Clinical Trial: Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 Summary: 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.
Sponsor: AKARI Therapeutics

Current Primary Outcome: 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: Same as current

Current Secondary Outcome:

  • 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: Same as current

Information By: AKARI Therapeutics

Dates:
Date Received: September 10, 2015
Date Started: February 2016
Date Completion: December 2018
Last Updated: January 23, 2017
Last Verified: January 2017