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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 March 2022
• Main ID: NCT02284568
• Date of registration: 31/10/2014
• Prospective Registration: Yes
• Primary sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Public title: 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 ARPEGGIO
• Scientific title: A Multinational, Multicenter, Randomized, Double Blind, Parallel Group, Placebo Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Once Daily Oral Administration of Laquinimod (0.6 or 1.5 mg) in Patients With Primary Progressive Multiple Sclerosis (PPMS)
• Date of first enrolment: January 12, 2015
• Target sample size: 374
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02284568
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Canada, Germany, Italy, Netherlands, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Teva Medical Expert, MD
• Affiliation: Teva Branded Pharmaceutical Products R&D, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients must have a confirmed and documented PPMS diagnosis as defined by the 2010
Revised McDonald criteria

2. Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in
either or both brain and spinal cord

3. Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5,
inclusive, at both screening and baseline visits

4. Documented evidence of clinical disability progression in the 2 years prior to
screening.

5. Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait
impairment due to lower extremity dysfunction

6. Patients must be between 25 to 55 years of age, inclusive

7. 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.

8. Patients must sign and date a written informed consent prior to entering the study.

9. Patients must be willing and able to comply with the protocol requirements for the
duration of the study.

Exclusion Criteria:

1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses,
including any episodes of optic neuritis.

2. Progressive neurological disorder other than PPMS.

3. Any MRI record showing presence of cervical cord compression.

4. Baseline MRI showing other findings (including lesions that are atypical for PPMS)
that may explain the clinical signs and symptoms.

5. Relevant history of vitamin B12 deficiency.

6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.

7. Use of experimental or investigational drugs in a clinical study within 24 weeks prior
to baseline. Use of a currently marketed drug in a clinical study within 24 weeks
prior to baseline would not be exclusionary, provided no other exclusion criteria are
met.

8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and
azathioprine within 48 weeks prior to baseline.

9. Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate
(TECFIDERA®, Biogen Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-ß
(either 1a or 1b), intravenous immunoglobulin, or plasmapheresis within 8 weeks prior
to baseline.

10. 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.

11. Prior use of monoclonal antibodies ever, except for:

1. 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)

2. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical
history) is higher than 80 cells/µL

12. 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.

13. Previous use of laquinimod.

14. 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.

15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).

16. Previous total body irradiation or total lymphoid irradiation.

17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of
any kind.

18. Patients who underwent endovascular treatment for chronic cerebrospinal venous
insufficiency (CCSVI) within 12 weeks prior to baseline.

19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to
baseline.

20. Use of inducers of CYP3A4 within 2 weeks prior to baseline.

21. Pregnancy or breastfeeding.

22. Serum levels =3× upper limit of the normal range (ULN) of either alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) at screening.

23. Serum direct bilirubin which is =2×ULN at screening.

24. Patients with a clinically significant or unstable medical or surgical condition that
(in the opinion of the Investigator) would preclude safe and complete study
participation, as determined by medical history, physical examinations,
electrocardiogram (ECG), laboratory tests or chest X-ray.

25. A known history of hypersensitivity to gadolinium (Gd).

26. Glomerular filtration rate (GFR) < or equal 60 mL/min at screening visit.

27. Inability to successfully undergo MRI scanning, including claustrophobia.

28. Known drug hypersensitivity that would preclude administration of laquinimod, such as
hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.



Age minimum: 25 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Progressive Multiple Sclerosis

Intervention(s)

Drug: Laquinimod

Drug: Placebo

Primary Outcome(s)

Percent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48 [Time Frame: Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48]

Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model [Time Frame: Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48 and including early termination visits]

Secondary Outcome(s)

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 [Time Frame: 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 [Time Frame: Baseline (Week 0), Weeks 12, 24, 36, 48]

Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Day 1 up to Week 130 (longest duration of treatment)]

Number of New T2 Brain Lesions at Week 48 [Time Frame: Baseline (Week 0), 48 weeks]

Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48 [Time Frame: Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)]

Secondary ID(s)

2014-001579-30

TV5600-CNS-20006

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 02/11/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02284568