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

An Open-Label Study of the Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Neuromyelitis Optica Spectrum Disorders
• Intervention / Treatment: Biological: divozilimab

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.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Barnaul, Russian Federation
    • Llc "Profimed"
  • Chelyabinsk, Russian Federation
    • Regional Clinical Hospital No.3
  • Chelyabinsk, Russian Federation
    • Municipal Autonomous Healthcare Institution of the Order of the Red Banner of Labor "City Clinical Hospital No.1"
  • Kemerovo, Russian Federation
    • Kuzbass Clinical Hospital named after S.V. Belyaev
  • Khanty-Mansiysk, Russian Federation
    • Khanty-Mansiysk autonomous district - Ugra "The district clinical hospital"
  • Kirov, Russian Federation
    • Center for Cardiology and Neurology
  • Krasnodar, Russian Federation
    • Regional Clinical Hospital № 1 named after Professor S. V. Ochapovsky
  • Moscow, Russian Federation
    • Moscow Regional Clinical Research Institute named after M.F. Vladimirsky (MONIKI)
  • Nischni Nowgorod, Russian Federation
    • Semashko Regional Clinical Hospital
  • Nizhny Novgorod, Russian Federation
    • LLC "Medis"
  • Novosibirsk, Russian Federation
    • State Novosibirsk regional clinical hospital
  • Pyatigorsk, Russian Federation
    • Pyatigorsk City Clinical Hospital No.2
  • Rostov-on-Don, Russian Federation
    • Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University"
  • Saint Petersburg, Russian Federation
    • Pavlov First Saint Petersburg State Medical University
  • Samara, Russian Federation
    • Seredavin Regional Clinical Hospital
  • Saransk, Russian Federation
    • Republican Clinical Hospital No.4
  • Tomsk, Russian Federation
    • Siberian State Medical University
  • Tyumen, Russian Federation
    • Medical and Sanitary Unit "Neftyanik"
  • Ulyanovsk, Russian Federation
    • Ulyanovsk Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCD-132 (divozilimab); Intravenous infusion of BCD-132 every 24 weeks	Biological: divozilimab; anti-CD20 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjudicated annualized relapse rate [Week 24]	Adjudicated annualized relapse rate	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CUA	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	Week 24
Time to the first adjudicated relapse	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	Week 100
Adjudicated annualized relapse rate	Adjudicated annualized relapse rate	Week 52, 100
Proportion of subjects without adjudicated relapses	Proportion of subjects without adjudicated relapses at week 24, 52, 100	Weeks 24, 52, 100
Change in the Expanded Disability Status Scale (EDSS) score	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.	Week 24, 52, 100
Proportion of subjects with confirmed increase in disability	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	Weeks 24, 26, 48, 52, 100
Vision acuity change	Vision acuity change at Week 24, 52, 100 relative to baseline	Week 24, 52, 100
Change in the Timed 25-Foot (7.62 m) Walk (T25-FW) test	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.	Up to Week 100
Changes in the severity of pain using a Numeric Rating Scale	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.	Week 4, 24, 52, 100
Change in the quality of life using a SF-36	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.	Week 24, 52, 100

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica
• Other Study ID Numbers: BCD-132-6

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No