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Comparative Study of the Efficacy and Safety of BCD-132 With Teriflunomide and Placebo in Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT04056897
Recruitment Status : Active, not recruiting
First Posted : August 14, 2019
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Biocad

Brief Summary:
International multicenter, randomized, double-blind, double-masked, placebo-controlled study of efficacy and safety of BCD-132 (JSC BIOСAD, Russia) using an active reference drug (teriflunomide) for the treatment of patients with multiple sclerosis

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Biological: BCD-132, 125 mg Drug: Teriflunomide Drug: Placebo Biological: BCD-132, 500 mg Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: International Multicenter, Randomized, Double-blind, Double-masked, Placebo-controlled Study of the Efficacy and Safety of BCD-132 Using an Active Reference Drug (Teriflunomide) for the Treatment of Patients With Multiple Sclerosis
Actual Study Start Date : June 7, 2019
Actual Primary Completion Date : July 13, 2020
Estimated Study Completion Date : May 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BCD-132, 125 mg
72 patients
Biological: BCD-132, 125 mg
IV infusion every 24 weeks in combination with placebo tablet daily. The total duration of blinded therapy is 100 weeks (a total of 5 cycles of therapy BCD-132 in combination with a daily placebo)

Experimental: BCD-132, 500 mg
72 patients
Biological: BCD-132, 500 mg
IV infusion every 24 weeks in combination with placebo tablet daily. The total duration of blinded therapy is 100 weeks (a total of 5 cycles of therapy BCD-132 in combination with a daily placebo)

Active Comparator: Teriflunomide
72 patients
Drug: Teriflunomide
14 mg teriflunomide tablet. Per os. Daily in combination with IV placebo. The total duration of blinded therapy is 100 weeks (a total of 5 cycles of placebo IV therapy in combination with daily administration of teriflunomide)

Placebo Comparator: Placebo
54 patients
Drug: Placebo
intravenous infusion in combination with placebo tablet daily. The total duration of blinded therapy is 100 weeks




Primary Outcome Measures :
  1. Number of T1 Gd+ Lesions (per scan) [ Time Frame: week 24 ]
    The number of T1 gadolinium enhancing (T1 Gd+) lesions


Secondary Outcome Measures :
  1. CUA [ Time Frame: week 24, week 100 ]
    The number of combined unique active (CUA) lesions. Changes in MRI (magnetic resonance imaging) markers

  2. Proportion of Patients Without Contrast-enhancing Lesions [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  3. Number of New or Enlarging T2-weighted Lesions [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  4. Number of Patients Without New or Enlarging T2-weighted Lesions [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  5. Changes in T2-weighted Lesion Volume [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  6. Changes in Hypointense T1-weighted Lesion Volume [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  7. Whole-brain Volume Change according MRI [ Time Frame: week 24, week 100 ]
    Changes in MRI markers

  8. Annual Average Frequency of Relapses [ Time Frame: week 24, week 100 ]
    Number of relapses during the year

  9. Time to First Relapse [ Time Frame: week 24, week 100 ]
    Relapse-related variables

  10. Number of Relapse-free Patients [ Time Frame: week 24, week 100 ]
    Relapse-related variables

  11. Number of Patients With Sustained Disability Progression [ Time Frame: week 24, week 100 ]
    Relapse-related variables

  12. Expanded Disability Status Scale (EDSS) [ Time Frame: week 24, week 100 ]
    EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A positive change from baseline indicates improvement

  13. Timed 25-Foot Walk [ Time Frame: week 24, week 100 ]
    Quantitative mobility and leg function performance test based on a timed 25-walk.

  14. 9-Hole Peg Test (9 HPT) [ Time Frame: week 24, week 100 ]
    9HPT is a brief, standardized, quantitative test of upper extremity function

  15. Symbol Digit Modalities Test (SDMT) [ Time Frame: week 24, week 100 ]
    SDMT it is neuropsychological test detecting not only the presence of brain damage, but also changes in cognitive functioning over time and in response to treatment.

  16. 36-Item Short Form Survey (SF-36) [ Time Frame: week 24, week 100 ]
    SF-36 it is a 36-item, patient-reported survey of patient health.The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability

  17. EQ-5D Questionnaire [ Time Frame: week 24, week 100 ]
    EQ-5D - European Quality of Life Questionnaire. It has two components: health state description and evaluation. Rated level can be coded as a number 1, 2, or 3, which indicates having no problems for 1, having some problems for 2, and having extreme problems for 3.

  18. MSQOL-54 Questionnaire [ Time Frame: week 24, week 100 ]

    MSQOL - Multiple Sclerosis Quality of Life-54. Two summary scores - physical health and mental health - can be derived from a weighted combination of scale scores.

    MSQoL-54 has 0-100 scales. Higher values indicate better quality of life.


  19. Number of Patients Who Developed AEs That, in the Investigator's Opinion, Are Related to Treatment [ Time Frame: week 24, week 100 ]
    The Proportion of Patients Who Developed AEs That, in the Investigator's Opinion, Are Related to Treatment

  20. The Number of Patients Who Developed SAEs That, in the Investigator's Opinion, Are Related to Treatment [ Time Frame: week 24, week 100 ]
    SAE- Serious adverse event

  21. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: week 24, week 100 ]
    The Proportion of Patients, in Each Group, Who Developed СТСАЕ v. 5.0 Grade 3-4 AEs That, in the Investigator's Opinion, Are Related to Treatment CTCAE - Common Terminology Criteria for Adverse Events

  22. The Number of Patients, in Each Group, Who Discontinued the Study Due to AEs/SAEs [ Time Frame: week 24, week 100 ]
    AE- adverse event, SAE - serious adverse event

  23. Number of patients with binding and neutralizing antibodies [ Time Frame: week 24, week 100 ]
    The Proportion of binding and neutralizing positive patients

  24. Beck Depression Inventory [ Time Frame: week 24, week 100 ]

    Beck Depression Inventory is a 21-item self-reporting questionnaire for evaluating the severity of depression. Minimum score -0, maximum score - 63.

    Higher total scores indicate more severe depressive symptoms.


  25. C-SSRS [ Time Frame: week 24, week 100 ]

    The Columbia Suicide Severity Rating Scale, or C-SSRS, is a suicidal ideation and behavior rating scale.

    C-SSRS - Columbia-Suicide Severity Rating Scale. Suicidal Ideation Score: The maximum suicidal ideation category (1-5 on the CSSRS) present at the assessment. Assign a score of 0 if no ideation is present.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent to participate in the study;
  2. Men and women aged from 18 to 60 years (inclusive) on the day of signing informed consent;
  3. Confirmed diagnosis of relapsing-remitting multiple sclerosis (according to McDonald criteria 2017 revision);
  4. Documentary evidence that within the last 12 months before signing informed consent the patient had:

    1. At least 1 relapse, or
    2. 2 relapses over the past 2 years, or
    3. At least 1 Gadolinium enhancing T1-weighted lesion and 1 relapse over the past 2 years (24 months) before signing informed consent;
  5. The patient should be neurologically stable during 30 days before signing informed consent (i.e. the patient should not have any new or aggravated neurological symptoms, as told by the patient); or the patient's condition should be completely stabilized since the last relapse, and the duration of stabilization should be at least 30 days);
  6. Total EDSS score of 0 to 5.5 inclusive;
  7. The presence of immunoglobulins G antibodies to the Varicella-Zoster virus according to the results of screening examination;
  8. The absence of suicidal ideation and suicidal behavior established in the screening, according to the C-SSRS score;
  9. The willingness of patients of both sexes and their partners with preserved reproductive function must implement reliable contraceptive methods starting from signing informed consent, throughout the study and within 48 weeks after the last dose of the drug in this study. This requirement does not apply to patients after operative sterilization. Reliable contraception methods include one barrier method in combination with one of the following: spermicides, intrauterine device/oral contraceptives;

Exclusion Criteria:

  1. Primary or secondary progressive MS;
  2. The duration of the MS for more than 10 years with EDSS ≤ 2.0;
  3. Other conditions (except for multiple sclerosis) that can affect the assessment of MS symptoms: to mask, aggravate, change symptoms of multiple sclerosis, result in clinical signs or laboratory instrumental findings suggesting multiple sclerosis;
  4. A relapse during the screening period;
  5. Systemic corticosteroids used within 30 days before signing informed consent;
  6. Diseases requiring prolonged systemic therapy with corticosteroids and / or immunosuppressive drugs, with the exception of MS;
  7. Any acute infections, relapses of chronic infections or any other chronic diseases that are present on the day of signing informed consent and can, as judged by the Investigator, negatively affect the patient's safety during the study treatment;
  8. Congestive heart failure (Grade IV NYHA);
  9. A history of ischemic cerebrovascular disease or spinal cord ischemia, myelopathy, neuromyelitis optica, sarcoidosis;
  10. HIV, hepatitis B, hepatitis C, or syphilis;
  11. Metabolic abnormalities (disorders) manifesting as:

    1. baseline creatinine levels increased more than 2-fold vs. upper limit of normal;
    2. baseline urea levels increased more than 3-fold vs. upper limit of normal;
    3. baseline ALT (Alanine aminotransferase), AST (Aspartate Aminotransferase) or GGT (Gamma-glutamyltransferase) levels increased more than 2.5-fold vs. upper limit of normal;
    4. baseline bilirubin levels increased more than 1.5-fold vs. upper limit of normal;
  12. Baseline leukocyte counts lower than <3.0 × 109/L, platelet counts lower than <125 × 109/L or hemoglobin levels <100 g/L;
  13. TSH (thyroid stimulating hormone) level increased more than 2-fold vs. upper limit of normal;
  14. A history of severe depression, suicidal thoughts or suicide attempts ;
  15. Pregnancy, lactation or planned pregnancy over the entire study period;
  16. A history of use:

    • any time before signing informed consent: anti-B cell therapy drugs (rituximab, oсrelizumab, abatacept, belimumab, ofatumumab and others);
    • any time before signing informed consent: alemtuzumab, daclizumab, teriflunomide, mitoxantrone, cladribine, as well as total lymphatic irradiation (TLI), bone marrow transplantation;
    • within 2 years (24 months) before signing informed consent: cyclophosphamide, cyclosporine, azathioprine; mycophenolate mofetil, fingolimod and sphingosine-1-phosphate (S1P) receptor modulator, natalizumab;
    • immunoglobulin therapy within 30 days before signing informed consent.
  17. Intolerance, including hypersensitivity to any of the components of BCD-132 / teriflunomide, premedication, as well as conditions that, as judged by the Investigator, are a contraindication to the appointment of the above drugs;
  18. The history of severe allergic or anaphylactic reactions;
  19. Progressive multifocal leukoencephalopathy (PML);
  20. Known alcoholic or drug dependency or signs of present alcoholic/drug dependence that, in the Investigator's opinion, can be contraindications for study therapy of MS with anti-CD20 Mab or limit treatment compliance;
  21. Inability to follow the Protocol procedures (in the Investigator's opinion);
  22. Contraindications to MRI or use of gadolinium-containing contrast agents:

    1. Metal foreign objects in the body: magnetic implants, ferromagnetic clips for cerebral vessels, artificial heart valves, electronic middle ear implants, pacemakers;
    2. A history of allergy to gadolinium or gadolinium-containing contrast agents;
    3. Fear of cramped spaces; d) Kidney function impairment with a risk of delayed gadolinium elimination (creatinine level increased to more than 2 x upper limit of normal); d) Documented diagnosis of sickle cell or hemolytic anemia, hemoglobinopathy;
  23. Any malignancies or a history of malignancies, except for cured basal cell carcinoma or cervical cancer in situ;
  24. Vaccination within 4 weeks before signing informed consent (as told by the patient);
  25. Participation in other clinical studies within 90 months before signing informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04056897


Locations
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Russian Federation
State Budgetary Healthcare Institution of Nizhny Novgorod region "Regional Clinical Hospital N.A. Semashko, Nizhny Novgorod"
Nizhny Novgorod, Russian Federation
Sponsors and Collaborators
Biocad
Investigators
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Study Chair: Roman Ivanov, PhD JSC BIOCAD
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Responsible Party: Biocad
ClinicalTrials.gov Identifier: NCT04056897    
Other Study ID Numbers: BCD-132-2
First Posted: August 14, 2019    Key Record Dates
Last Update Posted: February 16, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases