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Completed

NCT Number: NCT02591862

Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

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

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Key information

Conditions

Paroxysmal Nocturnal Haemoglobinuria (PNH) Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Dr Saskia Langemeijer

Nijmegen, 6525 GA, Netherlands

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Coversin

Drug

Patients enrolled in this protocol will initially be treated with an ablating dose of Coversin and daily repeat maintenance doses calculated according to body weight, the ablating dose to be 0.57mg/kg. Thereafter the daily repeat dose will be titrated according to clinical response and complement inhibition determined by CH50 ELISA. The initial repeat dose will be 25% of the ablating dose and this will be adjusted up or down if necessary once steady state is reached (5 days).

Other names: rVA576, rEV576

Primary outcomes

  1. Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)

    Time frame: Day 0 and Day 28

    LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.

  2. Number and Type of Adverse Events (AE)

    Time frame: 2 years

    The number and type of reported AEs will be recorded as well as the opinion of the Principle Investigator (PI) as to their possible relationship to the study drug.

Secondary outcomes

  1. Measurement of Haemoglobin (Hb) at Days 28, 90, and 180, Absolute and Change From Baseline

    Time frame: Baseline, Day 28, Day 90 and Day 180

    Measuring change in mean Hb from Day 28, Day 90 and Day 180 (absolute and change from baseline)

  2. Measurement of Haptoglobin (Hp) at Days 28, 90 and 180, Absolute and Change From Baseline

    Time frame: Baseline, Day 28, Day 90 and Day 180

    Measuring change in mean Hp from Day 28, Day 90 and Day 180 (absolute and change from baseline)

  3. Measurement of Lactate Dehydrogenase (LDH) at Baseline, Day 90 and Day 180

    Time frame: Baseline, Day 90 and Day 180

    Measuring the change in LDH at Baseline, Day 90 and Day 180. LDH is an indicator of disease progression in patients with PNH and is expected to fall to within 2x upper limit of normal (ULN) within 28 days in successfully treated patients. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L.

  4. Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score at Days 0, 28, 90 and 180

    Time frame: Day 28, 90 and 180

    Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-F) is a 13 item instrument designed to assess fatigue/tiredness and it's impact on daily activities and functioning in a chronic disease setting. The scale for each question in relation to quality of life ranges from 0-4 where 0= not at all, 1= a little bit, 2= somewhat, 3 = quite a bit and 4= very much. An increase in the scale score indicates an improvement in quality of life (less fatigue). A maximum score of 52 is interpreted as no fatigue . Baseline is assumed as 0.0 to demonstrate the change in units.

    The subscale score (as presented) is determined as per FACIT-f guidance, by multiplying the sum of the item scores by the number of items in the subscale, then divide by the number of items answered.

  5. Change in Quality Of Life Questionnaire (QOQ) Score at Days 0, 28, 90 and 180

    Time frame: Day 28, 90 and 180

    The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 instrument measures the change in the quality of of life of patients in the trial. It comprises 30 questions on daily QOL and incorporates a global health status, five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, nausea/vomiting, pain), and six single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). All of the scales range in score from 0 to 100, A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Scale scores were calculated by averaging items within scales and transforming average scores linearly.

  6. Dependency on Blood Transfusion

    Time frame: Day 0 through to study completion (2 years)

    Number of participants depending on blood transfusion prior to starting the study compared to during the study.

Sponsors and collaborators

Lead sponsor

AKARI Therapeutics

Industry

Collaborators

  • Radboud University Medical Center

Registry information

Official study title

Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Oct 30, 2015
Registry last updated
Jul 12, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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