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    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2018-004220-11
    Sponsor's Protocol Code Number:APL2-308
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-05-13
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2018-004220-11
    A.3Full title of the trial
    A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
    Randomizowane, wieloośrodkowe, prowadzone metodą otwartej próby, kontrolowane badanie fazy 3 mające na celu ocenę skuteczności i bezpieczeństwa APL-2 u pacjentów z napadową hemoglobinurią nocną (PNH)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Research Study to Gather Scientific Information About the Efficacy and Safety of the Investigational Drug APL-2 In Treating Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH), a Disease Associated with Anemia, In a Randomly Assigned Comparison with the Current Standard of Care Treatment Approved for PNH
    A.3.2Name or abbreviated title of the trial where available
    PRINCE
    A.4.1Sponsor's protocol code numberAPL2-308
    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, Inc.
    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, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationArgint International Clinical Research & Development Services Kft.
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressBölöni György u. 22.
    B.5.3.2Town/ cityBudapest
    B.5.3.3Post code1021
    B.5.3.4CountryHungary
    B.5.6E-mailclinicaltrials@argintinternational.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.3.1Product nameAPL-2
    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 INNpegcetacoplan
    D.3.9.1CAS number 2019171-69-6
    D.3.9.2Current sponsor codeAPL-2
    D.3.9.3Other descriptive nameAPL-2
    D.3.9.4EV Substance CodeSUB192794
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number54
    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
    PNH is a rare disorder causing red blood cells to break down too early.
    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 primary objective of this study is to evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), in patients with PNH, as assessed by:
    • Hemoglobin stabilization defined as avoidance of a > 1 g/dl decrease in Hb levels from Baseline in the absence of transfusion through Week 26 (Yes/No)
    AND
    • Reduction in lactate dehydrogenase (LDH) level from Baseline to Week 26
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), as assessed by:
    o Hemoglobin response in the absence of transfusions (Hb response defined as a ≥1g/dL increase in Hb from Baseline at Week 26)
    o Change from Baseline to Week 26 (W 26) in absolute reticulocyte count
    o Change from Baseline to W 26 in Hb level
    o Number of PRBC units transfused from Baseline to W 26
    o Change from Baseline to W 26 in FACIT- Fatigue Scale score
    o Normalization of Hb levels (≥1x ULN) from Baseline at W 26 in the absence of transfusions
    o Normalization of LDH levels of ≤1 x the upper limit of normal from Week 4 to W 26 in the absence of transfusions
    o Change from Baseline to W 26 in EORTC QLQ-C30 scores
    o Change from Baseline to W 26 in LASA scale scores
    o Change from Baseline to W 26 in LDH level
    o Absolute reticulocyte count normalization (<1 x ULN) at W 26
    o Time of failure of Hb stabilization
    o Time to transfusion

    • To evaluate the safety of APL-2
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    At Visit 1 screening, subjects must fulfill all of the following inclusion criteria to be eligible for participation in the study:
    1. Be at least 18 years old (inclusive).
    2. Have LDH ≥1.5 x ULN at the screening visit.
    3. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%).
    4. Have Hb less than the lower limit of normal (LLN) at the screening visit.
    5. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject’s dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study.
    6. Body mass index (BMI) ≤ 35 kg/m2 at the screening visit.
    7. Have a platelet count of >50,000/mm3 at the screening visit.
    8. Have an absolute neutrophil count >500/mm3 at the screening visit.
    9. 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 and for 90 days after their last dose of study drug.
    10. Males must agree to use protocol-defined methods of contraception and agree to refrain from donating sperm for the duration of the study and for 90 days after their last dose of study drug.
    11. Have vaccination against Streptococcus pneumoniae, Neisseria meningitides (types A, C, W, Y, and B), and Haemophilus influenzae (type B) either within 2 years prior to Day 1 dosing, or agree to receive vaccination 14 days after starting treatment with APL-2 (along with prophylactic antibiotic therapy for at least the 14 days between APL-2 treatment initiation and vaccination and for 14 days post vaccination). Vaccination is mandatory, unless documented evidence exists that subjects are non-responders to vaccination (as evidenced by titers or display titer levels within acceptable local limits).
    12. Be willing and able to give informed consent.
    E.4Principal exclusion criteria
    Subjects will be excluded from the study if there is evidence of any of the following criteria at screening:
    1. Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening.
    2. Hereditary complement deficiency.
    3. History of bone marrow transplantation.
    4. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening:
    • Erythropoietin or immunosuppressants for at least 8 weeks
    • Systemic corticosteroids for at least 4 weeks
    • Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks
    • Iron supplements, vitamin B12, or folic acid for at least 4 weeks
    • Low-molecular-weight heparin for at least 4 weeks
    5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration.
    6. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or 5 half-lives, whichever is longer.
    7. Planning to become pregnant or currently a breast-feeding woman.
    8. History of meningococcal disease.
    9. Any comorbidity or condition (such as malignancy) that, in the opinion of the Investigator, could put the subject at increased risk or potentially confound study data.
    E.5 End points
    E.5.1Primary end point(s)
    Hemoglobin stabilization defined as avoidance of a > 1 g/dl decrease in Hb levels from Baseline in the absence of transfusion through Week 26 (Yes/No)
    AND
    Reduction in lactate dehydrogenase (LDH) level from Baseline to Week 26
    E.5.1.1Timepoint(s) of evaluation of this end point
    from Baseline through Week 26
    E.5.2Secondary end point(s)
    Efficacy end points:
    o Hemoglobin response (Yes/No) in the absence of transfusions (Hb response is defined as a ≥1g/dL increase in Hb from Baseline at Week 26)
    o Change from Baseline to Week 26 in absolute reticulocyte count
    o Change from Baseline to Week 26 in Hb level
    o Number of packed red blood cell (PRBC) units transfused from Baseline to Week 26
    o Change from Baseline to Week 26 in Functional Assessment of Chronic Illness Therapy- (FACIT-) Fatigue Scale score
    o Normalization of Hb levels (defined as ≥1x ULN) from Baseline at Week 26 in the absence of transfusions (Yes/No)
    o Normalization of LDH levels of ≤1 x the upper limit of normal (ULN) from Week 4 to Week 26 in the absence of transfusions (Yes/No)
    o Change from Baseline to Week 26 in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ C30) scores (Version 3)
    o Change from Baseline to Week 26 in Linear Analog Assessment (LASA) scale scores
    o Change from Baseline to Week 26 in LDH level
    o Absolute reticulocyte count normalization (<1 x ULN) at Week 26 (Yes/No)
    o Time of failure of Hb stabilization
    o Time to transfusion

    Safety end points:
    o Incidence and severity of treatment-emergent adverse events (TEAEs)
    o Incidence of thromboembolic events
    o Changes from Baseline in laboratory parameters
    o Changes from Baseline in ECG parameters
    o Incidence of anti-APL2 antibodies
    E.5.2.1Timepoint(s) of evaluation of this end point
    from Baseline to Week 26
    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 No
    E.6.10Pharmacogenetic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3.1Comparator description
    Standard of Care (Excluding Complement Inhibitors)
    E.8.2.4Number of treatment arms in the trial2
    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 concerned3
    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 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
    Argentina
    Brazil
    Colombia
    Hong Kong
    Hungary
    Malaysia
    Mexico
    Peru
    Philippines
    Poland
    Serbia
    Thailand
    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 months6
    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 months6
    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: 27
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 27
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 22
    F.4.2.2In the whole clinical trial 54
    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)
    Following the completion of the Randomized-Controlled Period, subjects may be offered entry into a separate open-label, long-term extension study in order to continue to receive treatment with APL-2.
    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 Decision2019-07-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-06-23
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