An Open Clincal Trial of Coversin in Patients with PNH

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-002067-33-GB
• Date of registration: 16/08/2016
• Prospective Registration: No
• Primary sponsor: Akari Therapeutics Plc
• Public title: An Open Clincal Trial of Coversin in Patients with PNH
• Scientific title: COBALT: Coversin Global Study: An Open-Label, Safety and Efficacy Trial in PNH Patients
• Date of first enrolment: 18/07/2016
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002067-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Akari Therapeutics Plc

• Name: Medical Director
• Affiliation: Akari Therapeutics Plc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with a diagnosis of PNH confirmed by flow cytometry who, in the opinion of the Investigator, would benefit from treatment with a complement C5 inhibitor
2. Aged 18 and above. No upper age limit
3. Males and females of childbearing potential must agree to use an adequate method of contraception. Females will have a negative pregnancy test before entry to the study
4. Body weight =50kg
5. The patient has given voluntary written informed consent
6. Willing to receive immunisation against Neisseria meningitidis and antibiotic prophylaxis in accordance with the local practice of the PI at the trial site. Antibiotic prophylaxis must continue until at least 14 days after the end of complement inhibition by Coversin.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Prior use of eculizumab (Soliris®) within 3 months of entry is prohibited
2. Any other drug acting directly on the complement system is prohibited
3. Chemotherapeutic agents within 3 months of enrolment in the study is prohibited
4. Tizanidine, if using ciprofloxacin prophylaxis is prohibited
5.Known sensitivity to the excipients of meningococcal vaccines, ciprofloxacin or any other antibiotic being administered for purposes of meningitis prophylaxis
6. Participation in other clinical trials within 4 weeks of signing the consent form
7. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
8. History of active systemic autoimmune diseases other than the target condition. Dermatologic diseases such as psoriasis will not be a reason for exclusion unless there are associated systemic symptoms such as arthritis
9. Any systemic disorder that could interfere with the evaluation of the study treatment (e.g. severe renal or hepatic disease that in the opinion of the Investigator would affect the outcome of the study or interfere with interpretation of results)
10. Failure to satisfy the investigator of fitness to participate for any other reason or any condition that, in the opinion of the Investigator, could increase the subject's risk by participating in the study or confound the outcome of the study




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Paroxysmal nocturnal haemoglobinuria (PNH)
MedDRA version: 20.0 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: Coversin
Product Code: rVA576
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: COVERSIN
Current Sponsor code: rVA576
Other descriptive name: COVERSIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Main Objective: The objectives of the study are:
• To assess the safety and tolerability of Coversin for all patients for the duration of the study.
• To assess efficacy of the dosage regimen to reduce haemolysis and control the signs and symptoms thereof, in PNH subjects as manifested by:
i. Serum lactic dehydrogenase (LDH) change from baseline (day 1) to day 28
ii. Haemoglobin (Hb) at day 28 and day 90, absolute and change from baseline
iii. Number of blood transfusions
iv. Quality of Life - EORTC QLQ-C30 at day 1 (baseline), 7, 14, 21, 29, 60 and 90 days
v. Quality of Life – EQ-5D-5L at baseline day 1 (baseline) up to day 60 and then at day 90.

• To determine whether self-injection by subjects with PNH is well-accepted and the home care nursing supervision period sufficient using a (non validated) questionnaire at day 29 and day 90.

Timepoint(s) of evaluation of this end point: Reduction in serum LDH measured on Days 1 (baseline) to Day 28.

Primary end point(s): Primary Efficacy Endpoint:
Reduction in serum LDH to less than or equal to 1.8 times the upper limit of normal (ULN) for the Investigator's reference laboratory or 500 I U/L
whichever is the lower from Day 1 (pre-dose) to Day 28

Secondary Objective: Not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: LDH measured from Day 1 (baseline) to Day 28.
Reduction in CH50 -Day 1, 7, 14, 21, 28, 60, 90.
HB-measured from Day 1 to Day 90.
EORTC QLQ C30 measured from Day 1 (baseline) to Days 7, 14, 21, 29,
60 and 90.
EQ-5D-5L measured from Day 1 (baseline) to Day 60 and then at Day 90.

AEs, SAEs, injection site reaction, lymph node inspection collected daily. Vital signs (blood pressure, body temperature and pulse) measured weekly from Day 0 to Day 90.
Change in weight or body fat measured at Day 1 and Day 90.

Secondary end point(s): Secondary Efficacy Endpoints:
• Reduction of LDH to Day 28 of 50% or less of the mean of all pre-dose measurements taken within 14 days of commencing Coversin treatment.
If only one result is available during that period it should be used.
• Reduction in CH50 from Day 1 pre-dose to Days 7, 14, 21, 28, 60 and 90
• Reduction in serum LDH to less than or equal to 1.8 times the upper limit of normal (ULN) for the Investigator’s reference laboratory or 500 I U/L whichever is the lower at Day 60 and at Day 90
• Increase in Hb Day 1 – Day 90
• Change in EORTC QLQ C30 score from Day 1 (baseline) to days 7, 14, 21, 29, 60 and 90
• Change in EQ-5D-5L from baseline Day 1 (baseline) to Day 60 and then at Day 90.


Safety Endpoints:
•Frequency, type and relationship of AEs and SAEs to treatment.
•Out of range laboratory parameters (haematology and chemistry).
•Vital signs (blood pressure, body temperature and pulse).
•ECG abnormalities pre dose – Day 90 (A resting pre-dose ECG taken within 7 days of first dose will be compared with ECGs taken 1- 6 hours post-dose and at 90 days of treatment with Coversin)
•Change in weight or percentage body fat will be noted pre-dose and at Day 90.
•Injection site reaction and lymph node inspection.
•Anti-coversin antibody production.

Secondary ID(s)

AK579

Source(s) of Monetary Support

Akari Therapeutics Plc

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 06/01/2019
• Date Completed: 21/12/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-002067-33/results