Zoledronic Acid in MS-patients With Osteoporosis

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy and safety of zoledronic acid 5 mg intravenous (i.v.) relative to placebo in Multiple Sclerosis (MS) patients with osteoporosis and to support the optimal use of zoledronic acid for this indication. Primary objective is the change of Bone Mineral Density (BMD) at lumbar spine (L1-L4) and total hip region assessed by T-Score at month 12 relative to screening as measured by Dual X-ray Absorptiometry (DXA). This double-blind period will be followed by a 52-week open-label treatment phase to assess long-term efficacy and safety of zoledronic acid in these patients.

Official Title
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A 1-year, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy of Zoledronic Acid 5 mg (Aclasta®) on Bone Mineral Density in Patients With Multiple Sclerosis Followed by a 1-year Open-label Treatment Phase

Conditions
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Osteoporosis, Multiple Sclerosis

Intervention / Treatment
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* Drug: Zoledronic Acid
* Drug: Placebo
* Dietary Supplement: Calcium and Vitamin D combination


Participation Criteria
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Eligibility Criteria
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Inclusion: Written informed consent to participate in the trial Definite diagnosis of Multiple Sclerosis (MS) as defined by 2005 revised McDonald criteria MS-subtype: Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS), Primary progressive MS (PPMS) Expanded Disability Status Scale (Kurtzke's scale; EDSS) score between 2.5 to 6.5 (including both) Bone mineral density (BMD) T-score of less or equal to -2.0 and more or equal to -4.0 at the lumbar spine (L1-L4 with at least 2 evaluable vertebrae) and/or total hip region and/or femoral neck in recent Dual X-Ray Absorptiometry (DXA)-scan (< or = 3 months) Sufficient ability to read, write and communicate comprehensibly and comply to study procedures No immunomodulatory treatment for MS within the last 30 days or stable and well tolerated therapy with any beta-interferon formulation, or glatirameracetate or fingolimod for at least 30 days immediately prior to baseline Exclusion criteria: Contraindications against Calcium and Vitamin D and zoledronic acid according to the summary product characteristics More than one osteoporotic fracture Concomitant medication with influence on bone mineral density (eg. enzyme- inducing antiepileptics like Carbamazepin, Phenytoin, Phenobarbital, Primidon) Any neurological disorder other than MS which is known to affect bone mineral density (e.g. muscular dystrophy, severe paresis for other reasons than MS, degenerative nervous disorder, stroke) Women who are pregnant or breast feeding, or menstruating and capable of becoming pregnant. Baseline renal insufficiency 25-OH vitamin D level < 10 ng/ml at screening Serum calcium levels > 2.75 mmol/l (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL) at screening Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic Acid<br>Participants received zoledronic acid infusion in addition to calcium and vitamin D | Drug: Zoledronic Acid<br>* Zoledronic acid 5 mg once a year via intravenous infusion<br>Dietary Supplement: Calcium and Vitamin D combination<br>* Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day<br>|
| Placebo Comparator: Placebo<br>Participants received placebo to zoledronic acid infusion in addition to calcium and vitamin D | Drug: Placebo<br>* Placebo to zoledronic acid once a year via intravenous infusion<br>Dietary Supplement: Calcium and Vitamin D combination<br>* Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density of the Lumbar Spine at 12 Months | Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 12 | 
| Change in Bone Mineral Density of the Total Hip Region at 12 Months | Change in bone mineral density (BMD) of the total hip region was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density of the Lumbar Spine at 6 Months | Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 6 | 
| Change in Bone Mineral Density of the Femoral Neck at 6 Months | Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 6 | 
| Change in Bone Mineral Density of the Total Hip at 6 Months | Change in bone mineral density (BMD) of the total hip was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 6. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 6 | 
| Change in Bone Mineral Density of the Femoral Neck at 12 Months | Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 12. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 12 | 
| Change in Bone Mineral Density of the Lumbar Spine at 24 Months | Change in bone mineral density (BMD) of the lumbar spine was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 24 | 
| Change in Bone Mineral Density of the Total Hip Region at 24 Months | Change in bone mineral density (BMD) of the total hip region was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 24 | 
| Change in Bone Mineral Density of the Femoral Neck at 24 Months | Change in bone mineral density (BMD) of the femoral neck was measured using Dual X-ray Absorptiometry (DXA) at screening and at month 24. A DXA scanner is a device that uses x-ray beams to measure the amount of minerals in the bone. | Screening (day -21 to -1) and month 24 | 
| Course of Disease in Multiple Sclerosis Patients | The course of disease in Multiple Sclerosis (MS) patients was measured comparing results from the Expanded Disability Status Scale (EDSS) from screening and month 12. EDSS is a scale, ranging from 0 (normal) to 10 (death due to MS) for assessing neurologic impairment in MS. It is based on a weighting scheme of eight functional systems. The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel&Bladder, Cerebral and Other functions. EDSS was assessed by the treating neurologist. | Screening (day -21 to -1) and month 12 | 
| Adverse Events and Serious Adverse Events Comparison of Treatment Groups | Adverse Events and Serious Adverse events are reported in the safety section. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Osteoporosis, Zoledronic Acid