECTOR
References:
citation: Schols S, Nunn MA, Mackie I, Weston-Davies W, Nishimura JI, Kanakura Y, Blijlevens N, Muus P, Langemeijer S. Successful treatment of a PNH patient non-responsive to eculizumab with the novel complement C5 inhibitor coversin (nomacopan). Br J Haematol. 2020 Jan;188(2):334-337. doi: 10.1111/bjh.16305. Epub 2019 Dec 16. No abstract available.