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    Summary
    EudraCT Number:2021-003704-40
    Sponsor's Protocol Code Number:ISIS702843-CS4
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-12-20
    Trial 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 number2021-003704-40
    A.3Full title of the trial
    A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients with Phlebotomy Dependent Polycythemia Vera (PD-PV)
    A.4.1Sponsor's protocol code numberISIS702843-CS4
    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 SponsorIonis 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 supportIonis Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIonis Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointLynne Baron
    B.5.3 Address:
    B.5.3.1Street Address2855 Gazelle Court
    B.5.3.2Town/ cityCarlsbad, CA
    B.5.3.3Post code92010
    B.5.3.4CountryUnited States
    B.5.4Telephone number0017606032797
    B.5.6E-maillbaron@ionisph.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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameISIS 702843
    D.3.2Product code ISIS 702843
    D.3.4Pharmaceutical form Injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInjection (Noncurrent)
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSapablursen
    D.3.9.1CAS number 2273007-95-5
    D.3.9.2Current sponsor codeISIS 702843
    D.3.9.3Other descriptive nameIONIS TMPRSS6-LRx
    D.3.9.4EV Substance CodeSUB199752
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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
    Polycythemia Vera
    E.1.1.1Medical condition in easily understood language
    Medical condition in which the bone marrow makes too many red blood cells.
    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 21.1
    E.1.2Level LLT
    E.1.2Classification code 10036061
    E.1.2Term Polycythemia vera
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Evaluate the efficacy of ISIS 702843 to reduce the frequency of phlebotomy throughout the last 20 weeks of the Treatment Period
    E.2.2Secondary objectives of the trial
    1) Evaluate the efficacy of ISIS 702843 to decrease the frequency of phlebotomy by various thresholds throughout the last 20 weeks of the Treatment Period
    2) Evaluate the efficacy of ISIS 702843 to improve the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score (TSS) at Week 37
    Safety Objective
    1) Evaluate the safety and tolerability of multiple doses of ISIS 702843 i patients with PD-PV through Week 73
    Exploratory Objectives
    1) Evaluate the efficacy of ISIS 702843 to control Hct without phlebotomy throughout the last 20 weeks of the Treatment Period
    2) Evaluate the efficacy of ISIS 702843 to reduce the frequency of phlebotomy from Week 37 to 73 of the Treatment Extension Period
    3) Evaluate the efficacy of ISIS 702843 to control Hct without phlebotomy from Week 37 to 73 of the Treatment Extension Period
    PK Objectives
    1) Evaluate PK exposure over time and potential PK/PD correlation on relevant biomarkers and efficacy outcome measures
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Meet modified World Health Organization (WHO) 2016 diagnostic criteria for polycythemia vera (PV) at the time of clinical diagnosis
    2. Participant must be phlebotomy dependent
    3. Patients do not need to be on cytoreductive therapy and do not need to have been previously treated with cytoreductive therapy. If the patient was previously treated with the cytoreductive therapy it must have been discontinued at least 3 months prior to Screening. If patients are currently on cytoreductive therapy they must be on a stable dose for at least 3 months prior to Screening.
    E.4Principal exclusion criteria
    1. Meets criteria for post-polycythemia vera myelofibrosis (PPV-MF) as defined by the International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
    2. Moderate to severe splenic pain or spleen-related organ obstruction
    3. Active or chronic bleeding within 1 month of Screening, significant concurrent/recent coagulopathy, history of immune thrombocytopenic purpura (ITP)
    4. Known primary or secondary immunodeficiency
    5. Active infection with human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
    6. Active infection requiring systemic antiviral or antimicrobial therapy or active novel coronavirus disease (Covid-19) infection
    7. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or non-metastatic prostate cancer that has been successfully treated
    8. Surgery requiring general anesthesia within 1 month prior to Screening
    E.5 End points
    E.5.1Primary end point(s)
    Reduction in the frequency of phlebotomy comparing Baseline with the last 20 weeks of the 37-week Treatment Period
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 17 to Week 37
    E.5.2Secondary end point(s)
    1) Proportion of patients achieving a reduction in the frequency of phlebotomy by ≥ 30%, ≥ 50%, ≥ 75% and ≥ 90% comparing Baseline with the last 20 weeks of the 37-week Treatment Period [ Time Frame: Week 17 to Week 37 ]
    2) Change in the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF-TSS) From Baseline to Week 37 [ Time Frame: Baseline up to Week 37 ]
    Safety Endpoint
    1) AEs, vital signs, clinical laboratory tests (serum chemistry, hematology, urinalysis, coagulation panel, thyroid panel [TSH, T3, T4], electrocardiogram [ECG]
    Exploratory Endpoints:
    1) Proportion of patients achieving Hct control (i.e. Hct<45%) without receiving phlebotomy throughout the last 20 weeks of the 37-week Treatment Period
    2) Reduction in the frequency of phlebotomy comparing Baseline to the last 36 Weeks of the Treatment Extension Period
    3) Propotion of patients achieving Hct control (i.e., Hct<45%) without receiving phlebotomy from Week 37 to 73 of the Treatment Extension Period
    PK Endpoint
    1) A PK profile including pre-dose, 1,2,4, and optional 6-hour samples will be collected at Day 1. A PK profile will also be collected at Week 25 and will include: pre-dose, 1-, 2-, and 3-hour samples. Trough levels will be evaluated at all clinic visits at will not be required for hom health care visits.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Week 17 to week 37
    2) From Baseline to week 37
    Safety Endpoint
    1) From Baseline to week 73
    Exploratory Endpoint
    1) From Baseline to week 37
    2) From week 37 to week 73
    3) From week 37 to week 73
    PK Endpoint
    1) Day 1 and Week 25
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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 Yes
    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.8.2.4Number 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    Australia
    Canada
    United Kingdom
    United States
    Poland
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days18
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days18
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 10
    F.4.2.2In the whole clinical trial 60
    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)
    Patients who discontinue from treatment early will complete an ETT visit and be encouraged to continue follow up in the Post-Treatment Period.
    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 Decision2023-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-12-06
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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