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    Summary
    EudraCT Number:2017-005140-16
    Sponsor's Protocol Code Number:APL2-202
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-03-26
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2017-005140-16
    A.3Full title of the trial
    A Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects with Paroxysmal Nocturnal Hemoglobinuria (PNH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase IIa study of APL-2 in patients with PNH
    A.4.1Sponsor's protocol code numberAPL2-202
    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 SponsorApellis Pharmaceuticals
    B.1.3.4CountryUnited States
    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 supportApellis Pharmaceuticals
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationApellis Pharmaceuticals
    B.5.2Functional name of contact pointHead of Clinical Operations
    B.5.3 Address:
    B.5.3.1Street Address6400 Westwind Way, Suite A
    B.5.3.2Town/ cityCrestwood
    B.5.3.3Post codeKY 40014
    B.5.3.4CountryUnited States
    B.5.6E-mailclinicaltrials@apellis.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/3/17/1873
    D.3 Description of the IMP
    D.3.2Product code APL-2
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNNot yet assigned
    D.3.9.1CAS number 2019171-69-6
    D.3.9.2Current sponsor codeAPL-2
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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 Hemoglobinuria (PNH)
    E.1.1.1Medical condition in easily understood language
    Paroxysmal Nocturnal Hemoglobinuria (PNH)
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10055629
    E.1.2Term Paroxysmal nocturnal hemoglobinuria
    E.1.2System Organ Class 100000004857
    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 safety, tolerability, preliminary efficacy and PK of multiple SC doses of APL-2 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab (Soliris)® in the past.
    E.2.2Secondary objectives of the trial
    An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of APL-2 when administered to PNH subjects.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. At least 18 years old (inclusive)
    2. Diagnosed with PNH (WBC clone >10%)
    3. Lactose dehydrogenase ≥2 times the upper limit of normal
    4. Screening Ferritin ≥ normal and Total Iron Binding Capacity (TIBC) ≤ LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study (see Protocol Section 8.4.4)
    5. Last transfusion within 12 months prior to screening
    6. Platelet count of >30,000/mm3 at the screening visit
    7. Absolute neutrophil count >500/ mm3 at the screening visit
    8. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study
    9. Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
    10. Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
    11. Willing and able to give informed consent
    E.4Principal exclusion criteria
    1. Prior eculizumab (Soliris®) treatment
    2. Active bacterial infection
    3. Hereditary complement deficiency
    4. History of bone marrow transplantation
    5. Concurrent SAA, defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or antithymocyte globulin
    6. Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days
    7. Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening
    8. Breast-feeding women
    9. History of meningococcal disease
    E.5 End points
    E.5.1Primary end point(s)
    Primary Safety Endpoint:
    The primary safety endpoints of the study are the number and severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.

    Primary Efficacy Endpoints:
    • Change from baseline in Lactate dehydrogenase (LD)
    • Change from baseline in Haptoglobin
    • Change from baseline in Hemoglobin (Hb)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary Safety Endpoint:
    after dosing on Day 1 and up to 30 days after the last dose of study medication.
    Primary Efficacy Endpoints:
    Change from baseline in LD, Haptoglobin and Hb: will be calculated for each post dose assessment. The baseline: the last measurement prior to the start of dosing. Please refer to STUDY FLOW CHART in the Protocol.
    E.5.2Secondary end point(s)
    • APL-2 plasma concentrations (and pharmacokinetic (PK) parameters as appropriate)
    • Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale score
    • Change from baseline in reticulocyte count
    • Change from baseline in total bilirubin
    • Number of red blood cell (RBC) transfusions per month
    • Change from baseline in Linear Analog Scale Assessment (LASA) for Quality of Life
    Baseline will be taken as the last measurement prior to the start of dosing.
    For transfusions baseline will be taken from the 12 month transfusion history.

    Exploratory PD markers include:
    • Complement (CH50, AP50, and C3) levels
    • C3 deposition on RBC cells
    • Clonal distribution of PNH RBCs

    E.5.2.1Timepoint(s) of evaluation of this end point
    • APL-2 plasma concentrations (and PK parameters): Plasma concentrations of APL-2 will be determined from multiple samples taken between Day 1 and the Exit Visit.
    • Change from baseline in FACIT Fatigue Scale score: Please refer to STUDY FLOW CHART in the Protocol
    • Change from baseline in reticulocyte count: Please refer to STUDY FLOW CHART in the Protocol
    • Change from baseline in total bilirubin: Please refer to STUDY FLOW CHART in the Protocol
    • Number of RBC transfusions per month: Please refer to STUDY FLOW CHART in the Protocol
    • Change from baseline in Linear Analog Scale Assessment for Quality of Life: Please refer to STUDY FLOW CHART in the Protocol
    Baseline: the last measurement prior to the start of dosing.
    Baseline for transfusions: from the 12 M transfusion history
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 Yes
    E.8.1.7.1Other trial design description
    Intra-subject dose escalation up to a dose of 360 mg/day (from Part 2A)
    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.8.2.4Number of treatment arms in the trial1
    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 EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Bulgaria
    Greece
    Poland
    Romania
    Serbia
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months7
    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: 16
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 17
    F.4.2.2In the whole clinical trial 20
    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)
    None. Expected normal treatment of the condition.
    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 Decision2018-07-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-05-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-10-22
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