Resumen

Ensayo clínico aleatorizado, doble ciego, para evaluar la seguridad y eficacia de dos dosis de cladribina oral versus placebo en participantes que presentaron un primer evento clínico desmielinizante (síndrome clínicamente aislado). Los participantes en el grupo de cladribina o placebo también podrán ingresar a períodos de tratamiento con interferón beta en abierto o cladribina en abierto según el estado de la enfermedad. El objetivo primario de este estudio es evaluar el efecto de dos regímenes posológicos de cladribina oral versus placebo sobre el tiempo hasta la conversión a esclerosis múltiple (EM) (desde la aleatorización) según los criterios de Poser, en participantes con primer evento clínico desmielinizante con alto riesgo de conversión a EM.

Descripción detallada

Se trata de un ensayo aleatorizado, doble ciego, de tres brazos, controlado con placebo y multicéntrico para evaluar la seguridad y eficacia de cladribina oral versus placebo en el tratamiento de participantes que han sufrido un primer evento clínico desmielinizante dentro de los 75 días previos al tamizaje. Los participantes deben presentar un mínimo de 2 lesiones clínicamente silentes en la resonancia magnética (RM) del tamizaje. El estudio incluirá un período de evaluación previa al estudio (período de tamizaje: entre 10 y 28 días antes del inicio del tratamiento con la medicación del estudio enmascarada [cladribina oral o placebo]). Según la evolución clínica de su EM, los participantes pasarán del PIT al Período de Tratamiento de Mantenimiento (con tratamiento en abierto con interferón beta) o al período de SFALT (con cladribina en abierto a dosis bajas o sin tratamiento adicional [si no se ha observado progresión a EM tras el período de tratamiento inicial]). El criterio de valoración primario único para el estudio global, que se determinará durante el PIT, es el tiempo hasta la conversión a EM (desde la aleatorización), según los criterios de Poser. Para cada participante, la elegibilidad para la inclusión en el estudio y el ingreso a cada período del estudio, así como el diagnóstico de conversión a EM McDonald o EMCD, deben ser confirmados y aprobados por un Comité de Adjudicación del Estudio designado por el patrocinador.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 55 YearsSexo: ALL

Criterios de inclusión

Male or female between 18 and 55 years old, inclusive
Weighed between 40 to 120 kilogram (kg), inclusive
Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic
Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI
Participant has EDSS 0 - 5.0 at Screening
Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray
Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments
If female, she must:
be neither pregnant nor breast-feeding, nor attempting to conceive and
use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or
be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial)
Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication
Be willing and able to comply with study procedures for the duration of the study
Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care
Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study

Criterios de exclusión

Participant has a diagnosis of MS (per McDonald criteria, 2005)
Participant has any other disease that could better explain the participant's signs and symptoms
Participant has complete transverse myelitis or bilateral optic neuritis
Participant using or has used any other approved MS disease modifying drug (DMD)
Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly.
Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal
Participant suffered from current autoimmune disease other than MS
Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol
Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
Participant has a history of seizures not adequately controlled by medications
Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate \[GFR\] less than 30 milliliter per minute per 1.73 square meter \[mL/min/1.73 m\^2\])
Participant has a history of chronic or clinically significant hematological abnormalities
Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive \[HIV+\], human T-lymphotrophic virus \[HTLV-1\], Lyme disease, latent tuberculosis infection \[LTBI\] or TB, insulin-dependent diabetes).
Participant has previously been screened in this study (signed an informed consent) and then withdrawn
Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 \[CD4\]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy
Participant has received experimental MS treatment
Participant has a history of alcohol or drug abuse
Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
Participant has inability to administer subcutaneous injections either by self or by caregiver
Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years)
Participant has a positive stool hemoccult test at Screening

Intervenciones

drug

Cladribine

Cladribine tablets were administered until CDMS conversion, whichever occur first.

drug

Placebo

Placebo matched to cladribine tablets were administered.

drug

Rebif® new formulation (RNF)

Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.

Ensayo Clínico de Fase III, Aleatorizado, Doble Ciego, Controlado con Placebo y Multicéntrico de Cladribina Oral en Sujetos con un Primer Evento Clínico con Alto Riesgo de Conversión a EM

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Cladribine

Placebo

Rebif® new formulation (RNF)

Ubicaciones

Instituto Medico Rodriguez Alfici

Fundacion Rosarina de Neurorehabilitacion

Patrocinadores