Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

NCT ID: NCT02591862

Last Updated: 2023-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2018-03-20

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 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.

Conditions

Paroxysmal Nocturnal Haemoglobinuria (PNH)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Coversin (Nomacopan)

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. Coversin lyophilised powder in each vial was diluted with 0.6 mL water for injection prior to use.

Group Type: OTHER

Coversin

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

rVA576; rEV576

Eligibility 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 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
• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

AKARI Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petra Dr Muus

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Saskia Dr Langemeijer

Role: STUDY_DIRECTOR

Radboud University Medical Center

Locations

Dr Saskia Langemeijer

Nijmegen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: RESULT

PMID: 31840801 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/31840801/

Successful treatment of a PNH patient non-responsive to eculizumab with the novel complement C5 inhibitor coversin (nomacopan)

Other Identifiers

AK578

Identifier Type: -

Identifier Source: org_study_id