Relapsing-remitting Multiple SclerosisPhase 2NCT00879658
Safety, Tolerability, Efficacy and Optimal Dose Finding Study of BAF312 in Patients With Relapsing-remitting Multiple Sclerosis
A Phase 2 study testing BAF312 in people with Relapsing-remitting Multiple Sclerosis, run by Novartis Pharmaceuticals at 72 sites in 12 countries.
Trial summary
The purpose of this study was to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing-remitting Multiple Sclerosis
- What is being tested?
- BAF312
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 297 participants
- Where
- 72 sitesin 12 countries
- Study dates
- 30 Mar 2009to 4 May 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of Multiple Sclerosis (MS) as defined by revised McDonald criteria.
- A relapsing-remitting course of disease with at least 1 documented relapse during the previous year, or 2 documented relapses during the previous 2 years, or a positive gadolinium (Gd)-enhanced MRI scan at screening (in case the first MRI scan obtained at screening is negative, a second scan may be obtained 1 month later.)
- An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization.
- Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization.
- Patients who decline initiation or continuation of treatment with available disease modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator.
Who cannot join
- A manifestation of another type of MS than RRMS
- History of chronic disease of the immune system other than MS
- Malignancies, diabetes, significant cardiovascular, pulmonary and hepatic diseases and conditions
- Active infections
Trial locations and contacts
72 sites in 12 countries.
72 sites in 12 countries
United States16 sites
Novartis Investigative Site
Akron, Ohio, 44320
Novartis Investigative Site
Centennial, Colorado, 80112
Novartis Investigative Site
Chicago, Illinois, 60637
Novartis Investigative Site
Cullman, Alabama, 35058
Novartis Investigative Site
Elk Grove Village, Illinois, 60007
Novartis Investigative Site
Grand Rapids, Michigan, 49525
Novartis Investigative Site
Greenville, South Carolina, 29607
Novartis Investigative Site
Miami, Florida, 33136
Novartis Investigative Site
Milwaukee, Wisconsin, 53215
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15213
Novartis Investigative Site
Pompano Beach, Florida, 33060
Novartis Investigative Site
Raleigh, North Carolina, 27607
Novartis Investigative Site
San Francisco, California, 94143
Novartis Investigative Site
Seattle, Washington, 98122
Novartis Investigative Site
Tallahassee, Florida, 32308
Novartis Investigative Site
Tampa, Florida, 33609
Germany9 sites
Novartis Investigative Site
Berlin, 10713
Novartis Investigative Site
Berlin, 13439
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Lengerich, 49525
Novartis Investigative Site
München, 81675
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Wiesbaden, 65191
Russia9 sites
Novartis Investigative Site
Kazan', 420103
Novartis Investigative Site
Moscow, 101990
Novartis Investigative Site
Moscow, 119049
Novartis Investigative Site
Moscow, 121359
Novartis Investigative Site
Moscow, 125367
Novartis Investigative Site
Moscow, 127018
Novartis Investigative Site
Moscow, 129110
Novartis Investigative Site
Saint Petersburg, 190013
Novartis Investigative Site
Saint Petersburg, 197022
Italy6 sites
Novartis Investigative Site
Chieti, CH, 66100
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Montichiari, BS, 25018
Novartis Investigative Site
Roma, RM, 00133
Novartis Investigative Site
Roma, RM, 00152
Novartis Investigative Site
Roma, RM, 00189
Canada5 sites
Novartis Investigative Site
Gatineau, Quebec, J9J 0A5
Novartis Investigative Site
Greenfield Park, Quebec, J4V 2J2
Novartis Investigative Site
Montreal, Quebec, H3A 2B4
Novartis Investigative Site
Ottawa, Ontario, K1H 8L6
Novartis Investigative Site
Vancouver, British Columbia, V6T 1Z3
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Bilbao, Basque Country, 48013
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Seville, Andalusia, 41009
Novartis Investigative Site
Valencia, Valencia, 46026
Turkey (Türkiye)5 sites
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Haseki / Istanbul, 34096
Novartis Investigative Site
Istanbul, 34093
Novartis Investigative Site
Izmir, 35340
Novartis Investigative Site
Kocaeli, 41380
Hungary4 sites
Novartis Investigative Site
Budapest, 1076
Novartis Investigative Site
Budapest, 1145
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Veszprém, H-8200
Switzerland4 sites
Novartis Investigative Site
Basel, 4031
Novartis Investigative Site
Bern, 3010
Novartis Investigative Site
Lugano, 6900
Novartis Investigative Site
Zurich, 8091
Finland3 sites
Novartis Investigative Site
Helsinki, 00930
Novartis Investigative Site
Tampere, FIN-33520
Novartis Investigative Site
Turku, 20520
Norway3 sites
Novartis Investigative Site
Bergen, 5021
Novartis Investigative Site
Drammen, 3004
Novartis Investigative Site
Oslo, 0424
Poland3 sites
Novartis Investigative Site
Lodz, 90-153
Novartis Investigative Site
Lublin, 20-954
Novartis Investigative Site
Warsaw, 02-957
About this study
Official title: A Phase II, Double-blind, Randomized, Multi-center, Adaptive Dose-ranging, Placebo-controlled, Parallel-group Study Evaluating Safety, Tolerability and Efficacy on MRI Lesion Parameters and Determining the Dose Response Curve of BAF312 Given Orally Once Daily in Patients With Relapsing-remitting Multiple Sclerosis.
The purpose of this study was to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study.
Study Design Rationale An adaptive design was chosen to characterize the dose response curve of BAF312. In a first period of study ("Period 1"), three doses of BAF312 and placebo were tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 wereselected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses were kept blinded. The use of Modeling and Simulation allowed to establish the full range and dynamics of the dose-response curve in silico, and hence the definition of the optimal dose for later phase III studies.
Read more
The choice of placebo as treatment control was essential to obtain information on the specific compared to non-specific effects of active treatment and provides the best way of evaluating the efficacy and of assessing the true safety and tolerability profile of BAF312. Short-term placebo exposure (6 (Period 1) or 3 (Period 2) months, respectively) was unlikely to lead to longer term differences in outcomes [Polman, 2008]. The use of an adaptive design strategy contributed to a significant reduction of placebo exposure, both in terms of the number of patients and duration, as compared to conventional trial models.
Patients having completed the study within the protocol might be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Being tested
- BAF312, Placebo
- Keywords
- Multiple Sclerosis (MS), Relapsing-Remitting, Demyelinating Autoimmune Diseases, Disseminated sclerosis, Encephalomyelitis disseminate, Inflammatory disease, Demyelination, Auto-inflammatory disease, Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Demyelinating Diseases, Neuromyelitis Optica, Diffuse Cerebral Sclerosis of Schilder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAF312Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| BAF312 10mg (period 1) | Experimental | Not described Receives: Drug: BAF312 |
| BAF312 2 mg (period 1) | Experimental | Not described Receives: Drug: BAF312 |
| BAF312 0.5 mg (period 1) | Experimental | Not described Receives: Drug: BAF312 |
| BAF312 dose between 0.1 to 8 mg period 2 | Experimental | Not described Receives: Drug: BAF312 |
| BAF312 dose between 0.1 - 8 mg period 2 | Experimental | Not described Receives: Drug: BAF312 |
| Placebo (period 1, 2) | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Responsiveness of BAF312 Based on the Number of Combined Unique Active MRI Lesions (CUAL)
Combined unique active lesions (CUAL) were defined as new gadolinium [Gd]-enhanced lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions.
ED50 is the dose that gives half of the asymptotic maximum change over placebo. ED90 is the dose that gives 90% of the asymptotic maximum change over placebo.
Measured: 3 months of treatment
Secondary outcomes (15)
Number of Confirmed Relapses - Period 1
confirmed relapse: A relapse was to be confirmed by the Independent Evaluating Physician (examining neurologist) performing the EDSS. It was recommended that this occurred within 7 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the Expanded Disability Status Scale (EDSS) or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS).
Measured: 6 months
Proportion of Participants With Relapse-free Patients - Period 1 + 2
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
Measured: 3 month
Proportion of Participants With Relapse-free Patients - Period 1 Only
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
Measured: 6 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 +2 at Month 3
Results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan. The number of lesions of each type was available from the central MRI reader. No derivation was performed. Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 3 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 Only at 6 Months
Month 4 through Month 6 include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 6 months
Number of All New Gd-enhanced T1 Lesions - Period 1 +2 at Month 3
The results for Month 1 through Month 3 includes patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 3 months
Number of All Gd-enhanced T1 Lesions - Period 1 Only at 6 Months
The results for Month 4 through Month 6 inclusive includes patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 6 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 +2 at 3 Months
The results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 3 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 Only at 6 Months
Month 4 through Month 6 inclusive include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 6 months
Number of Patients Without Any New MRI Disease Activity - Period 1 +2
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
Measured: 3 months
Number of Patients Without Any New MRI Disease Activity - Period 1 Only
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
Measured: 6 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 +2 at 3 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 3.
High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available as such from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 3 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 Only at 6 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 6. High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Measured: 6 months
Number of CUAL - Period 1
Combined unique active lesions (CUAL) are defined as new Gd-enhanced T1 lesions or new or enlarging T2 lesions, withput double counting of lesions at any specific point in time.
Measured: 6 months
Geometric Mean BAF312 Plasma Trough Concentrations
Geometric mean BAF312 plasma concentrations by treatment and by visit
Measured: Month 1, Month 3, Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2009 (estimated)
- Study start30 Mar 2009
- Primary completion4 May 2011
- Study completion4 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsing-remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 297 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00879658
- Sponsor's protocol ID
- CBAF312A2201
- Other IDs
- 2008-008719-25, 2008
- Status last verified
- Dec 2019
- First submitted
- 9 Apr 2009
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Mercier F, Bornkamp B, Ohlssen D, Wallstroem E. Characterization of dose-response for count data using a generalized MCP-Mod approach in an adaptive dose-ranging trial. Pharm Stat. 2015 Jul-Aug;14(4):359-67. doi: 10.1002/pst.1693. Epub 2015 Jun 17.
PubMed 26083135Selmaj K, Li DK, Hartung HP, Hemmer B, Kappos L, Freedman MS, Stuve O, Rieckmann P, Montalban X, Ziemssen T, Auberson LZ, Pohlmann H, Mercier F, Dahlke F, Wallstrom E. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013 Aug;12(8):756-67. doi: 10.1016/S1474-4422(13)70102-9. Epub 2013 Jun 11.
PubMed 23764350
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-blind, Randomized, Multi-center, Adaptive Dose-ranging, Placebo-controlled, Parallel-group Study Evaluating Safety, Tolerability and Efficacy on MRI Lesion Parameters and Determining the Dose Response Curve of BAF312 Given Orally Once Daily in Patients With Relapsing-remitting Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT00879658
- Acronym / sponsor ID
- CBAF312A2201
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Keywords
- Multiple Sclerosis (MS), Relapsing-Remitting, Demyelinating Autoimmune Diseases, Disseminated sclerosis, Encephalomyelitis disseminate, Inflammatory disease, Demyelination, Auto-inflammatory disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 297 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Mar 2009 (actual)
- Primary completion
- 4 May 2011 (actual)
- Study completion
- 4 May 2011 (actual)
- First posted
- 10 Apr 2009 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study.
Study Design Rationale An adaptive design was chosen to characterize the dose response curve of BAF312. In a first period of study ("Period 1"), three doses of BAF312 and placebo were tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 wereselected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses were kept blinded. The use of Modeling and Simulation allowed to establish the full range and dynamics of the dose-response curve in silico, and hence the definition of the optimal dose for later phase III studies.
The choice of placebo as treatment control was essential to obtain information on the specific compared to non-specific effects of active treatment and provides the best way of evaluating the efficacy and of assessing the true safety and tolerability profile of BAF312. Short-term placebo exposure (6 (Period 1) or 3 (Period 2) months, respectively) was unlikely to lead to longer term differences in outcomes [Polman, 2008]. The use of an adaptive design strategy contributed to a significant reduction of placebo exposure, both in terms of the number of patients and duration, as compared to conventional trial models.
Patients having completed the study within the protocol might be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| BAF312 10mg (period 1) | Experimental | Drug: BAF312 |
| BAF312 2 mg (period 1) | Experimental | Drug: BAF312 |
| BAF312 0.5 mg (period 1) | Experimental | Drug: BAF312 |
| BAF312 dose between 0.1 to 8 mg period 2 | Experimental | Drug: BAF312 |
| BAF312 dose between 0.1 - 8 mg period 2 | Experimental | Drug: BAF312 |
| Placebo (period 1, 2) | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Diagnosis of Multiple Sclerosis (MS) as defined by revised McDonald criteria.
- A relapsing-remitting course of disease with at least 1 documented relapse during the previous year, or 2 documented relapses during the previous 2 years, or a positive gadolinium (Gd)-enhanced MRI scan at screening (in case the first MRI scan obtained at screening is negative, a second scan may be obtained 1 month later.)
- An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization.
- Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization.
- Patients who decline initiation or continuation of treatment with available disease modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator.
Key exclusion criteria (4 listed)
- A manifestation of another type of MS than RRMS
- History of chronic disease of the immune system other than MS
- Malignancies, diabetes, significant cardiovascular, pulmonary and hepatic diseases and conditions
- Active infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAF312 | Drug | BAF312 0.5 mg (period 1), BAF312 10mg (period 1), BAF312 2 mg (period 1), BAF312 dose between 0.1 - 8 mg period 2, BAF312 dose between 0.1 to 8 mg period 2 |
| Placebo | Drug | Placebo (period 1, 2) |
Primary outcome
Dose Responsiveness of BAF312 Based on the Number of Combined Unique Active MRI Lesions (CUAL)
Time frame: 3 months of treatment
Combined unique active lesions (CUAL) were defined as new gadolinium [Gd]-enhanced lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions. ED50 is the dose that gives half of the asymptotic maximum change over placebo. ED90 is the dose that gives 90% of the asymptotic maximum change over placebo.
15 secondary outcomes
Number of Confirmed Relapses - Period 1
Time frame: 6 months
Proportion of Participants With Relapse-free Patients - Period 1 + 2
Time frame: 3 month
Proportion of Participants With Relapse-free Patients - Period 1 Only
Time frame: 6 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 +2 at Month 3
Time frame: 3 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 Only at 6 Months
Time frame: 6 months
Number of All New Gd-enhanced T1 Lesions - Period 1 +2 at Month 3
Time frame: 3 months
Number of All Gd-enhanced T1 Lesions - Period 1 Only at 6 Months
Time frame: 6 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 +2 at 3 Months
Time frame: 3 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 Only at 6 Months
Time frame: 6 months
Number of Patients Without Any New MRI Disease Activity - Period 1 +2
Time frame: 3 months
Number of Patients Without Any New MRI Disease Activity - Period 1 Only
Time frame: 6 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 +2 at 3 Months
Time frame: 3 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 Only at 6 Months
Time frame: 6 months
Number of CUAL - Period 1
Time frame: 6 months
Geometric Mean BAF312 Plasma Trough Concentrations
Time frame: Month 1, Month 3, Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26083135Mercier F, Bornkamp B, Ohlssen D, Wallstroem E. Characterization of dose-response for count data using a generalized MCP-Mod approach in an adaptive dose-ranging trial. Pharm Stat. 2015 Jul-Aug;14(4):359-67. doi: 10.1002/pst.1693. Epub 2015 Jun 17.
- Derived from this study: PubMed 23764350Selmaj K, Li DK, Hartung HP, Hemmer B, Kappos L, Freedman MS, Stuve O, Rieckmann P, Montalban X, Ziemssen T, Auberson LZ, Pohlmann H, Mercier F, Dahlke F, Wallstrom E. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013 Aug;12(8):756-67. doi: 10.1016/S1474-4422(13)70102-9. Epub 2013 Jun 11.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
72 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BAF312 in people with Relapsing-remitting Multiple Sclerosis, run by Novartis Pharmaceuticals at 72 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States, Germany, Russia, Italy, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Responsiveness of BAF312 Based on the Number of Combined Unique Active MRI Lesions (CUAL) (time frame: 3 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00879658, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.