Multiple SclerosisPhase 3BRAVONCT00605215
BRAVO Study: Laquinimod Double-blind Placebo-controlled Study in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) With a Rater Blinded Reference Arm of Interferon β-1a (Avonex®)
A Phase 3 study testing Laquinimod and Avonex® in people with Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc. at 170 sites in 19 countries.
Trial summary
The study aims to compare the effect of daily oral treatment of laquinimod capsules 0.6 milligrams (mg) with the effect of placebo capsules (capsules that contain no active medication) as well as with the effect of an existing Multiple Sclerosis (MS) injectable drug: Interferon β-1a (Avonex®). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Laquinimod and Avonex®
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,331 participants
- Where
- 170 sitesin 19 countries
- Study dates
- 24 Apr 2008to 10 Jun 2011
- Phase
- Phase 3
- 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
- Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
- Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
- Subjects must be in a stable neurological condition between screening (month -1) and baseline visits (month 0).
- Subjects must have had experienced one of the following:
- At least one documented relapse in the 12 months prior to screening
- At least two documented relapses in the 24 months prior to screening
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- One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
- Subjects must be between 18 and 55 years of age, inclusive.
- Subjects must have disease duration of at least 6 months (from first symptom) prior to screening.
- Women of child-bearing potential must practice 2 acceptable methods of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)].
- Subjects must be willing and able to comply with the protocol requirements for the duration of the study.
Who cannot join
- An onset of relapse or any treatment with corticosteroids (intravenous [iv], intramuscular [im] and/or per os [po]) or ACTH between month -1 (screening) and 0 (baseline).
- Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
- Use of immunosuppressive (including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
- Previous use of either of the following: natalizumab (Tysabri®), cladribine or laquinimod.
- Previous treatment with glatiramer acetate (Copaxone®) or IVIG within 3 months prior to screening visit.
- Previous treatment with Interferon beta-1a (Avonex® or Rebif®) or Interferon beta-1b (Betaseron®).
Show all 41Show fewer
- Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit.
- Previous total body irradiation or total lymphoid irradiation.
- Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
- A known history of tuberculosis.
- Acute infection 2 weeks prior to baseline visit.
- Major trauma or surgery 2 weeks prior to baseline visit.
- A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
- A carrier state of factor V Leiden mutation (either homo- or heterozygous) by history or as disclosed at screening.
- Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
- Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (see detailed list of drugs in protocol) (1 month for fluoxetine).
- Use of amiodarone within 2 years prior to screening visit.
- Pregnancy or breastfeeding.
- Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:
- A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
- A gastrointestinal disorder that may affect the absorption of study medication.
- Renal, metabolic, endocrinological or hematological diseases.
- Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
- A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin.
- A QTc interval (obtained from either two ECG recordings at screening or from the mean value calculated from three measurements at baseline visit) which is ≥450msec.
- A family history of Long-QT syndrome.
- A history of drug and/or alcohol abuse.
- Major psychiatric disorder.
- A history of a convulsive disorder.
- Known hypersensitivity to either of the following: mannitol, meglumine or sodium stearyl fumarate.
- Known hypersensitivity that would preclude administration of laquinimod.
- The subject's inability to give informed consent, or to complete the study, or if the subject is considered by the investigator to be, for any reason, an unsuitable candidate for this study.
- A known history of sensitivity to Gadolinium.
- Inability to successfully undergo MRI scanning.
- A known history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation of Avonex®.
- Subjects who suffer from any form of progressive MS
- Any condition which the investigator feels may interfere with participation in the study
- Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation
- Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening
- Previous treatment with immunomodulators within two months prior to screening
- Pregnancy or breastfeeding
Trial locations and contacts
170 sites in 19 countries.
170 sites in 19 countries
United States36 sites
Teva Investigational Site 1261
Akron, Ohio, 44320
Teva Investigational Site 1273
Albany, New York, 12205
Teva Investigational Site 1264
Amherst, New York, 14226
Teva Investigational Site 1275
Atlanta, Georgia, 30309
Teva Investigational Site 1280
Aurora, Colorado, 80045
Teva Investigational Site 1269
Baltimore, Maryland, 21201
Teva Investigational Site 1267
Birmingham, Alabama, 35209
Teva Investigational Site 1241
Canton, Ohio, 44718
Teva Investigational Site 1283
Cedarhurst, New York, 11516
Teva Investigational Site 1245
Cleveland, Ohio, 44195-5244
Teva Investigational Site 1247
Columbus, Ohio, 43221
Teva Investigational Site 1274
Grand Rapids, Michigan, 49525
Teva Investigational Site 1260
Indianapolis, Indiana, 46202
Teva Investigational Site 1239
Lebanon, New Hampshire, 03766
Teva Investigational Site 1268
Lenexa, Kansas, 66214
Teva Investigational Site 1281
Nashville, Tennessee, 37205
Teva Investigational Site 1277
New Orleans, Louisiana, 70115
Teva Investigational Site 1255
Orlando, Florida, 32806
Teva Investigational Site 1272
Pasadena, California, 91105
Teva Investigational Site 1250
Peoria, Illinois, 61603
Teva Investigational Site 1258
Philadelphia, Pennsylvania, 19107
Teva Investigational Site 1237
Phoenix, Arizona, 85013
Teva Investigational Site 1252
Phoenix, Arizona, 85018
Teva Investigational Site 1279
Phoenix, Arizona, 85018
Teva Investigational Site 1244
Portland, Oregon, 97225
Teva Investigational Site 1249
Raleigh, North Carolina, 27607
Teva Investigational Site 1248
Richmond, Virginia, 23298-0599
Teva Investigational Site 1270
Roanoke, Virginia, 24018
Teva Investigational Site 1238
Sacramento, California, 95817
Teva Investigational Site 1284
San Antonio, Texas, 78231
Teva Investigational Site 1282
Sarasota, Florida, 34233
Teva Investigational Site 1263
Shreveport, Louisiana, 71103
Teva Investigational Site 1253
Tacoma, Washington, 98405
Teva Investigational Site 1265
Teaneck, New Jersey, 07666
Teva Investigational Site 1276
Tucson, Arizona, 85741-3537
Teva Investigational Site 1262
Winston-Salem, North Carolina, 27103
Poland18 sites
Teva Investigational Site 5337
Bialystok, 15-402
Teva Investigational Site 5329
Gdansk, 80-803
Teva Investigational Site 5338
Gdansk, 80-952
Teva Investigational Site 4213
Gmina Końskie, 26-200
Teva Investigational Site 6602
Gorzów Wielkopolski, 66-400
Teva Investigational Site 5333
Grodzisk Mazowiecki, 05-825
Teva Investigational Site 5339
Katowice, 40-635
Teva Investigational Site 5334
Katowice, 40-752
Teva Investigational Site 6603
Kielce, 25-736
Teva Investigational Site 5332
Kościerzyna, 83-400
Teva Investigational Site 5345
Krakow, 31-826
Teva Investigational Site 5328
Lodz, 90-153
Teva Investigational Site 5330
Olsztyn, 10-560
Teva Investigational Site 5331
Szczecin, 70-215
Teva Investigational Site 5340
Warsaw, 00-909
Teva Investigational Site 5341
Warsaw, 02-097
Teva Investigational Site 5336
Warsaw, 02-957
Teva Investigational Site 5335
Wroclaw, 50-556
Bulgaria17 sites
Teva Investigational Site 5914
Pleven, 5800
Teva Investigational Site 5915
Pleven, 5800
Teva Investigational Site 5917
Plovdiv, 4000
Teva Investigational Site 4212
Rousse, 7000
Teva Investigational Site 5916
Shumen, 9700
Teva Investigational Site 5920
Sofia, 1000
Teva Investigational Site 5907
Sofia, 1113
Teva Investigational Site 5910
Sofia, 1113
Teva Investigational Site 5909
Sofia, 1309
Teva Investigational Site 5919
Sofia, 1407
Teva Investigational Site 5906
Sofia, 1606
Teva Investigational Site 5908
Sofia, 1606
Teva Investigational Site 5911
Sofia, 1606
Teva Investigational Site 5912
Sofia, 1606
Teva Investigational Site 5918
Stara Zagora, 6000
Teva Investigational Site 5913
Varna, 9010
Teva Investigational Site 4211
Veliko Tarnovo, 5000
Ukraine15 sites
Teva Investigational Site 6503
Chernihiv, 14029
Teva Investigational Site 5823
Chernivtsi, 58018
Teva Investigational Site 5811
Dnipropetrovsk, 49027
Teva Investigational Site 5812
Donetsk, 83003
Teva Investigational Site 5814
Ivano-Frankivsk, 76008
Teva Investigational Site 5817
Kharkiv, 61018
Teva Investigational Site 5818
Kharkiv, 61068
Teva Investigational Site 5815
Kharkiv, 61103
Teva Investigational Site 5822
Kyiv, 03110
Teva Investigational Site 5809
Lviv, 79010
Teva Investigational Site 5820
Odesa, 65025
Teva Investigational Site 5821
Poltava, 36024
Teva Investigational Site 5810
Vinnytsia, 21005
Teva Investigational Site 5819
Zaporizhzhya, 69035
Teva Investigational Site 5816
Zaporizhzhya, 69600
Italy12 sites
Teva Investigational Site 3056
Bologna, 40139
Teva Investigational Site 3062
Catania, 95122
Teva Investigational Site 3053
Cefalù, 90015
Teva Investigational Site 3054
Chieti, 66100
Teva Investigational Site 3061
Empoli, 50053
Teva Investigational Site 3049
Florence, 50139
Teva Investigational Site 3055
Naples, 80131
Teva Investigational Site 3048
Rome, 00133
Teva Investigational Site 3052
Rome, 00149
Teva Investigational Site 3050
Rome, 00168
Teva Investigational Site 3060
Rome, 163
Teva Investigational Site 3051
Torino, 10126
Russia11 sites
Teva Investigational Site 5043
Barnaul, 656024
Teva Investigational Site 5033
Moscow, 117152
Teva Investigational Site 5032
Moscow, 117997
Teva Investigational Site 5041
Moscow, 125367
Teva Investigational Site 5038
Novosibirsk, 630087
Teva Investigational Site 5042
Novosibirsk, 630117
Teva Investigational Site 5036
Saint Petersburg, 194291
Teva Investigational Site 5035
Saint Petersburg, 197022
Teva Investigational Site 5034
Saint Petersburg, 197376
Teva Investigational Site 5037
Samara, 443095
Teva Investigational Site 5044
Ufa, 450007
Germany8 sites
Teva Investigational Site 6701
Bayreuth, 95445
Teva Investigational Site 6703
Berlin, 10117
Teva Investigational Site 6402
Berlin, 12203
Teva Investigational Site 6700
Berlin, 13088
Teva Investigational Site 6702
Dresden, 01307
Teva Investigational Site 6401
Hanover, 30559
Teva Investigational Site 6403
Münster, 48149
Teva Investigational Site 6400
Ulm, 89081
Romania8 sites
Teva Investigational Site 5218
Bucharest, 010825
Teva Investigational Site 5214
Bucharest, 022328
Teva Investigational Site 5213
Bucharest, 050098
Teva Investigational Site 5215
Cluj-Napoca, 400012
Teva Investigational Site 5217
Constanța, 900591
Teva Investigational Site 8209
Craiova, 200515
Teva Investigational Site 5216
Iași, 700661
Teva Investigational Site 5219
Sibiu, 550245
South Africa7 sites
Teva Investigational Site 9007
Bloemfontein, 9301
Teva Investigational Site 9001
Cape Town, 7925
Teva Investigational Site 9004
Johannesburg, 2157
Teva Investigational Site 9003
Johannesburg, 2193
Teva Investigational Site 9008
Pietermaritzburg, 3201
Teva Investigational Site 9005
Pretoria, 0041
Teva Investigational Site 9006
Rosebank, 2196
Spain7 sites
Teva Investigational Site 3147
Barcelona, 08035
Teva Investigational Site 3154
Figueres-Girona, 17600
Teva Investigational Site 3149
L'Hospitalet de Llobregat, 08907
Teva Investigational Site 3152
Madrid, 28041
Teva Investigational Site 3151
Málaga, 29010
Teva Investigational Site 3148
Seville, 41009
Teva Investigational Site 3153
Tortosa-Tarragona, 43500
Croatia6 sites
Teva Investigational Site 6003
Osijek, 31 000
Teva Investigational Site 6004
Split, 21000
Teva Investigational Site 6005
Varaždin, 42000
Teva Investigational Site 6001
Zagreb, 10000
Teva Investigational Site 6002
Zagreb, 10000
Teva Investigational Site 6006
Zagreb, 10000
Czechia5 sites
Teva Investigational Site 5422
Brno, 602 00
Teva Investigational Site 5419
Olomouc, 779 00
Teva Investigational Site 5418
Prague, 128 08
Teva Investigational Site 5420
Praha 5- Motol, 150 06
Teva Investigational Site 5421
Teplice, 415 29
Israel4 sites
Teva Investigational Site 8043
Haifa, 3436212
Teva Investigational Site 8041
Jerusalem, 9112001
Teva Investigational Site 8040
Ramat Gan, 5262160
Teva Investigational Site 8042
Ramat Gan, 5262160
Slovakia4 sites
Teva Investigational Site 6200
Bratislava, 813 69
Teva Investigational Site 6201
Bratislava, 826 06
Teva Investigational Site 6202
Nitra, 949 01
Teva Investigational Site 6203
Žilina, 010 01
Estonia3 sites
Teva Investigational Site 5508
Kohtla-Järve, 31025
Teva Investigational Site 5507
Tallinn, EE-10617
Teva Investigational Site 5509
Tartu, EE-51014
Georgia3 sites
Teva Investigational Site 8102
Tbilisi, 0112
Teva Investigational Site 8104
Tbilisi, 0112
Teva Investigational Site 8103
Tbilisi, 0179
North Macedonia3 sites
Teva Investigational Site 6502
Bitola, 7000
Teva Investigational Site 6500
Skopje, 1000
Teva Investigational Site 6501
Skopje, 1000
Lithuania2 sites
Teva Investigational Site 5708
Kaunas, 50009
Teva Investigational Site 5707
Šiauliai, 76231
About this study
Official title: A Multinational, Multicenter, Randomized, Parallel-Group Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Laquinimod Over Placebo in a Double-blind Design and of a Reference Arm of Interferon β-1a (Avonex®) in a Rater-blinded Design
The study aims to compare the effect of daily oral treatment of laquinimod capsules 0.6 milligrams (mg) with the effect of placebo capsules (capsules that contain no active medication) as well as with the effect of an existing Multiple Sclerosis (MS) injectable drug: Interferon β-1a (Avonex®).
- Conditions
- Multiple Sclerosis
- Being tested
- Laquinimod, Placebo, Avonex®
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LaquinimodDrug
Laquinimod will be administered per dose and schedule specified in the arm description.
PlaceboDrug
Placebo matching to laquinimod will be administered per schedule specified in the arm description.
Avonex®Drug
Also called Interferon β-1a
Avonex® will be administered per dose and schedule specified in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive 1 capsule of placebo matching to laquinimod orally once daily for 24 months. Receives: Drug: Placebo |
| Laquinimod | Experimental | Participants will receive 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. Receives: Drug: Laquinimod |
| Avonex® | Active comparator | Participants will receive an injection of Avonex® 30 micrograms (mcg) given intramuscularly (IM) once weekly for 24 months. Receives: Drug: Avonex® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Rate of Confirmed Relapses
A relapse was defined as the appearance of new neurological abnormalities or the reappearance of previously observed neurological abnormalities; lasting at least 48 hours and immediately preceded by an improved neurological state of ≥30 days from onset of previous relapse, accompanied by observed objective neurological changes (an increase of ≥0.5 in Expanded Disability Status Scale [EDSS] score, or an increase of 1 grade in the score of 2 or more of the 7 Functional Systems [FS], or an increase of 2 grades in the score of 1 FS as compared to the previous evaluation). Total number of confirmed relapses during the treatment period was divided by the sum of number of days on study in the treatment period and then multiplied by the number of days in the year to calculate the annualized relapse rate. Annualized relapse rate was derived from a baseline-adjusted negative binomial regression.
Measured: Baseline up to Month 24
Secondary outcomes (3)
Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score
The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome.
Measured: Baseline, Month 24
Percent Change From Baseline in Brain Volume
Change in brain volume was derived from MRI scans obtained at baseline and at Month 24.
Measured: Baseline, Month 24
Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS
A confirmed progression of EDSS was defined as a 1 point increase from baseline on EDSS score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if baseline EDSS was 5.5, confirmed 3 months later. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). Data is presented as distribution of confirmed progression (number of participants with confirmed progression of EDSS) sustained for 3 months. Progression could not be confirmed during a relapse.
Measured: Baseline up to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2008 (estimated)
- Study start24 Apr 2008
- Primary completion10 Jun 2011
- Study completion10 Jun 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 Multiple SclerosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,331 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Teva Medical Expert, M.D., Study director, Teva Branded Pharmaceutical Products R&D, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00605215
- Sponsor's protocol ID
- MS-LAQ-302
- Other IDs
- 2007-005450-23
- Acronym
- BRAVO
- Status last verified
- Mar 2022
- First submitted
- 8 Jan 2008
- Last updated
- 21 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.
PubMed 36163349Kolb-Sobieraj C, Gupta S, Weinstock-Guttman B. Laquinimod therapy in multiple sclerosis: a comprehensive review. Neurol Ther. 2014 May 6;3(1):29-39. doi: 10.1007/s40120-014-0017-6. eCollection 2014 Jun.
PubMed 26000222
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multinational, Multicenter, Randomized, Parallel-Group Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Laquinimod Over Placebo in a Double-blind Design and of a Reference Arm of Interferon β-1a (Avonex®) in a Rater-blinded Design
- ClinicalTrials.gov ID
- NCT00605215
- Acronym / sponsor ID
- BRAVO / MS-LAQ-302
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,331 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Study start
- 24 Apr 2008 (actual)
- Primary completion
- 10 Jun 2011 (actual)
- Study completion
- 10 Jun 2011 (actual)
- First posted
- 30 Jan 2008 (estimated)
- Results
- Posted 21 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to compare the effect of daily oral treatment of laquinimod capsules 0.6 milligrams (mg) with the effect of placebo capsules (capsules that contain no active medication) as well as with the effect of an existing Multiple Sclerosis (MS) injectable drug: Interferon β-1a (Avonex®).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive 1 capsule of placebo matching to laquinimod orally once daily for 24 months. |
| Laquinimod | Experimental | Drug: LaquinimodParticipants will receive 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. |
| Avonex® | Active comparator | Drug: Avonex®Participants will receive an injection of Avonex® 30 micrograms (mcg) given intramuscularly (IM) once weekly for 24 months. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
- Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
- Subjects must be in a stable neurological condition between screening (month -1) and baseline visits (month 0).
- Subjects must have had experienced one of the following:
- At least one documented relapse in the 12 months prior to screening
Key exclusion criteria (41 listed)
- An onset of relapse or any treatment with corticosteroids (intravenous [iv], intramuscular [im] and/or per os [po]) or ACTH between month -1 (screening) and 0 (baseline).
- Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
- Use of immunosuppressive (including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
- Previous use of either of the following: natalizumab (Tysabri®), cladribine or laquinimod.
- Previous treatment with glatiramer acetate (Copaxone®) or IVIG within 3 months prior to screening visit.
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 |
|---|---|---|
| LaquinimodLaquinimod will be administered per dose and schedule specified in the arm description. | Drug | Laquinimod |
| PlaceboPlacebo matching to laquinimod will be administered per schedule specified in the arm description. | Drug | Placebo |
| Avonex®Also: Interferon β-1aAvonex® will be administered per dose and schedule specified in the arm description. | Drug | Avonex® |
Primary outcome
Annualized Rate of Confirmed Relapses
Time frame: Baseline up to Month 24
A relapse was defined as the appearance of new neurological abnormalities or the reappearance of previously observed neurological abnormalities; lasting at least 48 hours and immediately preceded by an improved neurological state of ≥30 days from onset of previous relapse, accompanied by observed objective neurological changes (an increase of ≥0.5 in Expanded Disability Status Scale [EDSS] score, or an increase of 1 grade in the score of 2 or more of the 7 Functional Systems [FS], or an increase of 2 grades in the score of 1 FS as compared to the previous evaluation). Total number of confirmed relapses during the treatment period was divided by the sum of number of days on study in the treatment period and then multiplied by the number of days in the year to calculate the annualized relapse rate. Annualized relapse rate was derived from a baseline-adjusted negative binomial regression.
3 secondary outcomes
Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score
Time frame: Baseline, Month 24
Percent Change From Baseline in Brain Volume
Time frame: Baseline, Month 24
Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS
Time frame: Baseline up to Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36163349Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.
- Derived from this study: PubMed 26000222Kolb-Sobieraj C, Gupta S, Weinstock-Guttman B. Laquinimod therapy in multiple sclerosis: a comprehensive review. Neurol Ther. 2014 May 6;3(1):29-39. doi: 10.1007/s40120-014-0017-6. eCollection 2014 Jun.
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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.
Teva Medical Expert, M.D. study director
Teva Branded Pharmaceutical Products R&D, Inc.
170 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Laquinimod and Avonex® in people with Multiple Sclerosis, run by Teva Branded Pharmaceutical Products R&D, Inc. at 170 sites in 19 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 11 inclusion and 41 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 21 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 170 sites in United States, Poland, Bulgaria, Ukraine, Italy and 14 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 21 Apr 2022). 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?
Annualized Rate of Confirmed Relapses (time frame: Baseline up to Month 24). 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 NCT00605215, 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 21 Apr 2022.