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Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders (AQUARELLE)

Phase 3
Active, not recruiting
Conditions
Neuromyelitis Optica Spectrum Disorders
Interventions
Biological: divozilimab
Registration Number
NCT05730699
Lead Sponsor
Biocad
Brief Summary

The goal of this clinical trial is to study the efficacy and safety of BCD-132 (divozilimab) in subjects with neuromyelitis optica spectrum disorders (NMOSD).

Detailed Description

BCD-132-6/AQUARELLE is an open-label phase 3 clinical study in subjects with NMOSD. Approximately 105 subjects will be enrolled.

The study consists of a screening period, a treatment period and a follow-up period. During treatment period, the subjects will receive the investigational product divozilimab.

The duration of participation for each subject will be approximately 104 weeks.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
105
Inclusion Criteria
  • NMOSD diagnosed based on the 2015 NMOSD International Consensus Diagnostic Criteria
  • Documented evidence of at least 1 relapse within 12 months before signing the informed consent form, or 2 relapses within 24 months before signing the informed consent form
  • A total EDSS score of ≤ 7
  • Presence of IgG antibodies to the Varicella Zoster virus at screening
  • A CD19+ cell proportion of ≥ 1 % of the total lymphocyte count in patients exposed to other anti-B-cell therapies more than 6 months before signing the informed consent form
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Exclusion Criteria
  • A relapse occurring less than 30 days before signing the informed consent form or at screening (patients may be re-screened)
  • Intrathecal oligoclonal or monoclonal IgG production (in patients who are anti-AQP4 seronegative)
  • Other nervous system disorders (including multiple sclerosis) that can mask or affect the assessment of NMOSD symptoms
  • History of other autoimmune diseases requiring immunosuppressive therapy
  • Prior exposure to: alemtuzumab, total lymphatic irradiation, bone marrow transplantation; anti-B-cell therapy drugs, abatacept, satralizumab within 6 months prior to signing the informed consent form; mitoxantrone, cyclophosphamide, methotrexate, cyclosporine A, tacrolimus, eculizumab, tocilizumab, natalizumab, interferon beta, glatiramer acetate, fingolimod, teriflunomide, dimethyl fumarate within 3 months before signing the informed consent form; immunoglobulin products within 30 days before signing the informed consent form; transfusion of blood or blood components within 30 days before signing the informed consent form; systemic corticosteroids at the time of signing the informed consent form
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BCD-132 (divozilimab)divozilimabIntravenous infusion of BCD-132 every 24 weeks
Primary Outcome Measures
NameTimeMethod
Adjudicated annualized relapse rate [Week 24]Week 24

Adjudicated annualized relapse rate

Secondary Outcome Measures
NameTimeMethod
Time to the first adjudicated relapseWeek 100

Time to the first adjudicated relapse is defined as the time from the date of randomization in the study to the date of the onset of symptoms of the adjudicated relapse. Each relapse will be adjudicated by an independent neurological commission

Adjudicated annualized relapse rateWeek 52, 100

Adjudicated annualized relapse rate

Proportion of subjects without adjudicated relapsesWeeks 24, 52, 100

Proportion of subjects without adjudicated relapses at week 24, 52, 100

Change in the Expanded Disability Status Scale (EDSS) scoreWeek 24, 52, 100

Change in the Expanded Disability Status Scale (EDSS) at week 24, 52, 100 relative to baseline.The EDSS ranges from 0 to 10. An increase in EDSS values corresponds to a worsening disability.

Proportion of subjects with confirmed increase in disabilityWeeks 24, 26, 48, 52, 100

Confirmed increase in disability is defined as an increase in the EDSS score (not related to a previous relapse and assuming there is no relapse at assessment) compared to Day 1 (baseline) by at least 1.5 in subjects with a baseline score of 0; by at least 1.0 in subjects with a baseline score of \> 0 and ≤ 5.5; and by at least 0.5 in subjects with a baseline score of ≥ 6.0 persisting for ≥ 3 months

Vision acuity changeWeek 24, 52, 100

Vision acuity change at Week 24, 52, 100 relative to baseline

Change in the Timed 25-Foot (7.62 m) Walk (T25-FW) testUp to Week 100

Change in the Timed 25-Foot (7.62 m) Walk (T25-FW) test over time compared to baseline.

T25-FW test is a way to quantify lower limb functions. The subject standing at one end of a clearly marked 25-foot (7.62-meter) course is asked to walk the distance as quickly but as safely as possible. After the first attempt, the subject is asked to walk the same distance again. The results (time in seconds) of both attempts are recorded.

Changes in the severity of pain using a Numeric Rating ScaleWeek 4, 24, 52, 100

Changes in the severity of pain at Week 4, 24, 52, 100 relative to baseline. The Numerical Rating Scale (NRS) will be used to assess the intensity of the subject's pain. NRS consists of consecutive numbers from 0 to 10, where 0 is no pain and 10 is the most severe pain that can be imagined.

Change in the quality of life using a SF-36Week 24, 52, 100

Change in the quality of life parameters using a SF-36 questionnaire at week 24, 52, 100 relative to baseline. SF-36 (Short Form-36) questionnaire includes a total of 36 questions.

CUAWeek 24

CUA (Cumulative Total Active) - • Cumulative number of new Gd-enhancing T1-weighted lesions and new T2-weighted lesions or enlarging T2-weighted lesions without double counting

Trial Locations

Locations (19)

Llc "Profimed"

🇷🇺

Barnaul, Russian Federation

Municipal Autonomous Healthcare Institution of the Order of the Red Banner of Labor "City Clinical Hospital No.1"

🇷🇺

Chelyabinsk, Russian Federation

Regional Clinical Hospital No.3

🇷🇺

Chelyabinsk, Russian Federation

Kuzbass Clinical Hospital named after S.V. Belyaev

🇷🇺

Kemerovo, Russian Federation

Khanty-Mansiysk autonomous district - Ugra "The district clinical hospital"

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Khanty-Mansiysk, Russian Federation

Center for Cardiology and Neurology

🇷🇺

Kirov, Russian Federation

Regional Clinical Hospital № 1 named after Professor S. V. Ochapovsky

🇷🇺

Krasnodar, Russian Federation

Moscow Regional Clinical Research Institute named after M.F. Vladimirsky (MONIKI)

🇷🇺

Moscow, Russian Federation

Semashko Regional Clinical Hospital

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Nischni Nowgorod, Russian Federation

LLC "Medis"

🇷🇺

Nizhny Novgorod, Russian Federation

State Novosibirsk Regional Clinical Hospital

🇷🇺

Novosibirsk, Russian Federation

Pyatigorsk City Clinical Hospital No.2

🇷🇺

Pyatigorsk, Russian Federation

Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University"

🇷🇺

Rostov-on-Don, Russian Federation

Pavlov First Saint Petersburg State Medical University

🇷🇺

Saint Petersburg, Russian Federation

Seredavin Regional Clinical Hospital

🇷🇺

Samara, Russian Federation

Republican Clinical Hospital No.4

🇷🇺

Saransk, Russian Federation

Siberian State Medical University

🇷🇺

Tomsk, Russian Federation

Medical and Sanitary Unit "Neftyanik"

🇷🇺

Tyumen, Russian Federation

Ulyanovsk Regional Clinical Hospital

🇷🇺

Ulyanovsk, Russian Federation

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