E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
hidradenitis suppurativa |
hidradenitis supurativa |
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E.1.1.1 | Medical condition in easily understood language |
a long term skin disease characterized by the occurrence of inflamed and swollen lumps |
enfermedad cutánea crónica caracterizada por la aparición de bultos inflamados e hinchados |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020041 |
E.1.2 | Term | Hidradenitis suppurativa |
E.1.2 | System Organ Class | 100000004858 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of secukinumab (300 mg q4w or 300 mg q2w) in subjects with moderate to severe HS who were HiSCR responders at Week 52 of the core studies, with respect to loss of response by Week 104, compared to placebo. |
Demostrar la eficacia de secukinumab (300 mg c4s o 300 mg c2s) en pacientes con HS de moderada a grave que sean respondedores HiSCR en la semana 52 de los estudios principales, con respecto a la pérdida de respuesta a la semana 104 comparado con placebo. |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term safety and tolerability of secukinumab in subjects with moderate to severe HS evaluated by adverse events, abnormal laboratory values and vital signs.
To explore time to regain HiSCR response after treatment following loss of response. To explore the efficacy after uptitration from 300mg q4w to 300mg q2w. To evaluate the effect of secukinumab as interrupted or continuous treatment To evaluate the pharmacokinetics of AIN457 at the LOR visit, Exploratory biomarkers at LOR visits |
Evaluar la seguridad y tolerabilidad a largo plazo de secukinumab en pacientes con HS de moderada a grave evaluada mediante acontecimientos adversos, anomalías en los valores analíticos y constantes vitales.
Explorar el tiempo hasta recuperar respuesta HiSCR después del tratamiento tras la pérdida de respuesta. Explorar la eficacia después del ajuste ascendente de dosis de 300 mg c4s a 300 mg c2s. Evaluar el efecto de secukinumab como tratamiento interrumpido o continuado. - Evaluar la farmacocinética de AIN457 en la visita de PR y los biomarcadores exploratorios en las visitas de PR. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for inclusion in this study must meet all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Subjects who complete the whole study treatment period (52 weeks) in the core studies (CAIN457M2301 or CAIN457M2302) and have received secukinumab treatment during the Treatment Period 2 of the core studies. |
Los pacientes elegibles para su inclusión en este estudio deben cumplir todos los siguientes criterios: 1. El consentimiento informado por escrito se debe obtener antes de realizar cualquier evaluación. 2. Pacientes que hayan completado el periodo de tratamiento del estudio (52 semanas) de los «estudios principales» (CAIN457M2301 o CAIN457M2302) y que hayan recibido tratamiento con secukinumab durante el periodo de tratamiento 2 de los «estudios principales». |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for inclusion in this study. 1. A protocol deviation in the core study which, according to the investigator will prevent the meaningful analysis of the extension study for the individual subject. 2. Ongoing or planned use of prohibited HS or non-HS treatments. Time of use of prohibited treatments in the core study must continue to be adhered to. 3. Subjects not expected to benefit from participation in the extension study, as assessed by the subject and investigator. 4. Subjects whose participation in the extension study could expose them to an undue safety risk. 5. Current severe progressive or uncontrolled disease which in the judgment of the investigator renders the subject unsuitable for the study. 6. Plans for administration of live vaccines during the study. 7. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g. in European Union (EU) 20 weeks). Contraception methods include: Total abstinence, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have had surgical bilateral oophorectomy [with or without hysterectomy], total hysterectomy or tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository. Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). |
Los pacientes que cumplan alguno de los siguientes criterios no son elegibles para su inclusión en este estudio: 1. Una desviación del protocolo en el estudio principal que, de acuerdo con el investigador, impida el análisis significativo del estudio de extensión para un paciente individual. 2. Uso actual o previsto de tratamientos prohibidos para la HS o que no sean para la HS. El tiempo de uso de los tratamientos prohibidos en el estudio principal debe continuar cumpliéndose (véase la Tabla 6-2). 3. Pacientes que no se prevea que vayan a beneficiarse de la participación en el estudio de extensión, según la evaluación del paciente y del investigador. 4. Pacientes cuya participación en el estudio de extensión pudiera exponerles a un riesgo de seguridad indebido. 5. Enfermedad actual progresiva grave o no controlada que según el investigador conlleve que el paciente no sea apto para el estudio. 6. Previsión de administración de vacunas vivas durante el estudio. 7. Mujeres en edad fértil, definidas como toda mujer fisiológicamente capaz de quedarse embarazada, salvo que esté utilizando métodos anticonceptivos durante todo el estudio o durante más tiempo si así lo indica el prospecto local aprobado (p. ej., 20 semanas en la Unión Europea [UE]). Los métodos anticonceptivos incluyen: Abstinencia total, cuando esté en consonancia con el estilo de vida habitual y preferido del paciente. Abstinencia periódica (p. ej., calendario, ovulación, métodos sintotérmicos o posovulación) y el coitus interruptus no son métodos anticonceptivos aceptables. Esterilización femenina (cuando se le haya realizado una ooforectomía bilateral [con o sin histerectomía], histerectomía total o ligadura de trompas al menos seis semanas antes de recibir el tratamiento del estudio). Si solo se ha realizado ooforectomía, únicamente cuando se haya confirmado el estado reproductor de la mujer mediante la evaluación de seguimiento del nivel hormonal. Métodos anticonceptivos de barrera: preservativo o capuchón oclusivo (diafragma o capuchón en bóveda/cervical). En Reino Unido: con espuma/gel/película/crema espermicida/supositorio vaginal. Uso de métodos anticonceptivos hormonales orales (estrógeno y progesterona), inyectados o implantados u otros métodos anticonceptivos hormonales que tengan una eficacia comparable (tasa de fallo <1 %), por ejemplo, anillo vaginal hormonal o anticonceptivo hormonal transdérmico, o colocación de un dispositivo intrauterino (DIU) o sistema intrauterino (SIU). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to loss of response up to Week 104 (Randomized Withdrawal period) in subjects who were HiSCR responders at Week 52 in the core studies. HiSCR response is defined as at least 50% decrease in Abscess and inflammatory Nodule (AN) number with no increase in the number of abscesses and in the number of draining fistulae. Loss of response is defined as: 1. at least a 50% or greater increase in AN (abscess and/or nodules) at a regular or unscheduled visit compared to the average AN count from 3 previous visits or the Week 52 whichever is lower and the increase is at least of 3 AN . 2. If at a regular or unscheduled visit, the subject experiences at least a 30% increase in AN compared to the average AN count from the 3 previous visits or the Week 52 visit whichever is lower with an increase of at least 2 AN, the subject should be reassessed within 2-4 weeks. A further increase in the AN count of at least 2 AN would be considered a LOR also. Note: If the 3 previous visits include visits from core studies, the AN count from the core study will be included in the average. |
Tiempo hasta la pérdida de respuesta hasta la semana 104 (periodo de retirada aleatorizada) en pacientes que hayan sido respondedores HiSCR en la semana 52 de los estudios principales. La respuesta HiSCR se define como una disminución de al menos un 50 % en el número de abscesos y nódulos inflamatorios (AN) sin incremento en el número de abscesos ni en el número de fístulas drenantes. La pérdida de respuesta se define como:
• Un incremento de al menos un 50 % en AN (abscesos o nódulos) en una visita periódica o no programada comparado con el recuento medio de AN de las tres visitas anteriores o de la semana 52, aquel que sea más bajo, y que el incremento sea al menos de 3 AN respecto al recuento medio de AN de las tres visitas anteriores.
• Si en una visita periódica o no programada el paciente presenta un incremento de al menos un 30 % en AN comparado con el recuento medio de AN de las tres visitas anteriores o de la semana 52, aquel que sea más bajo, con un incremento de al menos 2 AN respecto al recuento medio de las tres visitas anteriores, se volverá a evaluar al paciente en las próximas 2-4 semanas. Otro incremento en el recuento de AN de al menos 2 AN también se consideraría una PR.
Nota: si las tres visitas anteriores incluyen visitas de los estudios principales, el recuento de AN de los estudios principales se incluirá en la media. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blinded part - HiSCR at 52 weeks of core studies Primary end point will be assessed at End of Treatment (EOT) -1): Loss of response (LOR) by 104 weeks |
Parte ciega - HiSCR a las 52 semanas de los estudios principales La variable principal será evaluada al final del tratamiento (EOT) -1: Pérdida de respuesta (PR) a las 104 semanas. |
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E.5.2 | Secondary end point(s) |
Adverse events, laboratory values, vital signs. Time to regain HiSCR response following loss of response HiSCR, flare, NRS30 after up-titration |
Acontecimientos adversos, valores analíticos y constantes vitales. Tiempo para recuperar la respuesta HiSCR después de la pérdida de respuesta HiSCR, brotes, NRS30 después del aumento de dosis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After LOR has been attained, the subject will receive open label treatment with secukinumab and continue in the study for the maximum duration of 260 weeks of treatment plus 8 weeks of the post-treatment follow-up period in total or, until secukinumab is commercially available for a given trial participant. |
Después de que la PR haya sido alcanzada, el paciente recibirá el tratamiento abierto con secukinumab y continuará en el estudio durante un máximo de 260 semanas de tratamiento más un periodo de 8 semanas de seguimiento postratamiento en total o, hasta que secukinumab esté comercialmente disponible para un participante de ensayo dado. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 129 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Colombia |
Croatia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Guatemala |
Hungary |
India |
Israel |
Italy |
Korea, Democratic People's Republic of |
Lebanon |
Lithuania |
Malaysia |
Mexico |
Netherlands |
Philippines |
Poland |
Portugal |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
Vietnam |
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E.8.7 | Trial 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
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LVLS |
Última visita del Último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |