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    Summary
    EudraCT Number:2016-002067-33
    Sponsor's Protocol Code Number:AK579
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-08-16
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2016-002067-33
    A.3Full title of the trial
    COBALT: Coversin Global Study: An Open-Label, Safety and Efficacy Trial in PNH Patients
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    An Open Clincal Trial of Coversin in Patients with PNH
    A.4.1Sponsor's protocol code numberAK579
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAkari Therapeutics Plc
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAkari Therapeutics Plc
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAkari Therapeutics Plc
    B.5.2Functional name of contact pointMedical Director
    B.5.3 Address:
    B.5.3.1Street Address75-76 Wimpole Stree
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeW1G 9RT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+440208004 0261
    B.5.6E-mailwwd@akaritx.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1725
    D.3 Description of the IMP
    D.3.1Product nameCoversin
    D.3.2Product code rVA576
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCOVERSIN
    D.3.9.2Current sponsor coderVA576
    D.3.9.3Other descriptive nameCOVERSIN
    D.3.9.4EV Substance CodeSUB182098
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number18
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Paroxysmal nocturnal haemoglobinuria (PNH)
    E.1.1.1Medical condition in easily understood language
    Paroxysmal nocturnal haemoglobinuria (PNH)
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10034042
    E.1.2Term Paroxysmal nocturnal haemoglobinuria
    E.1.2System Organ Class 10038359 - Renal and urinary disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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.
    E.2.2Secondary objectives of the trial
    Not applicable
    E.2.3Trial contains a sub-study No
    E.3Principal 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.
    E.4Principal 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

    E.5 End points
    E.5.1Primary 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
    E.5.1.1Timepoint(s) of evaluation of this end point
    Reduction in serum LDH measured on Days 1 (baseline) to Day 28.
    E.5.2Secondary 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.
    E.5.2.1Timepoint(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.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LSLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months14
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months15
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 9
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 10
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Enrollment onto a long-term safety maintenance study with Coversin or alternative standard of care treatment.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-07-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-12-21
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