Zoledronic Acid in MS-patients With Osteoporosis (EXALT)
Primary Purpose
Osteoporosis, Multiple Sclerosis
Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Zoledronic Acid
Placebo
Calcium and Vitamin D combination
Sponsored by
About this trial
This is an interventional treatment trial for Osteoporosis focused on measuring Multiple Sclerosis, Osteoporosis, Zoledronic Acid
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis investigative site
- Novartis Investigative Site
- Novartis investigative site
- Novartis investigative site
- Novartis investigative site
- Novartis investigative site
- Novartis investigative site
- Novartis Investigative Site
- Novartis investigative site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Zoledronic Acid
Placebo
Arm Description
Participants received zoledronic acid infusion in addition to calcium and vitamin D
Participants received placebo to zoledronic acid infusion in addition to calcium and vitamin D
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Adverse Events and Serious Adverse Events Comparison of Treatment Groups
Adverse Events and Serious Adverse events are reported in the safety section.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01166178
Brief Title
Zoledronic Acid in MS-patients With Osteoporosis
Acronym
EXALT
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Terminated
Study Start Date
October 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Multiple Sclerosis
Keywords
Multiple Sclerosis, Osteoporosis, Zoledronic Acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zoledronic Acid
Arm Type
Experimental
Arm Description
Participants received zoledronic acid infusion in addition to calcium and vitamin D
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo to zoledronic acid infusion in addition to calcium and vitamin D
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Intervention Description
Zoledronic acid 5 mg once a year via intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo to zoledronic acid once a year via intravenous infusion
Intervention Type
Dietary Supplement
Intervention Name(s)
Calcium and Vitamin D combination
Intervention Description
Calcium 500 mg and Vitamin D 400 IU combined tablet, taken orally twice a day
Primary Outcome Measure Information:
Title
Change in Bone Mineral Density of the Lumbar Spine at 12 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 12
Title
Change in Bone Mineral Density of the Total Hip Region at 12 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 12
Secondary Outcome Measure Information:
Title
Change in Bone Mineral Density of the Lumbar Spine at 6 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 6
Title
Change in Bone Mineral Density of the Femoral Neck at 6 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 6
Title
Change in Bone Mineral Density of the Total Hip at 6 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 6
Title
Change in Bone Mineral Density of the Femoral Neck at 12 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 12
Title
Change in Bone Mineral Density of the Lumbar Spine at 24 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 24
Title
Change in Bone Mineral Density of the Total Hip Region at 24 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 24
Title
Change in Bone Mineral Density of the Femoral Neck at 24 Months
Description
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.
Time Frame
Screening (day -21 to -1) and month 24
Title
Course of Disease in Multiple Sclerosis Patients
Description
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.
Time Frame
Screening (day -21 to -1) and month 12
Title
Adverse Events and Serious Adverse Events Comparison of Treatment Groups
Description
Adverse Events and Serious Adverse events are reported in the safety section.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bamberg
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigative Site
City
Bochum
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
Country
Germany
Facility Name
Novartis Investigative Site
City
Kassel
Country
Germany
Facility Name
Novartis investigative site
City
Leipzig
Country
Germany
Facility Name
Novartis Investigative Site
City
Leverkusen
Country
Germany
Facility Name
Novartis investigative site
City
Ludwigshafen
Country
Germany
Facility Name
Novartis investigative site
City
Magdeburg
Country
Germany
Facility Name
Novartis investigative site
City
Muenchen
Country
Germany
Facility Name
Novartis investigative site
City
Numbrecht
Country
Germany
Facility Name
Novartis investigative site
City
Oldenburg
Country
Germany
Facility Name
Novartis Investigative Site
City
Siegen
Country
Germany
Facility Name
Novartis investigative site
City
Stade
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Zoledronic Acid in MS-patients With Osteoporosis
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