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    Summary
    EudraCT Number:2021-006390-37
    Sponsor's Protocol Code Number:VX21-CTX001-161
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2022-03-08
    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 ConcernedGermany - PEI
    A.2EudraCT number2021-006390-37
    A.3Full title of the trial
    A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects with Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to learn about the safety and efficacy of CTX001 (the "study drug product") to treat beta-thalassemia and severe sickle cell disease in patients
    A.4.1Sponsor's protocol code numberVX21-CTX001-161
    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 SponsorVertex Pharmaceuticals Incorporated
    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 supportVertex Pharmaceuticals Incorporated
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVertex Pharmaceuticals Incorporated
    B.5.2Functional name of contact pointClinical Trials and Medical Info
    B.5.3 Address:
    B.5.3.1Street Address50 Northern Avenue
    B.5.3.2Town/ cityBoston
    B.5.3.3Post codeMA 02210
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1877 634 8789
    B.5.6E-mailmedicalinfo@vrtx.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 numberSCD: EU/3/19/2242, TDT: EU/3/19/2210
    D.3 Description of the IMP
    D.3.1Product nameExagamglogene autotemcel (Exa-cel)
    D.3.2Product code CTX001
    D.3.4Pharmaceutical form Dispersion for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAutologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs)
    D.3.9.2Current sponsor codeCTX001
    D.3.9.3Other descriptive nameCTX001
    D.3.9.4EV Substance CodeSUB192451
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number3
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    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 Yes
    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
    Transfusion-dependent β-thalassemia (TDT) and severe sickle cell disease (SCD)
    E.1.1.1Medical condition in easily understood language
    Transfusion-dependent β-thalassemia and severe sickle cell disease
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10040641
    E.1.2Term Sickle cell anaemia
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10054660
    E.1.2Term Thalassemia beta
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess HbF levels over time, after a single dose of autologous CRISPR/Cas9
    modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs)
    (CTX001) in adolescent and adult subjects with either Transfusion-dependent
    β-Thalassemia (TDT) or severe sickle cell disease (SCD)
    E.2.2Secondary objectives of the trial
    • To evaluate efficacy and safety of a single dose of CTX001 in adolescent and
    adult subjects with either TDT or severe SCD
    • Assess the effects of infusion of CTX001 on disease-specific events and
    clinical status
    • Quantify gene editing efficiency
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects with TDT:
    • Subjects 12 to 35 years of age, inclusive, on the date of informed consent
    • Eligible for autologous stem cell transplant as per investigator’s judgement
    • Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by:
    • Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Subjects can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning.
    • A history of at least 100mL/kg/year or 10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening

    Subjects with SCD:
    • Subjects 12 to 35 years of age, inclusive, on the date of informed consent
    • Documented βS/βS, βS/β0, or βS/β+, subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning
    • Eligible for autologous stem cell transplant as per investigator’s judgment
    • Subjects with severe SCD. Severe SCD defined aby the occurrence of at least 2 of the following events per year during the 2-year period before screening, while receiving appropriate supportive care (e.g. pain management plan, HU):
    • Acute pain events that require a visit to a medical facility and administration of pain medications (opioids or intravenous [IV] non-steroidal anti-inflammatory drugs [NSAIDs]) or RBC transfusions
    • Acute chest syndrome, as indicated by the presence of a new pulmonary infiltrate associated with pneumonia-like symptoms, pain, or fever
    • Priapism lasting >2 hours and requiring a visit to a medical facility
    • Splenic sequestration, as defined by an enlarged spleen, left upper quadrant pain, and an acute decrease in hemoglobin concentration of ≥2 g/dL.

    Other protocol defined inclusion criteria may apply
    E.4Principal exclusion criteria
    Subjects with TDT:
    • A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is
    • available per investigator’s judgement.
    • Prior hematopoietic stem cell transplant (HSCT).
    • Subjects with associated α-thalassemia and >1 alpha deletion, or alpha multiplications.
    • Subjects with sickle cell β-thalassemia variant.
    • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
    • White blood cell (WBC) count <3 × 109/L or platelet count <50 × 109/L not related to hypersplenism per investigator judgment.

    Subjects with SCD:
    • A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator’s judgement.
    • Prior hematopoietic stem cell transplant (HSCT).
    • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.

    Other protocol defined exclusion criteria may apply
    E.5 End points
    E.5.1Primary end point(s)
    HbF and Hb levels over time. The evaluation will start 60 days after last RBC
    transfusion for post-transplant support or disease management.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 12 months
    E.5.2Secondary end point(s)
    TDT or SCD:
    • Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality.
    • Relative reduction from baseline in annualized volume of RBC
    • Proportion of alleles with intended genetic modification present in peripheral blood over time
    • Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time

    TDT only:
    • Duration transfusion free

    SCD only:
    • Relative reduction from baseline in annualized rate of severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management.
    • Relative reduction from baseline in rate of inpatient hospitalizations for severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management.
    • Relative change from baseline in annualized duration of hospitalization for severe VOCs up to 12 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
    • Relative reduction from baseline in markers of hemolysis up to 12 months after CTX001 infusion.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to 12 months
    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 No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    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
    Saudi Arabia
    United States
    Germany
    Italy
    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
    The end of study is defined as the last scheduled visit (or contact) of the last subject, which is the date the last subject completes the 24- month follow up period or date of early withdrawal from the study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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 Yes
    F.1.1Number of subjects for this age range: 11
    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) Yes
    F.1.1.6.1Number of subjects for this age range: 11
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 7
    F.1.3Elderly (>=65 years) No
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 26
    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)
    All subjects infused with CTX001 will be asked either to enroll in a long term follow-up study (Study VX-CTX001-131) or registry study (if available), for 15 years total follow up post-CTX001 infusion.
    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 Decision2022-08-29
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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