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    Summary
    EudraCT Number:2014-004787-37
    Sponsor's Protocol Code Number:VX14-661-107
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-08-25
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2014-004787-37
    A.3Full title of the trial
    A Phase 3, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
    Estudio fase 3, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos para evaluar la eficacia y seguridad de VX-661 en combinación con Ivacaftor en sujetos a partir de 12 años con fibrosis quística, heterocigóticos para la mutación F508del-CFTR y una segunda mutación del CFTR que no sea probable que respondan al tratamiento con VX-661 y/o Ivacaftor (F508del/no respondedores)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study in people with Cystic Fibrosis (a rare hereditary lung disease) to assess the efficacy and safety of a combination of two experimental drugs.
    Estudio en personas con fibrosis quística (una enfermedad pulmonar hereditaria rara) para evaluar la eficacia y seguridad de una combinación de farmacos experimentales.
    A.4.1Sponsor's protocol code numberVX14-661-107
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/098/2015
    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, Massachusetts
    B.5.3.3Post code02210
    B.5.3.4CountryUnited States
    B.5.4Telephone number1877634-8789
    B.5.5Fax number1510595-8183
    B.5.6E-mailmedical_info@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 numberEU/3/14/1281
    D.3 Description of the IMP
    D.3.1Product nameVX-661/ivacaftor 100mg/150mg
    D.3.2Product code VX-661/VX-770
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral 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 1152311-62-0
    D.3.9.2Current sponsor codeVX-661
    D.3.9.3Other descriptive nameVRT-893661 VRT-0893661
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIVACAFTOR
    D.3.9.1CAS number 873054-44-5
    D.3.9.2Current sponsor codeVX-770
    D.3.9.4EV Substance CodeSUB33103
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Kalydeco
    D.2.1.1.2Name of the Marketing Authorisation holderVertex Pharmaceuticals Incorporated
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/008/556
    D.3 Description of the IMP
    D.3.1Product nameivacaftor
    D.3.2Product code VX-770, VRT-813077
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIVACAFTOR
    D.3.9.1CAS number 873054-44-5
    D.3.9.2Current sponsor codeVX-770
    D.3.9.4EV Substance CodeSUB33103
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cystic Fibrosis
    Fibrosis Quística
    E.1.1.1Medical condition in easily understood language
    Cystic Fibrosis
    Fibrosis Quística
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10011762
    E.1.2Term Cystic fibrosis
    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 evaluate the efficacy of VX-661 in combination with ivacaftor through Week 12 in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy (F508del/not responsive [NR])
    Evaluar la eficacia de VX-661 en combinación con ivacaftor hasta la semana 12 en sujetos con fibrosis quística (FQ) heterocigóticos para la mutación F508del en el gen regulador de la conductancia transmembrana de la FQ (CF transmembrane conductance regulator, CFTR) y en un segundo alelo con una mutación en el CFTR que no es probable que responda al tratamiento con VX-661 y/o ivacaftor (F508del/no respondedores [NR]).
    E.2.2Secondary objectives of the trial
    To evaluate the safety of VX-661 in combination with ivacaftor and to investigate the pharmacokinetics (PK) of VX-661 and its metabolite M1-661, and ivacaftor and its metabolite M1-ivacaftor
    Evaluar la seguridad de VX-661 en combinación con ivacaftor y Investigar la farmacocinética (FC) de VX-661 y su metabolito M1-661, y de ivacaftor y su metabolito M1-ivacaftor.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Heterozygous for the F508del CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy, genotype to be confirmed via assessment at the Screening Visit.

    Confirmed diagnosis of CF defined as a sweat chloride value ?60 mmol/L by quantitative pilocarpine iontophoresis (as documented in the subject?s medical record OR from sweat chloride test result obtained at the Screening, if subject does not have a sweat chloride test result in the medical record).

    FEV1 ?40% and ?90% of predicted normal for age, sex, and height at Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability.

    Stable CF disease as judged by the investigator.

    Willing to remain on a stable CF medication regimen through Week 12 or, if applicable, the Safety Follow-up Visit.
    Heterocigóticos para la mutación F508del-CFTR y con una segunda mutación de CFTR que no es probable que responda al tratamiento con VX-661 y/o ivacaftor el genotipo se debe confirmar mediante evaluación en la visita de selección.

    Diagnóstico confirmado de FQ, definida como un valor de cloruro en sudor ? 60 mmol/l mediante iontoforesis cuantitativa con pilocarpina (como se documenta en la historia clínica del sujeto O a partir del resultado de la prueba de cloruro en el sudor obtenido durante la investigación si el sujeto no tiene un resultado de la prueba de cloruro en el sudor en la historia clínica).

    VEF1 ? 40 % y ? 90 % de valor normal previsto para la edad, el sexo y la estatura durante la selección. Las mediciones de la espirometría deben cumplir los criterios de la Sociedad Torácica Americana/Sociedad Respiratoria Europea de aceptabilidad y repetibilidad.

    Enfermedad de la FQ estable, a juzgar por el investigador.

    Disponibilidad para permanecer en una pauta estable de medicación para la FQ hasta la semana 12 o, si corresponde, hasta la visita de seguimiento de la seguridad.
    E.4Principal exclusion criteria
    History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.

    An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).

    Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1.
    Antecedentes de alguna comorbilidad que, en opinión del investigador, podría confundir los resultados del estudio o suponer un riesgo adicional en la administración del fármaco del estudio al sujeto.

    Infección aguda del tracto respiratorio superior o inferior, exacerbación pulmonar o cambios en el tratamiento (incluidos los antibióticos) para la enfermedad pulmonar en los 28 días antes del día 1 (primera dosis del fármaco del estudio).

    Mujeres embarazadas y lactantes: las mujeres en edad fértil deben presentar un test de embarazo negativo en el momento de la selección y el día 1.
    E.5 End points
    E.5.1Primary end point(s)
    Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline through Week 12.
    Cambio absoluto desde el inicio en el porcentaje del VEF1 previsto hasta la semana 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 12
    Semana 12
    E.5.2Secondary end point(s)
    Relative change in percent predicted FEV1 from baseline through Week 12

    Absolute change in sweat chloride from baseline through Week 12

    Absolute change in body mass index (BMI) from baseline at Week 12

    Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline through Week 12

    Number of pulmonary exacerbations through Week 12

    Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values (i.e., hematology, coagulation studies, serum chemistry, vitamin levels, lipid panel, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry

    Time-to-first pulmonary exacerbation through Week 12

    Absolute change in BMI z-score from baseline at Week 12 (in subjects <20 years old at time of screening)

    Absolute change in body weight from baseline at Week 12

    PK parameters of VX-661, M1-661, ivacaftor, and M1 ivacaftor
    Tiempo hasta la primera exacerbación pulmonar hasta la semana 12.

    Cambio absoluto en el cloruro del sudor desde el inicio hasta la semana 12

    Cambio absoluto en la puntuación z del IMC desde el inicio en la semana 12

    Cambio absoluto en la puntuación de gravedad del diario de síntomas respiratorios de la fibrosis quística (Cystic Fibrosis Respiratory Symptom Diary, CFRSD) desde el inicio hasta la semana 12.

    Número de exacerbaciones pulmonares hasta la semana 12.

    Evaluaciones de seguridad y tolerabilidad basadas en acontecimientos adversos (AA), valores analíticos clínicos (es decir, hematología, estudios de coagulación, bioquímica sérica, niveles de vitaminas, panel de lípidos y análisis de orina), electrocardiogramas (ECG) digitales estándar, constantes vitales, oximetría de pulso y espirometría.

    Tiempo hasta la primera exacerbación pulmonar hasta la semana 12.

    Cambio absoluto en la puntuación z del IMC desde el inicio en la semana 12 (en sujetos < 20 años de edad en el momento de la selección).

    Cambio absoluto en el peso corporal desde el inicio en la semana 12.

    Parámetros FC de VX-661, M1-661, ivacaftor y M1-ivacaftor.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12
    Semana 12
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA19
    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
    Austria
    Canada
    France
    Germany
    Israel
    Spain
    United States
    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 years2
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    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: 150
    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: 150
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 150
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children, age 12-17 years old, are included in the study
    Se incluiran niños de entre 12-17 años en el estudio
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 95
    F.4.2.2In the whole clinical trial 300
    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 conclusion of the patient's participation in the clinical study, the patient will return to their standard treatment for Cystic Fibrosis and subjects who complete the Week 12 Visit, regardless of whether they have prematurely discontinued study drug treatment, may be offered the opportunity to enroll in an extension study, if they meet the eligibility criteria for the extension study.
    Tras la finalización de la participación del paciente en el estudio clínico, el paciente regresará a su tratamiento estándar para la fibrosis quística y a los sujetos que completen la visita de la Semana 12, independientemente de si han interrumpido prematuramente el tratamiento del fármaco del estudio, se podrá ofrecer la oportunidad de inscribirse en un estudio de extensión, si cumplen con los criterios de elegibilidad para el estudio de extensión.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-10-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-05-27
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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