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Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02591862
Recruitment Status : Completed
First Posted : October 30, 2015
Last Update Posted : June 4, 2018
Radboud University
Information provided by (Responsible Party):
AKARI Therapeutics

Tracking Information
First Submitted Date  ICMJE September 10, 2015
First Posted Date  ICMJE October 30, 2015
Last Update Posted Date June 4, 2018
Actual Study Start Date  ICMJE February 2016
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
Measurement of Serum Lactic Dehydrogenase (LDH) from Day 0 (pre-dose) to Day 28 (AUC) compared with 28 days pre-treatment [ Time Frame: Day 0 to 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. Serum LDH less than 100% above Upper Limit Of Normal Total (ULNt) 28 days
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
  • Measurement of Haemoglobin (Hb) [ Time Frame: Day 28 and Day 180 ]
    Measuring change in mean Hb from Day 28 and Day 180 (absolute and change from baseline)
  • Measurement of Haptoglobin (Hp) [ Time Frame: Day 28 and Day 180 ]
    Measuring change in mean Hp from Day 28 - Day 180 (absolute and change from baseline)
  • Measurement of Change in LDH [ Time Frame: Day 0 (pre-dose) at monthly intervals up to 1 year ]
    Measuring the change in LDH from Day 0 (pre-dose) and at 24 hrs (pre-dose) 48 hrs (pre-dose) Day 2 Day 5 Day 7,14 and 21 Day 28, 35, 42, 49 Day 60 (weeks 8, 10 and 12) Day 90 (weeks 14, 16, 18, 20 and month 5) Day 180 (months 6, 7, 8, 9, 10 and 11) 1 year (month 12, and every 3 months) End of study
  • Change in proportion of PNH [ Time Frame: Day 0 - Day 90 ]
    Measuring the change in proportion of PNH Type III red cells from Day 0 - Day 90
  • Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score [ Time Frame: Day 0 - Day 180 ]
    Measuring the change in FACIT score from Day 0 - to Day 180. This validation instrument will be used to measure: Patient well-being Physical well-being Social/Family well-being Functional well-being
  • Change in Quality Of Life Questionnaire (QOQ) Score [ Time Frame: Day 0 - Day 180 ]
    Measuring the change in patients quality of life using the European Organization for Research and Treatment of Cancer (EORTC) QOQ C30 instrument. This will assess the quality of of life of patients on this trial.
  • Number and type of adverse events (AE) [ Time Frame: 6 months ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)
Official Title  ICMJE Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Haemoglobinuria (PNH)
Intervention  ICMJE Drug: Coversin
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 Name: rVA576
Study Arms  ICMJE Coversin

This 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.

Intervention: Drug: Coversin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 29, 2015)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 20, 2018
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 5mug/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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02591862
Other Study ID Numbers  ICMJE AK578
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AKARI Therapeutics
Study Sponsor  ICMJE AKARI Therapeutics
Collaborators  ICMJE Radboud University
Investigators  ICMJE
Principal Investigator: Petra Dr Muus Radboud University
Study Director: Saskia Dr Langemeijer Radboud University
PRS Account AKARI Therapeutics
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP