Title

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

    Phase 2
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Intervention/Treatment

    coversin ...
  • Study Participants

    6
Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.
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 Started
Feb 29
2016
Primary Completion
Feb 28
2018
Study Completion
Mar 20
2018
Last Update
Jun 04
2018

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 names: rVA576

Coversin Other

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.

Criteria

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)
No Results Posted