Zoledronic Acid in MS-patients With Osteoporosis (EXALT)

• ClinicalTrials.gov Identifier: NCT01166178
• Recruitment Status: Terminated
• First Posted: July 20, 2010
• Results First Posted: November 26, 2013
• Last Update Posted: November 26, 2013
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

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.

Condition or disease	Intervention/treatment	Phase
Osteoporosis; Multiple Sclerosis	Drug: Zoledronic Acid; Drug: Placebo; Dietary Supplement: Calcium and Vitamin D combination	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: October 2010
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: June 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Bone Mineral Density of the Lumbar Spine at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ]

   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.

2. Change in Bone Mineral Density of the Total Hip Region at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ]

   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 :

1. Change in Bone Mineral Density of the Lumbar Spine at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ]

   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.

2. Change in Bone Mineral Density of the Femoral Neck at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ]

   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.

3. Change in Bone Mineral Density of the Total Hip at 6 Months [ Time Frame: Screening (day -21 to -1) and month 6 ]
   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.
4. Change in Bone Mineral Density of the Femoral Neck at 12 Months [ Time Frame: Screening (day -21 to -1) and month 12 ]

   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.

5. Change in Bone Mineral Density of the Lumbar Spine at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ]

   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.

6. Change in Bone Mineral Density of the Total Hip Region at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ]

   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.

7. Change in Bone Mineral Density of the Femoral Neck at 24 Months [ Time Frame: Screening (day -21 to -1) and month 24 ]

   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.

8. Course of Disease in Multiple Sclerosis Patients [ Time Frame: Screening (day -21 to -1) and month 12 ]
   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.
9. Adverse Events and Serious Adverse Events Comparison of Treatment Groups [ Time Frame: 24 months ]
   Adverse Events and Serious Adverse events are reported in the safety section.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

Novartis Investigative Site

Bamberg, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Bochum, Germany

Novartis Investigative Site

Hamburg, Germany

Novartis Investigative Site

Heidelberg, Germany

Novartis Investigative Site

Kassel, Germany

Novartis investigative site

Leipzig, Germany

Novartis Investigative Site

Leverkusen, Germany

Novartis investigative site

Ludwigshafen, Germany

Novartis investigative site

Magdeburg, Germany

Novartis investigative site

Muenchen, Germany

Novartis investigative site

Numbrecht, Germany

Novartis investigative site

Oldenburg, Germany

Novartis Investigative Site

Siegen, Germany

Novartis investigative site

Stade, Germany

Sponsors and Collaborators

Novartis

Investigators

• Study Director: Novartis Pharmceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01166178
• Other Study ID Numbers: CZOL446HDE40; 2009-011888-37 ( EudraCT Number )
• First Posted: July 20, 2010
• Results First Posted: November 26, 2013
• Last Update Posted: November 26, 2013
• Last Verified: October 2013

Keywords provided by Novartis:

Multiple Sclerosis; Osteoporosis; Zoledronic Acid

Additional relevant MeSH terms:

Osteoporosis; Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Vitamin D; Zoledronic Acid; Calcium; Vitamins; Micronutrients; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Bone Density Conservation Agents