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Paroxysmal Nocturnal Haemoglobinuria (PNH)Phase 2NCT02591862

Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

A Phase 2 study testing Coversin in people with Paroxysmal Nocturnal Haemoglobinuria (PNH), run by AKARI Therapeutics at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Coversin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteNetherlands
Study dates
Feb 2016to 20 Mar 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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.

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Dr Saskia Langemeijer

    Nijmegen, 6525 GA

Other trials in Netherlands

About this study

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

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

Read the 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.

Being tested
Coversin
Medical subject headings
Hemoglobinuria, Paroxysmal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CoversinDrug

    Also called rVA576, rEV576

    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).

Study groups in NCT02591862
Study groupRoleWhat they receive
Coversin (Nomacopan)OtherThis is an open label, non-comparator study. Patient will be given a single ablating dose of 0.57mg/kg per subject followed by daily repeat maintenance doses. The initial repeat dose will be 25% of the ablating dose. If this is insufficient to maintain complement inhibition at ≤10% of baseline (pre-treatment) level after 5 days of treatment the daily dose will be increased by doubling until that level of inhibition is achieved. In the event of 100% inhibition being achieved the dose may be titrated downwards at the PI's discretion until a satisfactory clinical result is obtained. If at any point in treatment complement inhibition falls to less than 50% of baseline a further ablating dose of 0.57mg/kg should be given. Coversin lyophilised powder in each vial was diluted with 0.6 mL water for injection prior to use.
Receives: Drug: Coversin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Day 0 and Day 28

  2. Number and Type of Adverse Events (AE)

    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.

    Measured: 2 years

Secondary outcomes (6)

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

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

    Measured: Baseline, Day 28, Day 90 and Day 180

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

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

    Measured: Baseline, Day 28, Day 90 and Day 180

  3. Measurement of Lactate Dehydrogenase (LDH) at 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.

    Measured: Baseline, Day 90 and Day 180

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

    Measured: Day 28, 90 and 180

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

    Measured: Day 28, 90 and 180

  6. Dependency on Blood Transfusion

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

    Measured: Day 0 through to study completion (2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2015 (estimated)
  2. Study startFeb 2016
  3. Primary completion20 Mar 2018
  4. Study completion20 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02591862
Sponsor's protocol ID
AK578
Status last verified
Feb 2017
First submitted
10 Sep 2015
Last updated
12 Jul 2023
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31840801

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Coversin in people with Paroxysmal Nocturnal Haemoglobinuria (PNH), run by AKARI Therapeutics at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measurement of Ratio of LDH to the Upper Limit of Normal (ULN) (time frame: Day 0 and Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02591862, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2023.

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