Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)
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|ClinicalTrials.gov Identifier: NCT02591862|
Recruitment Status : Completed
First Posted : October 30, 2015
Last Update Posted : June 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Paroxysmal Nocturnal Haemoglobinuria (PNH)||Drug: Coversin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms|
|Actual Study Start Date :||February 2016|
|Actual Primary Completion Date :||February 2018|
|Actual Study Completion Date :||March 20, 2018|
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.
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
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02591862
|Dr Saskia Langemeijer|
|Nijmegen, Netherlands, 6525 GA|
|Principal Investigator:||Petra Dr Muus||Radboud University|
|Study Director:||Saskia Dr Langemeijer||Radboud University|