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    Summary
    EudraCT Number:2018-001320-19
    Sponsor's Protocol Code Number:CTX001-121
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-01-25
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-001320-19
    A.3Full title of the trial
    A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Severe Sickle Cell Disease
    Studio di fase 1/2 per valutare la sicurezza e l’efficacia di una dose singola di cellule staminali ematopoietiche e progenitrici umane autologhe, CD34+, modificate con CRISPR-Cas9 (CTX001) in soggetti affetti da malattia a cellule falciformi grave
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study conducted to learn more about the safety and effects of CTX001 (the “Study Therapy”) in patients with Severe Sickle Cell Disease
    Studio condotto per apprendere maggiori informazioni circa la sicurezza e gli effetti di CTX001 (la “Terapia dello Studio”) in pazienti affetti da una forma grave di malattia a cellule falciformi
    A.3.2Name or abbreviated title of the trial where available
    A study to learn about the safety and efficacy of CTX001 (the "study drug") for the treatment of sev
    Uno studio per conoscere la sicurezza e l'efficacia di CTX001 (il "farmaco in studio") per il tratta
    A.4.1Sponsor's protocol code numberCTX001-121
    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 number0018776348789
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCTX001
    D.3.2Product code [CTX001]
    D.3.4Pharmaceutical form Solution 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 INNcellule ematopoietiche staminali e progenitrici umane (hHSPCs) autologhe, CD34+, modificate con CRISPR-Cas9
    D.3.9.2Current sponsor codeCTX001
    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 Yes
    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 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
    Sickle Cell Disease
    anemia falciforme grave
    E.1.1.1Medical condition in easily understood language
    Sickle Cell Disease
    anemia falciforme grave
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10043391
    E.1.2Term Thalassaemia 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
    tEvaluate the safety and efficacy of a single dose of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in subjects with severe sickle cell disease (SCD)
    Valutare la sicurezza e l'efficacia di una singola dose di cellule staminali ematopoietiche e cellule progenitrici umane (Human Hematopoietic Stem and Progenitor Cells, hHSPCs) CD34+ autologhe modificate mediante CRISPR-Cas9 (CTX001) in soggetti con anemia falciforme grave (Sickle Cell Disease, SCD)
    E.2.2Secondary objectives of the trial
    -Assess the effects of infusion of CTX001 on disease-specific events and clinical status
    -Quantify gene editing efficiency
    - Valutare gli effetti dell'infusione di CTX001 su eventi specifici della malattia e sullo stato clinico
    - Quantificare l'efficienza dell'editing genetico
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject will sign and date an informed consent form (ICF).
    2. Subjects 18 to 35 years of age, inclusive on the date of informed consent.
    3. Documented ßS/ßS genotype or ßS/ß0. Subjects can be enrolled based on historical genotype results, but confirmation of genotype is required before busulfan conditioning.The ß0 genotypes are defined
    using the HbVar Database.
    Protocol CTX001-121, Version 2.0 Page 35 of 82
    CRISPR Therapeutics AG Confidential Information
    4. Subjects with severe SCD. Severe SCD is defined by 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) as judged by the investigator:
    • Acute pain events that requires 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 by 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. Historical severe VOCs will be adjudicated by the Endpoint Adjudication
    Committee (EAC).
    5. Karnofsky performance status of =80%.
    6. Eligible for autologous stem cell transplant as per investigator’s judgment.
    7. Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least 1 ovary, and is less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from consent through at least 6 months after CTX001 infusion.
    8. Male subjects must agree to use effective contraception from start of mobilization through at least 6 months after CTX001 infusion
    9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.
    10. Willing to participate in an additional long-term follow-up study (Study VX18-CTX001-131) after completion of this study.
    1. In grado di fornire il consenso informato scritto.
    2. Età =18 e =35 anni, inclusa la data di firma del consenso informato scritto.
    3. Genotipo ßS/ßS o ßS/ß0 documentato. I soggetti possono essere aruolati in base ai risultati storici del genotipo, ma è richiesta la conferma del genotipo prima del condizionamento con busulfan. I genotipi ß0 sono definiti utilizzando il Dabase HbVar.
    4. Soggetti con SCD grave. Per "SCD grave" si intende il verificarsi, ogni anno durante i 2 anni antecedenti lo Screening e mentre si ricevono cure di supporto adeguate (ad es., piano di gestione del dolore, HU se indicato, ecc.), in base al giudizio dello Sperimentatore, di almeno 2 degli eventi seguenti:
    • Evento di dolore acuto per cui sia stata necessaria una visita presso una struttura medica e la somministrazione di farmaci antidolorifici (oppioidi o farmaci antinfiammatori non steroidei (FANS) per via endovenosa (EV)) oppure trasfusioni di eritrociti
    • Sindrome toracica acuta, che si evince dalla presenza di un nuovo infiltrato polmonare associato a sintomi simili a quelli della polmonite, dolore o febbre
    • Priapismo della durata> 2 ore
    • Sequestro splenico
    5. Performance Status Karnofsky di =80%.
    6. Idonei per il trapianto di cellule staminali autologhe in base al giudizio dello sperimentatore.
    7. I soggetti di sesso femminile in età fertile (dopo il menarca, con utero intatto e almeno 1 ovaio, e meno di 1 anno in post menopausa) devono acconsentire ad usare metodi contraccettivi accettabili dal consenso fino ad almeno 6 mesi dopo l’infusione di CTX001.
    8. I soggetti di sesso maschile devono acconsentire ad usare una contraccezione efficace (compresi i profilattici) dall’inizio del condizionamento con busulfan fino ad almeno 6 mesi dopo l’infusione di CTX001.
    9. Disposti e in grado di rispettare le visite programmate, il piano di trattamento, test di laboratorio, linee guida contraccettive e altre procedure di studio.
    10. Soggetti che acconsentono a partecipare ad uno studio o registro aggiuntivo di follow-up a lungo termine dopo il completamento di questo studio.
    E.4Principal exclusion criteria
    1. An available 10/10 human leukocyte antigen (HLA)-matched related donor.
    2. Prior HSCT.
    3. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
    4. White blood cell (WBC) count <3 × 109/L or platelet count <50 × 109/L, not related to hypersplenism per investigator judgment.
    5. Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.
    6. Subjects with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.
    7. More than 10 unplanned hospitalizations or emergency department visits related to SCD in the 1 year before screening that, in the opinion of the investigator, are consistent with significant chronic pain rather than acute pain crises.
    8. HbF level >15.0%, irrespective of concomitant treatment with HbF inducing treatments such as HU.
    9. History of untreated Moyamoya disease or presence of Moyamoya disease at Screening that in the opinion of the investigator puts the subjects at the risk of bleeding.
    10. History of a significant bleeding disorder.
    11. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject. This may include, but is not limited to: history of relevant drug allergies; history of cardiovascular or central nervous system disease; history or presence of clinically significant pathology; history of mental disease, or history of familial cancer syndrome.
    12. Any prior or current malignancy or myeloproliferative disorder or a significant immunodeficiency disorder.
    13. Advanced liver disease, defined as
    a. Alanine transaminase (ALT) >3 × the upper limit of normal (ULN) or direct bilirubin value >2 × ULN, or
    b. Baseline prothrombin time (PT) (international normalized ratio [INR]) >1.5 × ULN, or
    c. History of cirrhosis or any evidence of bridging fibrosis, or active hepatitis on liver biopsy
    14. Baseline estimated glomerular filtration rate <60 mL/min/1.73 m2.
    15. Lung diffusing capacity for carbon monoxide (DLco) <50% of predicted value (corrected for hemoglobin and/or alveolar volume).
    16. Left ventricular ejection fraction (LVEF) <45% by echocardiogram.
    17. Prior treatment with gene therapy/editing product.
    18. Intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Prior anaphylactic reaction with excipients of CTX001 product (dimethylsulfoxide [DMSO], dextran).
    19. Positive for the presence of human immunodeficiency virus-1 (HIV1) or human immunodeficiency virus-2 (HIV-2) (positive
    antigen/antibody AND nucleic acid tests [NAT]), hepatitis B virus (HBV)(positive Hepatitis B core antibody [HBcAb] AND NAT tests), syphilis (positive screening AND confirmatory tests), or hepatitis C virus (HCV; positive antibody [HCAb] AND NAT tests). Additional infectious disease markers should be obtained and tested as required by the local authority for the collection and processing of cellular therapy products. These additional tests (e.g., HTLV-1, HTLV-2, malaria, tuberculosis, toxoplasmosis,
    Trypanosoma cruzi, or West Nile virus) will be evaluated to determine overall impact to the subject and manufacturing of CTX001.
    20. Participation in another clinical study with an investigational drug/product within 30 days of screening or fewer than 5 half-lives of the investigational agent, whichever is longer from screening.
    21. Subjects who are not able to comply with the study procedures outlined in the protocol as judged by the investigator.
    22. Pregnant or breastfeeding females.
    1. Un donatore compatibile disponibile con una corrispondenza degli antigeni leucocitari umani (HLA) 10/10
    2. Precedente HSCT allogenico.
    3. Infezione batterica, virale, fungina o da parassita clinicamente significativa e attiva, determinata dallo sperimentatore.
    4. Conta dei globuli bianchi <3 × 109/L o conta piastrinica <50 × 109/L non correlata a ipersplenismo.
    5. Trattamento con trasfusioni regolari di globuli rossi che, secondo il parere dello sperimentatore, non può essere interrotto dopo l'attecchimento.
    6. Soggetti con storia di alloimmunizzazione a antigeni RBC e soggetti per cui l'investigatore prevede che ci sarà un numero insufficiente di globuli rossi unità disponibili per la durata dello studio.
    7. Più di 10 ricoveri non pianificati o visite al pronto soccorso relative a SCD nell'anno prima dello screening che, secondo il parere dello sperimentatore, sono coerenti con un significativo dolore cronico piuttosto che con crisi di dolore acuto.
    8. Livello di HbF> 15,0%, indipendentemente dal trattamento concomitante con l’emoglobina fetale (HbF) trattamenti che inducano HU.
    9. Storia della malattia di Moyamoya non trattata o presenza della malattia di Moyamoya allo Screening che secondo il parere dello sperimentatore mette il soggetto a rischio di sanguinamento
    10. Anamnesi di disturbo emorragico significativo.
    11. Anamnesi di qualsiasi malattia o condizione clinica che, a parere dello sperimentatore, possa confondere i risultati dello studio o porre un rischio aggiuntivo alla somministrazione del farmaco in studio al soggetto. Questo può comprendere, ma non è limitato a, anamnesi di allergie rilevanti a farmaci, anamnesi di malattia cardiovascolare compresa insufficienza cardiaca o malattia del sistema nervoso centrale, anamnesi o presenza di patologia clinicamente significativa, o anamnesi di malattia mentale.
    12. Qualsiasi precedente o attuale neoplasia maligna o disturbo mieloproliferativo o un disturbo significativo di immunodeficienza.
    13. Malattia epatica avanzata definita come:
    a. Aspartato transaminasi, alanina transaminasi >3× il limite superiore del valore normale (ULN), o valore di bilirubina diretta >2 x il limite superiore del valore normale (ULN), o:
    b. Tempo di protrombina basale (rapporto internazionale normalizzato; INR) >1.5 x ULN, oppure
    c. Anamnesi di cirrosi o qualsiasi evidenza di fibrosi a ponte, o epatite attiva su biopsia epatica.
    14. Velocità di filtrazione glomerulare stimata basale < 60 ml/min/1,73 m2.
    15. Capacità di diffusione polmonare del monossido di carbonio (DLco) <50% del previsto (corretto per emoglobina e/o volume alveolare).
    16. Frazione di eiezione ventricolare sinistra (LVEF) <45% mediante ecocardiogramma.
    17. Precedente trattamento con terapia genica.
    18. Intolleranza o sensibilità nota a plerixafor, prodotti G-CSF (ad es. filgrastim) o busulfan. Precedente anafilassi con eccipienti del prodotto CTX001 (dimetilsolfossido [DMSO], destrano).
    19. Sierologia positiva per HIV-1 o HIV-2, virus dell’epatite B (HBV) (anticorpo anti-core dell'epatite B [HHBcAb] e PCR positiva per HBV), sifilide (test di screening e conferma positivi), or hepatitis C virus (HCV;anticorpo positivo[HCAb] AND NAT tests). Ulteriori marcatori di malattie infettive devono essere ottenuti e testati come richiesto dalle autorità locali per la raccolta e l'elaborazione dei prodotti di terapia cellulare. Questi esami (ad es, HTLV-1, HTLV-2, malaria, tubercolosi, toxoplasmosi, Trypanosoma cruzi, o West Nile virus) saranno valutati per determinare l'impatto complessivo sul soggetto e sulla produzione di CTX001.
    20. Partecipazione ad un altro studio clinico con un farmaco sperimentale entro 30 giorni dallo screening o entro meno di 5 emivite del farmaco sperimentale, a seconda di quale sia maggiore dello screening.
    21. Una valutazione da parte dello sperimentatore che il soggetto non sarebbe conforme alle procedure dello studio delineate nel protocollo.
    22. Donne in stato di gravidanza o allattamento.
    E.5 End points
    E.5.1Primary end point(s)
    Primary Endpoints
    Safety Endpoints
    • Successful neutrophil engraftment within 42 days after CTX001 infusion
    • Time to neutrophil engraftment
    • Time to platelet engraftment
    • Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, and vital signs
    • Transplant-related mortality (TRM) within 100 days after CTX001 infusion
    •TRM within 1 year after CTX001 infusion
    • All-cause mortality
    Primary Efficacy Endpoint
    • Proportion of subjects with sustained fetal hemoglobin (HbF) =20% at the time of analysis for at least 3 months starting 6 months after
    Sicurezza:
    Attecchimento di neutrofili riuscito correttamente entro 42 giorni dall'infusione di CTX001
    • Tempo all'attecchimento di neutrofili
    • Tempo all'attecchimento di piastrine
    • Valutazioni di sicurezza e tollerabilità in base agli eventi avversi (EA), ai valori clinici di laboratorio e ai parametri vitali
    • Mortalità correlata a trapianto (Transplant-Related Mortality, TRM) entro 100 giorni dall'infusione di CTX001
    • TRM entro 1 anno dall'infusione di CTX001
    • Mortalità per qualunque causa
    Endpoint primario di efficacia:
    Percentuale di soggetti il cui valore di emoglobina fetale (HbF) sia =20% e costante per almeno 3 mesi a partire da 6 mesi dopo l'infusione di CTX001, in assenza di trattamento con idrossiurea (HydroxyUrea, HU).
    E.5.1.1Timepoint(s) of evaluation of this end point
    see above
    vedi sopra
    E.5.2Secondary end point(s)
    Key Secondary Efficacy Endpoint
    • Relative change from baseline in annualized rate of severe vaso-occlusive crises (VOC) , starting 6 months after CTX001 infusion
    Secondary Endpoints
    • Reduction in annualized rate of severe VOC from baseline by at least 50% at the time of analysis, starting 6 months after CTX001 infusion
    • Reduction in annualized rate of severe VOC from baseline by at least 65% at the time of analysis, starting 6 months after CTX001 infusion
    • Absence of severe VOC events for at least 12 months at the time of the analysis starting 6 months after CTX001 infusion

    • Relative Change from baseline in annualized duration of hospitalization for severe VOC, starting 6 months after CTX001 infusion
    • Proportion of subjects with sustained HbF =20% at the time of analysis for at least 3 months, starting 3 months after CTX001 infusion, in the absence of treatment with HU
    • Proportion of subjects with sustained HbF =20% at the time of analysis for at least 3 months, starting at the time of CTX001 infusion, in the absence of treatment with HU
    • Proportion of subjects with sustained HbF =20% at the time of analysis for 6 months, starting 6 months after CTX001 infusion, in the absence of treatment with HU
    • Change in number of units of red blood cells (RBC) transfused for SCD-related indications over time
    • HbF concentrations over time
    • Hemoglobin (Hb) concentrations over time
    • Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
    • Proportion of alleles with intended genetic modification present in bone marrow cells over time
    • Change in patient reported outcomes (PROs) over time using weekly Pain-scale (11 point numerical rating scale [NRS]), EuroQol Quality of Life Scale (EQ-5D-5L), functional assessment of cancer therapy-bone marrow transplant (FACT-BMT), and Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me)
    Efficacia secondaria:
    Variazione relativa, rispetto al basale, del tasso annualizzato di crisi vaso-occlusive (Vaso-Occlusive Crises, VOC) gravi, a partire da 6 mesi dopo l'infusione di CTX001.
    End point secondari:
    •Riduzione di almeno il 50% rispetto al basale del tasso annualizzato di VOC gravi al momento dell'analisi, a partire da 6 mesi dopo l'infusione di CTX001
    • Riduzione di almeno il 65% rispetto al basale del tasso annualizzato di VOC gravi al momento dell'analisi, a partire da 6 mesi dopo l'infusione di CTX001
    • Assenza di eventi VOC gravi per almeno 12 mesi al momento dell'analisi a partire da sei mesi dopo l'infuzione di CTX
    • Variazione relativa, rispetto al basale, della durata annualizzata del ricovero per VOC gravi, a partire da 6 mesi dopo l'infusione di CTX001
    • Percentuale di soggetti il cui valore HbF sia =20% al momento dell'analisi e costante per almeno 3 mesi, a partire da 3 mesi dopo l'infusione di CTX001, in assenza di trattamento con HU
    • Percentuale di soggetti il cui valore HbF sia =20% al momento dell'analisi e costante per almeno 3 mesi, a partire dal momento in cui avviene l'infusione di CTX001, in assenza di trattamento con HU
    •Percentuale di soggetti il cui valore HbF sia =20% al momento dell'analisi e costante per almeno 6 mesi, a partire da 6 mesi dopo l'infusione di CTX001, in assenza di trattamento con HU
    • Variazione nel tempo del numero di unità di eritrociti (Red Blood Cells, RBC) trasfusi per le indicazioni relative all'SCD
    • Concentrazioni di HbF nel tempo
    • Concentrazioni dell'emoglobina (Hb) nel tempo
    • Percentuale di alleli contenenti la modifica genetica prevista presenti, nel tempo, nei leucociti del sangue periferico
    • Percentuale di alleli contenenti la modifica genetica prevista presenti, nel tempo, nelle cellule del midollo osseo
    • Cambiamenti negli esiti riferiti dai pazienti (Partient-Reported Outcomes, PROs) nel tempo, utilizzando la Scala di valutazione del dolore (Scala di valutazione numerica a 11 punti, NRS) somministrata settimanalmente, il Questionario sulla Qualità della vita EuroQol (EQ-5D-5L), il Questionario di valutazione funzionale della terapia oncologica-trapianto di midollo osseo (FACT-BMT), nonché il Sistema per la misurazione della qualità della vita in adulti con anemia falciforme (ASCQ-Me)
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Any transfusion received will be documented from the time of consent until the end of the study
    • HbF concentrations: per month 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24
    • Hb concentrations over time
    • Proportion of alleles with desired genetic modification in peripheral blood leukocytes: per month 1, 2, 3, 4, 5, 6, 9, 12, 18, 24
    • Proportion of alleles with genetic modification desired in the bone marrow: at month 6, 12, 24
    • Changes in results reported by the patient (PROs):
    - EQ-5D-5L, FACT BMT, PROMIS Cognitive and ASCQ-Me: per month 3, 6, 12, 18, 24
    - Pain-Scale [11 point NRS], PROMIS-Fatigue: per month 3, 4, 5, 6, 9, 12, 15, 18, 21, 24
    • Qualsiasi trasfusione ricevuta sarà documentata dal momento del consenso fino alla fine dello studio
    • Concentrazioni HbF: al mese 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24
    • Concentrazioni Hb col tempo
    • Proporzione di alleli con modifica genetica voluta presente nei leucociti di sangue periferico: al mese 1, 2, 3, 4, 5, 6, 9, 12, 18, 24
    • Proporzione di alleli con modifica genetica voluta presente nel midollo osseo: al mese 6, 12, 24
    • Cambiamenti nei risultati riferiti dal paziente (PROs):
    - EQ-5D-5L, FACT BMT, PROMIS Cognitive and ASCQ-Me: al mese 3, 6, 12, 18, 24
    - Pain-Scale [11 point NRS], PROMIS-Fatigue: al mese 3, 4, 5, 6, 9, 12, 15, 18, 21, 24
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    phase 1 / phase 2
    fase 1/ fase 2
    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 No
    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.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA7
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    Belgium
    France
    Germany
    Italy
    United Kingdom
    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 the study is defined as the date on which the last subject will complete the 24-month follow-up period. The sponsor will notify all applicable regulatory agencies, in accordance with local requirements, when the study is finished.
    La fine dello studio è definita come la data in cui l'ultimo soggetto completerà il periodo di follow-up di 24 mesi. Lo sponsor notificherà a tutte le agenzie regolamentorie applicabili, in conformità con i requisiti locali, quando lo studio sarà finito.
    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 months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months2
    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: 45
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 45
    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 to participate in a long-term follow-up study or registry.
    A tutti i soggetti infusi con CTX001 sarà chiesto di partecipare ad uno studio o registro di follow-up a lungo termine.
    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 Decision2019-01-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-24
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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