Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH)

NCT02591862 | Completed Phase 2 Results DMC

• 1 other identifier: AK578
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Coversin in Paroxysmal Nocturnal Haemoglobinuria (PNH) in patients with resistance to Eculizumab due to complement C5 polymorphisms.

Conditions

Paroxysmal Nocturnal Haemoglobinuria (PNH)

Outcome Measures

Primary Outcomes (2)

• Measurement of Ratio of LDH to the Upper Limit of Normal (ULN)

  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. Units are measured in ratio of LDH:ULN, where the ULN is 250 U/L. The primary efficacy endpoint was the LDH AUC from Day 0 to 28 compared with 28 days pretreatment. Data for the 28 days pre-treatment was not collected, and as only one patient was recruited, the LDH values compared with baseline and the ratio of LDH to the Upper Limit of Normal (ULN) are presented.

  Day 0 and Day 28

• Number and Type of Adverse Events (AE)

  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.

  2 years

Secondary Outcomes (6)

• Measurement of Haemoglobin (Hb) at Days 28, 90, and 180, Absolute and Change From Baseline

  Baseline, Day 28, Day 90 and Day 180

• Measurement of Haptoglobin (Hp) at Days 28, 90 and 180, Absolute and Change From Baseline

  Baseline, Day 28, Day 90 and Day 180

• Measurement of Lactate Dehydrogenase (LDH) at Baseline, Day 90 and Day 180

  Baseline, Day 90 and Day 180

• Change in Functional Assessment of Chronic Illness Therapy (FACIT) Score at Days 0, 28, 90 and 180

  Day 28, 90 and 180

• Change in Quality Of Life Questionnaire (QOQ) Score at Days 0, 28, 90 and 180

  Day 28, 90 and 180

Study Arms (1)

Coversin (Nomacopan)

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

Drug: Coversin

Interventions

Coversin 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).

Also known as: rVA576, rEV576

Coversin (Nomacopan)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• AKARI Therapeutics: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Dr Saskia Langemeijer

Nijmegen, 6525 GA, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 31840801 RESULT

Related Links

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

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

rEV576 protein, tick

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Akari Therapeutics plc

miles.nunn@akaritx.com

02080040261

Study Officials

• Petra Dr Muus

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Saskia Dr Langemeijer

  Radboud University Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: October 30, 2015
• Study Start: February 1, 2016
• Primary Completion: March 20, 2018
• Study Completion: March 20, 2018
• Last Updated: July 12, 2023
• Results First Posted: July 12, 2023

Record last verified: 2017-02

Locations

NL (1)