A Phase 2 Clinical Study in Subjects With Primary Progressive Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Two Oral Doses of Laquinimod Either of 0.6 mg/Day or 1.5mg/Day (Experimental Drug) as Compared to Placebo

NCT02284568 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TV5600-CNS-200062014-001579-30
• Study Type: interventional
• Target: 374
• Locations: 10 countries
• Sites: 99

Brief Summary

This Phase 2 study is intended to serve as a proof of concept for potential treatment with laquinimod in patients with PPMS. The study is also aimed at evaluating 2 doses of laquinimod in this population.

Conditions

Primary Progressive Multiple Sclerosis

Keywords

multiple sclerosis; primary progressive multiple sclerosis; oral immunomodulator

Outcome Measures

Primary Outcomes (2)

• Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model

  Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. BA was analyzed using baseline-adjusted repeated measures analysis of covariance (ANCOVA- SAS® PROC MIXED) in which 1 contrast was constructed in order to compare between laquinimod 0.6 mg and placebo. The statistical model was a repeated measures analysis of covariance with treatment group, week, treatment group by week interaction, normalized brain volume at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects. Only on-treatment observations (include all the assessments done up to one month after the last dose of the study drug) were included. Values are adjusted means. The cancelled laquinimod 1.5 mg treatment arm was not included in the repeated measures ANCOVA model analysis. However PBVC by visit data are offered in outcome #2.

  Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48 and including early termination visits

• Percent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48

  Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. Early termination scans of participants who discontinued the study after week 36 are considered scans at week 48.

  Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48

Secondary Outcomes (5)

• Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48

  Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)

• Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 48

  Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)

• Change From Baseline for the Timed 25-foot Walk (T25FW) Score at Weeks 12, 24, 36 and 48

  Baseline (Week 0), Weeks 12, 24, 36, 48

• Number of New T2 Brain Lesions at Week 48

  Baseline (Week 0), 48 weeks

• Participants With Treatment-Emergent Adverse Events (TEAEs)

  Day 1 up to Week 130 (longest duration of treatment)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

once daily oral dose

Drug: Placebo

Laquinimod 0.6 mg

EXPERIMENTAL

1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.

Drug: Laquinimod; Drug: Placebo

Laquinimod 1.5 mg

EXPERIMENTAL

3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.

Drug: Laquinimod

Interventions

Placebo DRUG

Placebo

Placebo

Laquinimod DRUG

Laquinimod capsules in 0.5 mg and 0.6 mg strengths

Also known as: TV-5600

Laquinimod 0.6 mg; Laquinimod 1.5 mg

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients must have a confirmed and documented PPMS diagnosis as defined by the 2010 Revised McDonald criteria
• Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord
• Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both screening and baseline visits
• Documented evidence of clinical disability progression in the 2 years prior to screening.
• Functional System Score (FSS) of \> or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction
• Patients must be between 25 to 55 years of age, inclusive
• Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered.
• Patients must sign and date a written informed consent prior to entering the study.
• Patients must be willing and able to comply with the protocol requirements for the duration of the study.

You may not qualify if:

• Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
• Progressive neurological disorder other than PPMS.
• Any MRI record showing presence of cervical cord compression.
• Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
• Relevant history of vitamin B12 deficiency.
• Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
• Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine within 48 weeks prior to baseline.
• Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-β (either 1a or 1b), intravenous immunoglobulin, or plasmapheresis within 8 weeks prior to baseline.
• Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline.
• Prior use of monoclonal antibodies ever, except for:
• natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the patient is John Cunningham (JC) virus antibody test negative (as per medical history)
• rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than 80 cells/μL
• Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone \>5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose.
• Previous use of laquinimod.
• Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (99)

Teva Investigational Site 12966

Phoenix, Arizona, 85018, United States

Location

Teva Investigational Site 12967

Newport Beach, California, 92663, United States

Location

Teva Investigational Site 12962

San Francisco, California, 94158, United States

Location

Teva Investigational Site 12964

Aurora, Colorado, 80045, United States

Location

Teva Investigational Site 12973

Northbrook, Illinois, 60062, United States

Location

Teva Investigational Site 12975

Kansas City, Kansas, 66160-7314, United States

Location

Teva Investigational Site 12969

Lenexa, Kansas, 66214, United States

Location

Teva Investigational Site 12977

Golden Valley, Minnesota, 55422, United States

Location

Teva Investigational Site 13010

Golden Valley, Minnesota, 55422, United States

Location

Teva Investigational Site 12965

Chesterfield, Missouri, 63017, United States

Location

Teva Investigational Site 12968

St Louis, Missouri, 63110, United States

Location

Teva Investigational Site 12963

New York, New York, 10016, United States

Location

Teva Investigational Site 12971

Charlotte, North Carolina, 28207, United States

Location

Teva Investigational Site 12976

Columbus, Ohio, 43221, United States

Location

Teva Investigational Site 12970

Uniontown, Ohio, 44685, United States

Location

Teva Investigational Site 11089

Calgary, AL, T2N 4Z1, Canada

Location

Teva Investigational Site 11084

Halifax, Nova Scotia, B3H 4K4, Canada

Location

Teva Investigational Site 11081

Ottawa, Ontario, K1H 8L6, Canada

Location

Teva Investigational Site 11087

Toronto, Ontario, M5B-1W8, Canada

Location

Teva Investigational Site 11082

Montreal, Quebec, H3A 2B4, Canada

Location

Teva Investigational Site 11088

Québec, Quebec, G1J 1Z4, Canada

Location

Teva Investigational Site 32505

Bad Mergentheim, 97980, Germany

Location

Teva Investigational Site 32512

Bamberg, 96049, Germany

Location

Teva Investigational Site 32510

Berlin, 10117, Germany

Location

Teva Investigational Site 32522

Bochum, 44791, Germany

Location

Teva Investigational Site 32509

Dresden, 01307, Germany

Location

Teva Investigational Site 32517

Düsseldorf, 40225, Germany

Location

Teva Investigational Site 32543

Goettigen, 37075, Germany

Location

Teva Investigational Site 32514

Hamburg, 20099, Germany

Location

Teva Investigational Site 32507

Hanover, 30625, Germany

Location

Teva Investigational Site 32513

München, 81675, Germany

Location

Teva Investigational Site 32504

München, D-81377, Germany

Location

Teva Investigational Site 32516

Rostock, 18057, Germany

Location

Teva Investigational Site 32523

Trier, 54292, Germany

Location

Teva Investigational Site 32503

Ulm, 89081, Germany

Location

Teva Investigational Site 32511

Würzburg, 97080, Germany

Location

Teva Investigational Site 30106

Cefalù, 90015, Italy

Location

Teva Investigational Site 30110

Florence, 50134, Italy

Location

Teva Investigational Site 30105

Gallarate, 21013, Italy

Location

Teva Investigational Site 30108

Genova, 16132, Italy

Location

Teva Investigational Site 30102

Milan, 20127, Italy

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Teva Investigational Site 30107

Orbassano, 10043, Italy

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Teva Investigational Site 30103

Padua, 35128, Italy

Location

Teva Investigational Site 30101

Rome, 00133, Italy

Location

Teva Investigational Site 30104

Rome, ?00152, Italy

Location

Teva Investigational Site 38068

Amsterdam, 1081 HV, Netherlands

Location

Teva Investigational Site 38067

Nijmegen, 6532 SZ, Netherlands

Location

Teva Investigational Site 38069

Sittard, 6162 BG, Netherlands

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Teva Investigational Site 53262

Bialystok, 15-402, Poland

Location

Teva Investigational Site 53250

Bydgoszcz, 85-795, Poland

Location

Teva Investigational Site 53253

Gdansk, 80-803, Poland

Location

Teva Investigational Site 53257

Katowice, 40-635, Poland

Location

Teva Investigational Site 53258

Katowice, 40-684, Poland

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Teva Investigational Site 53256

Katowice, 40-749, Poland

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Teva Investigational Site 53255

Kielce, 25-726, Poland

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Teva Investigational Site 53260

Lublin, 20-954, Poland

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Teva Investigational Site 53261

Olsztyn, 10-560, Poland

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Teva Investigational Site 53252

Warsaw, 02-957, Poland

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Teva Investigational Site 50285

Kaluga, 248007, Russia

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Teva Investigational Site 50288

Kazan', 420021, Russia

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Teva Investigational Site 50290

Kazan', 420103, Russia

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Teva Investigational Site 50294

Kirov, 610006, Russia

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Teva Investigational Site 50292

Krasnoyarsk, 660022, Russia

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Teva Investigational Site 50287

Moscow, 127018, Russia

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Teva Investigational Site 50291

Nizhny Novgorod, 603126, Russia

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Teva Investigational Site 50286

Novosibirsk, 630007, Russia

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Teva Investigational Site 50295

Perm, 614990, Russia

Location

Teva Investigational Site 50289

Saint Petersburg, 194044, Russia

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Teva Investigational Site 50293

Saint Petersburg, 197022, Russia

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Teva Investigational Site 31108

Barcelona, 08036, Spain

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Teva Investigational Site 31106

Barcelona, 8035, Spain

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Teva Investigational Site 31104

Donostia / San Sebastian, 20014, Spain

Location

Teva Investigational Site 31105

El Palmar, 30120, Spain

Location

Teva Investigational Site 31111

Lleida, 25198, Spain

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Teva Investigational Site 31112

Madrid, 28040, Spain

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Teva Investigational Site 31192

Madrid, 28223, Spain

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Teva Investigational Site 31101

Málaga, 29010, Spain

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Teva Investigational Site 31102

Seville, 41009, Spain

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Teva Investigational Site 31100

Valencia, 46026, Spain

Location

Teva Investigational Site 58158

Dnipropetrovsk, 49005, Ukraine

Location

Teva Investigational Site 58159

Ivano-Frankivsk, 76014, Ukraine

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Teva Investigational Site 58157

Kharkiv, 61068, Ukraine

Location

Teva Investigational Site 58160

Kyiv, ?03110, Ukraine

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Teva Investigational Site 58152

Lutsk, 43005, Ukraine

Location

Teva Investigational Site 58154

Lviv, 79010, Ukraine

Location

Teva Investigational Site 58153

Lviv, 79044, Ukraine

Location

Teva Investigational Site 58156

Zaporizhzhia, 69068, Ukraine

Location

Teva Investigational Site 58150

Zaporizhzhya, 69035, Ukraine

Location

Teva Investigational Site 58151

Zaporizhzhya, 69600, Ukraine

Location

Teva Investigational Site 34190

Bristol, BS10 5NB, United Kingdom

Location

Teva Investigational Site 34188

Edinburgh, EH4 2XU, United Kingdom

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Teva Investigational Site 34189

Exeter, EX2 5DW, United Kingdom

Location

Teva Investigational Site 34182

Liverpool, L9 7LJ, United Kingdom

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Teva Investigational Site 34181

London, E1 2AT, United Kingdom

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Teva Investigational Site 34183

Nottingham, NG7 2UH, United Kingdom

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Teva Investigational Site 34184

Oxford, OX3 9DU, United Kingdom

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Teva Investigational Site 34186

Plymouth, PL6 8DH, United Kingdom

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Teva Investigational Site 34185

Stoke-on-Trent, ST4 6GQ, United Kingdom

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Teva Investigational Site 34187

Swansea, SA6 6NL, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36163349 DERIVED

• Giovannoni G, Knappertz V, Steinerman JR, Tansy AP, Li T, Krieger S, Uccelli A, Uitdehaag BMJ, Montalban X, Hartung HP, Pia Sormani M, Cree BAC, Lublin F, Barkhof F. A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis. Neurology. 2020 Aug 25;95(8):e1027-e1040. doi: 10.1212/WNL.0000000000010284. Epub 2020 Jul 10.

  PMID: 32651286 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

laquinimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Pharmaceutical Industries Ltd

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: November 6, 2014
• Study Start: January 12, 2015
• Primary Completion: May 4, 2017
• Study Completion: October 1, 2017
• Last Updated: March 10, 2022
• Results First Posted: November 2, 2018

Record last verified: 2022-03

Locations

US (15); CA (6); UA (10); GB (10); NL (3); ES (10); RU (11); IT (9); PL (10); DE (15)