Resumen

Este es un estudio de extensión abierto (OLES) para pacientes que participaron en el ensayo clínico de fase III, doble ciego, controlado con placebo, de 18 meses de duración (protocolo ALX1-11-93001, estudio TOP) que estudió el efecto de ALX1-11, hormona paratiroidea humana recombinante, rhPTH(1-84), sobre la incidencia de fracturas vertebrales. El objetivo primario de este estudio es evaluar la seguridad de la administración continuada de ALX1-11, hasta un máximo de 24 meses, en mujeres con osteoporosis posmenopáusica que participaron en el protocolo ALX1-11-93001.

Descripción detallada

Los efectos de ALX1-11 sobre la densidad mineral ósea (DMO) han sido documentados en un ensayo clínico de fase II de búsqueda de dosis en mujeres posmenopáusicas con osteoporosis, suplementadas con calcio y vitamina D3 pero sin ningún otro tratamiento para la osteoporosis. Los efectos anabólicos de ALX1-11 en las vértebras lumbares fueron estadísticamente significativos después del período de tratamiento de 12 meses y más pronunciados que cualquier terapia aprobada. Adicionalmente, los estudios en animales han demostrado que el hueso nuevo formado por el tratamiento con ALX1-11 es de buena calidad tanto histológica como biomecánicamente. El objetivo primario de este OLES es evaluar la seguridad de la administración continuada de ALX1-11, hasta un máximo de 24 meses, en mujeres con osteoporosis posmenopáusica que participaron en el protocolo ALX1-11-93001. Un objetivo secundario es evaluar el cambio en la DMO vertebral y comparar los cambios observados en pacientes que recibieron ALX1-11 o placebo en el protocolo ALX1-11-93001. Las pacientes recibirán 100 µg/día de ALX1-11 diariamente mediante inyección subcutánea en este estudio. Las pacientes deben continuar con la frecuencia de administración del fármaco del estudio que seguían al final del protocolo ALX1-11-93001. Para mejorar su seguridad, todas las pacientes continuarán tomando sus suplementos diarios de 700 mg de calcio y 400 UI de vitamina D3 antes y durante este OLES. Las pacientes cuyo suplemento de calcio fue discontinuado durante el protocolo ALX1-11-93001 deben mantener dicha discontinuación durante este OLES. Sin embargo, al completar la administración de ALX1-11 en el OLES, el suplemento oral de calcio a una dosis de 700 mg cada mañana debe reiniciarse y mantenerse durante el resto del OLES. No se permitirá calcio y/o vitamina D3 suplementarios adicionales. Se podrá tomar un suplemento multivitamínico diario durante el estudio. Sin embargo, el multivitamínico no debe contener más de 200 mg/día de calcio y 400 UI/día de vitamina D3. Las pacientes serán monitoreadas para el desarrollo de hipercalcemia y/o hipercalciuria y manejadas según se describe en los apéndices 4 y 5. Habrá una regla de suspensión en este OLES. Cualquier paciente que alcance un puntaje T de DMO de -0,5 o superior, en el sitio o sitios (vertebral, cadera total o cuello femoral) que fueron utilizados para la calificación de la paciente para el protocolo ALX1-11-93001, suspenderá el tratamiento con ALX1-11. La paciente debe continuar con calcio y vitamina D3 y ser seguida durante el resto de este OLES de 18 meses. Al momento de la discontinuación, la paciente debe completar las evaluaciones del mes 18 (apéndice 1A o 1B). El Comité Asesor Clínico (CAB) utilizado en el protocolo ALX1-11-93001 participará en la revisión de cualquier problema de las pacientes que surja en este OLES. Este grupo proporcionará no solo continuidad de atención para todas las pacientes, sino también un monitoreo de seguridad mejorado y consistente para las pacientes que participen en el OLES.

Elegibilidad

Edad mínima: 45 YearsSexo: FEMALE

Criterios de inclusión

Women who completed 18 months of treatment in Protocol ALX1-11-93001; or
Women prematurely discontinued from Protocol ALX1-11-93001 who want to participate in OLES for the events listed below must have their clinical course reviewed and approved by the CAB for enrollment into the OLES:
Clinical or incident lumbar vertebral fractures as assessed by the central imaging organization
Clinical or incident hip fracture
Confirmed bone loss at A/P lumbar vertebra or total hip or femoral neck as assessed by the central imaging organization
Body weight below 40 kg
Development of an exclusion criterion in Protocol ALX1-11-93001
It must be accepted by patients whose clinical courses are reviewed by the CAB that participation in OLES may require additional tests at baseline and/or during the study to ensure their utmost safety.
Women with the ability to self-administer a daily injection or have a designee who will give the injections;
Women who are capable of understanding and giving written, voluntary informed consent before the start of open-label dosing with ALX1-11.

Criterios de exclusión

A. History or Concurrent Illness:
Disorders of Immunity Endocrine system Gastrointestinal system Kidney and collecting system Liver, biliary tract and pancreatic systems Musculoskeletal system
Patients with chronic, active joint disease requiring more than one intra-articular injection every 6 months Neoplasia
Patients who have had squamous or basal cell carcinoma of the skin may enter this study if:
The lesion(s) were fully resected with clear margins described in a written report by a pathologist, and
The patient has had no recurrence of lesions for at least one year from the time of the original resection.
Nervous system Vascular, respiratory and cardiac system \*Significant diseases or disorders are determined by history, physical exam or laboratory tests and judged by the Principal Investigator to be significant.
B. Concurrent Medication:
Patients may not use any of the following therapies while they are enrolled in this OLES without permission from the Sponsor and the PMO:
Tetracycline antibiotics for four weeks prior to bone biopsy
Any PTH analogs \[e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs\]
Fluoride
Strontium
Phenytoin for seizure control
Any investigational drug other than ALX1-11
Anabolic steroids or androgens
Active Vitamin D3 metabolites and analogs, e.g., calcitriol
Systemic corticosteroids, more than 5 mg/day prednisone or a systemic corticosteroid formulation equivalent to 5 mg/day prednisone
\. A patient who has been enrolled into the OLES and needs to receive an acute bolus of steroids (oral or injectable) for a self-limited illness may continue treatment in the study if the following requirements are met:
Exposure to steroids will be limited to no more than 30 consecutive days
The maximal dose of steroid (prednisone equivalent) must be limited to no more than 225 mg (7.5 mg each day for 30 days)
The illness is acute in nature and is not expected to recur during the remaining period of the study
Bisphosphonates, including investigational bisphosphonates
Calcitonin
Estrogen replacement therapy by oral, transdermal or intramuscular administration
SERM drugs, e.g., tamoxifen, raloxifene, Evista
Vaginal application of estrogen-containing creams unless the dose is:
conjugated estrogen or estradiol: maximum of 0.5 g twice each week (total of 1.0 g weekly)
Estrace (Ogen): maximum of 1.0 g twice each week (total of 2.0 g weekly)
Daily inhaled corticosteroid unless dose is equivalent to \<1200 µg/day of beclomethasone
Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., remicade \[infliximab\]
Methotrexate
The antimetabolite, methotrexate, which interferes with DNA synthesis, repair and cellular replication should not be used by patients participating in this OLES.
In general, immunomodulatory agents with antiproliferative activity are not permitted as a concomitant medication in this OLES.
Intra-articular injections
\. Patients may receive a maximum of one intra-articular injection (ONE JOINT ONLY) every 6 months while participating in this OLES. The joint that is injected may be a different joint every 6 months. The dose of corticosteroid injected should not exceed the anti-inflammatory equivalent dose of Prednisone 40 mg suspension. The dose and volume should be adjusted downward as appropriate to the size of the joint.
Provera is an acceptable concomitant medication when used according to the label instructions
Patients may be enrolled in this OLES if they have been stabilized on the following therapy for the specified amount of time:
Thyroid Hormone (\<0.1 mg/day thyroxine) therapy for at least 6 months If taking \> 0.1 mg/day but \< 0.2 mg/day, must have serum TSH level 1. \> 0.1mU/L. Patients will be excluded if they are taking doses of \> 0.2 mg/day.
\. However, if a patient has had a minimal change in L-thyroxine dose of \< 0.025 mg/day within 6 months of the baseline visit, and has been on this new dose for at least 2 months, the patient may be enrolled in this study. The patient's history with L-thyroxine must be clearly documented in the source documents.
\. If a patient requires an increase in their thyroid replacement dose, as recommended by a physician who is caring for the patient, after enrollment in this OLES, the patient must have a TSH and T4 level within 3 months of the dose change to ensure the patient does not become hyperthyroid
Stable dosage of thiazide for at least 3 consecutive months
C. Laboratory Values and Physical Examination Findings:
\- Serum calcium greater than 10.7 mg/dL (2.66 mmol/L) at baseline will be managed as outlined in Appendix 4
\- Urinary calcium to creatinine ratio greater than or equal to 1 at baseline will be managed as outlined in Appendix 5
Elevated total serum alkaline phosphates (\> 400 U/L) at baseline will be managed as outlined in Appendix 6 except as noted for Latin and South American countries.
Any other clinically significant abnormal value as judged by the investigator
D. Substance Abuse:
Alcohol and/or drug abuse
E. Compliance:
Suspected or confirmed poor compliance in completing clinical trial evaluations and/or clinical trial required questionnaires

Estudio de extensión abierto de 18 meses sobre la seguridad y eficacia de la hormona paratiroidea humana recombinante, rhPTH(1-84), ALX1-11, en mujeres con osteoporosis posmenopáusica que participaron en el protocolo ALX1-11-93001 (estudio TOP)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

ALX1-11 (drug)

Ubicaciones

'IDIM

'Centro Médico T.I.E.M.P.O

'Hospital Ramos Mejía

'Centro de Osteopatias Medicas

Patrocinadores