E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ankylosing spondylitis |
Espondilitis anquilosante |
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E.1.1.1 | Medical condition in easily understood language |
Ankylosing spondylitis or AS, is a form of arthritis that primarily affects the spine and sacroiliac joints, although other joints can become involved. |
La espondilitis anquilosante or EA, es un tipo de artritis que afecta principalmente a la columna vertebral y a las articulaciones sacroiliacas, aunque otras articulaciones pueden estar involucradas. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002556 |
E.1.2 | Term | Ankylosing spondylitis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 |
Demonstrate the efficacy of bimekizumab administered subcutaneously (sc) compared to placebo in the treatment of subjects with active ankylosing spondylitis (AS) |
Demostrar la eficacia de bimekizumab administrado por vía subcutánea (sc), en comparación con placebo, en el tratamiento de sujetos con espondilitis anquilosante (AS) activa. |
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E.2.2 | Secondary objectives of the trial |
- Assess the efficacy of bimekizumab compared to placebo - Assess the safety and tolerability of bimekizumab - Assess the impact of bimekizumab on patient-reported quality of life - Assess the impact of bimekizumab on spinal mobility - Assess the impact of bimekizumab on enthesitis and on peripheral arthritis |
- Evaluar la eficacia de bimekizumab comparado con placebo - Evaluar la seguridad y la tolerabilidad de bimekizumab - Evaluar el efecto de bimekizumab sobre la calidad de vida comunicada por el paciente - Evaluar el efecto de bimekizumab sobre la movilidad de la columna vertebral - Evaluar el efecto de bimekizumab sobre la entesitis y sobre la artritis periférica |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There will be two optional substudies: a pharmacogenomic substudy and a magnetic resonance imaging (MRI) substudy. For subjects consenting to the genomics, genetics, and proteomics substudy, blood samples and stool samples will be drawn for exploratory genetic/epigenetic, genomic, proteomic, and metabolomics analysis and for candidate exploratory biomarker analyses. For subjects participating in the MRI substudy further sacroiliac joint and spine MRIs will be performed. |
Habrá dos subestudios opcionales: un subestudio farmacogenómico y un subestudio de resonancia magnética (MRI). Para los sujetos que consientan el subestudio de genómica, genética y proteómica, se extraerán muestras de sangre y de heces para análisis genéticos / epigenéticos, genómicos, proteómicos y metabólicos exploratorios y para análisis de biomarcadores exploratorios. Para los sujetos que participan en el subestudio de RM, se realizarán más resonancias magnéticas de la articulación sacroilíaca y la columna vertebral |
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E.3 | Principal inclusion criteria |
-Male or female patients at least 18 years of age -Subject has ankylosing spondylitis as per the Modified New York (mNY) criteria with documented radiologic evidence, and at least 3 months of symptoms with age at symptom onset less than 45 years -Subjects has moderate-to-severe active disease defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >=4 AND spinal pain >=4 on a 0 to 10 Numeric Rating Scale -Patients must have inadequate response to NSAIDs, intolerance to administration of at least 1 NSAID, or contraindication(s) to NSAID therapy -Patients who have taken a tumor necrosis factor alpha (TNFα) inhibitor must have experienced an inadequate response or intolerance to treatment given at an approved dose for at least 12 weeks -Patients currently taking NSAIDs, cyclooxygenase 2 (COX-2) inhibitors, analgesics, corticosteroids, methotrexate (MTX), leflunomide (LEF), sulfasalazine (SSZ), hydroxychloroquine (HCQ) AND/OR apremilast can be allowed if they fulfill specific requirements prior to study entry |
-El sujeto es varón o mujer de al menos 18 años. -El sujeto padece espondilitis anquilosante según los criterios de Nueva York modificados (mNY), con evidencia radiológica documentada y con al menos 3 meses de síntomas y edad al comienzo de estos <45 años -Sujeto con enfermedad activa de grado moderado o severo definido por el Índice de actividad de la espondilitis anquilosante de Bath (BASDAI) >=4 Y raquialgia >= en una escala de valoración numérica de 0 a 10. -Pacientes con respuesta inadecuada al tratamiento con antiinflamatorios no esteroideos, intolerancia a la administración de al menos un antiinflamatorio no esteroideo, o contraindicación al tratamiento con antiinflamatorios no esteroideos -Los sujetos que hayan recibido un inhibidor del TNFα deberán haber presentado una respuesta insuficiente al tratamiento previo, administrado a la dosis aprobada durante por lo menos 12 semanas, o intolerancia al tratamiento. -Los sujetos que tomen habitualmente antiinflamatorios no esteroideos/inhibidores de la ciclooxigenasa 2 (COX-2), analgésicos corticoesteroides, metotrexano (MTX), leflunomida (LEF), sulfasalazina (SSZ), hidroxicloroquina (HCQ) y/o apremilast serán permitidos siempre que cumplan los requerimientos específicos antes de entrar en el estudio |
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E.4 | Principal exclusion criteria |
-Total ankylosis of the spine -Treatment with more than 1 TNFα inhibitor and/or more than 2 additional non-TNFα biological response modifiers, or any interleukin (IL)-17 biological response modifier at any time are excluded -Active infection or history of recent serious infections -Viral hepatitis B or C or human immunodeficiency virus (HIV) infection -Any live (includes attenuated) vaccination within the 8 weeks prior to entering the study or TB (Bacillus Calmette-Guerin) vaccination within 1 year prior entering the study -Known tuberculosis (TB) infection, at high risk of acquiring TB infection, or current or history of nontuberculous mycobacterium (NTMB) infection -Subject has any active malignancy or history of malignancy within 5 years prior to the Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma or in situ cervical cancer -Diagnosis of inflammatory conditions other than AxSpA, eg, rheumatoid arthritis. Patients with a diagnosis of Crohn’s disease, ulcerative colitis, or other inflammatory bowel disease (IBD) are allowed as long as they have no active symptomatic disease when entering the study -Presence of active suicidal ideation, or moderately severe major depression or severe major depression -Female patients who are breastfeeding, pregnant, or planning to become pregnant during the study -Subject has a history of chronic alcohol or drug abuse within 6 months prior to Screening |
-Sujetos con anquilosis vertebral total. -Sujetos que hayan recibido en cualquier momento más de un inhibidor del TNFα y/o más de 2 modificadores de la respuesta biológica adicionales distintos de los inhibidores del TNFα o cualquier modificador de la respuesta biológica de tipo IL-17. -Sujeto con infección activa o antecedentes infecciosos -Sujeto con infección por los virus de las hepatitis B o C o de la inmunodeficiencia humana (HIV). -Sujeto que ha recibido una vacuna de gérmenes vivos (incluso atenuados) en el plazo de las 8 semanas previas a la Visita Basal o una vacuna antituberculosa (bacilo de Calmette y Guérin, BCG) en el plazo del año previo a la Visita Basal. -Sujeto con tuberculosis (TB), con elevado riesgo de contraer esta infección o con infección actual o pasada por una micobacteria no tuberculosa. -Sujeto con neoplasia maligna activa o antecedentes de neoplasia en el plazo de los 5 años previos a la Visita de Selección, EXCEPTO el carcinoma cutáneo espinocelular o basocelular o el carcinoma in situ de cuello uterino que se consideren curados. -Sujeto con diagnóstico de trastornos inflamatorios distintos de la axSpA, como, entre otros, artritis reumatoide. Se permite participar a los sujetos con diagnóstico de enfermedad de Crohn, colitis ulcerosa u otra enfermedad inflamatoria intestinal, siempre que no presenten enfermedad sintomática activa en la Selección o en el momento Basal. -Presencia de ideación suicida activa o con depresión mayor moderadamente severa o severa -Mujer en periodo de lactancia, embarazada o que tenga previsto quedarse embarazada durante el estudio -Sujeto con antecedentes de abuso crónico de alcohol o drogas en el plazo de los 6 meses previos a la Selección |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 16 |
Respuesta del 40% según la Sociedad Internacional de Espondiloartritis (Spondylo Arthritis International Society 40%, ASAS40) en la semana 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, Week 16 |
Basal, semana 16 |
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E.5.2 | Secondary end point(s) |
1. Assessment of SpondyloArthritis International Society 40% response criteria (ASAS40) response in TNFα inhibitor-naïve subjects at Week 16 2. Assessment of SpondyloArthritis International Society 20% response criteria (ASAS20) response at Week 16 3. Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 16 4. Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR) at Week 16 5. Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) at Week 16 6. Assessment of SpondyloArthritis International Society (ASAS) 5/6 response at Week 16 7. Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16 8. Change from Baseline in nocturnal spinal pain Numeric Rating Scale (NRS) at Week 16 9. Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16 10. Change from Baseline in the Short Form 36-Item Health Survey (SF-36) physical component summary (PCS) at Week 16 11. Change from Baseline in Bath Ankylosing Spondylitis Disease Metrology Index (BASMI) at Week 16 12. Change from Baseline in the Maastricht Ankylosing Spondylitis Enthesitis (MASES) Index in the subgroup of subjects with enthesitis at Baseline at Week 16 13. Enthesitis-free state based on the Maastricht Ankylosing Spondylitis Enthesitis Index (MASES) Index in the subgroup of subjects with enthesitis at Baseline at Week 16 14. Incidence of treatment-emergent adverse events (TEAEs) during the study 15. Incidence of serious adverse events (SAEs) during the study 16. Adverse events (AEs) leading to withdrawal from investigational medicinal product (IMP) during the study |
1. Respuesta ASAS40 en la Semana 16 en sujetos no tratados nunca con inhibidores del TNFα 2. Respuesta ASAS20 en la Semana 16 3. Variación respecto al valor Basal del BASDAI en la Semana 16 4. Remisión parcial según ASAS (ASAS-PR) en la Semana 16 5. Mejoría importante de la puntuación de la actividad de la espondilitis anquilosante (ASDAS-MI) en la Semana 16 6. Respuesta ASAS5/6 en la Semana 16 7. Variación respecto al valor Basal del índice funcional de espondilitis anquilosante de Bath (BASFI) en la Semana 16 8. Variación respecto al valor Basal de la raquialgia nocturna (NRS) en la Semana 16 9. Variación respecto al valor Basal del instrumento de la calidad de vida con espondilitis anquilosante (ASQoL) en la Semana 16 10. Variación respecto al valor Basal del resumen del componente físico (PCS) de la encuesta de salud abreviada de 36 ítems (SF-36) en la Semana 16 11. Variación respecto al valor Basal del índice metrológico de espondilitis anquilosante de Bath (BASMI) en la Semana 16 12. Variación respecto al valor Basal del índice de entesitis en la espondilitis anquilosante de Maastricht (MASES) en el subgrupo de sujetos con entesitis en el momento Basal, en la Semana 16 13. Ausencia de entesitis según el índice MASES en el subgrupo de sujetos con entesitis el momento Basal, en la Semana 16 14. Incidencia de acontecimientos adversos surgidos en el tratamiento (TEAE) durante el estudio 15. Incidencia de acontecimientos adversos graves (SAEs) durante el estudio 16. Acontecimientos adversos (AE) que lleven a la retirada del medicamento en investigación |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-13. Baseline, Week 16 14.-16. From Baseline (Day 1) until Safety Follow-Up (up to Week 72) |
1. -13. Basal, semana 16 14.-16. Desde el valor basal (día 1) hasta el seguimiento de seguridad (hasta la semana 72) |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity, Tolerability |
Inmunogenia, Tolerabilidad |
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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 | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 |
Belgium |
Bulgaria |
China |
Czech Republic |
France |
Germany |
Hungary |
Japan |
Netherlands |
Poland |
Spain |
Turkey |
United Kingdom |
United States |
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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
|
LVLS |
Ultima Visita del Ultimo Sujeto (LVLP) |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 3 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 26 |