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

Neuromyelitis Optica Spectrum Disorders Clinical Trial

— AQUARELLE  

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05730699
• Other study ID #: BCD-132-6
• Status: Recruiting
• Phase: Phase 3
• Start date: December 12, 2022
• Est. completion date: April 2025

Study information

• Verified date: February 2023
• Source: Biocad
• Contact: Anastasiia Porozova
• Phone: +7 (812) 380 49 33
• Email: porozovaaa[@]biocad.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

BCD-132-6/AQUARELLE is a randomized, double-blind, placebo-controlled phase 3 clinical study in subjects with NMOSD. Eligible subjects will be randomized at a 2:1 ratio to the divozilimab and placebo groups, respectively. At randomization, subjects will be stratified according to the presence of anti-AQP4 antibodies and number of relapses during the past 12 months. Approximately 105 subjects will be enrolled.

The study consists of a screening period, a treatment period (Stage 1 and Stage 2), and a follow-up period.The maximum duration of Stage 1 will be about 24 weeks. During Stage 1, the subjects will receive one dose of the investigational product (divozilimab/placebo). During Stage 2, all subjects (both in the divozilimab and placebo groups) will receive therapy with divozilimab.

The duration of participation for each subject will be approximately 56 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: April 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorders

Intervention

Biological:
• divozilimab
anti-CD20 monoclonal antibody

Drug:
• Placebo
Placebo

Locations

Country	Name	City	State
Russian Federation	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"	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	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

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the first adjudicated relapse within the first 24 weeks of the stud?	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 24
Secondary	Adjudicated annualized relapse rate	Adjudicated annualized relapse rate	Week 52
Secondary	Proportion of subjects without adjudicated relapses	Proportion of subjects without adjudicated relapses at week 24 and 48	Weeks 24, 48
Secondary	Change in the Expanded Disability Status Scale (EDSS) score	Change in the Expanded Disability Status Scale (EDSS) at week 24 relative to baseline.The EDSS ranges from 0 to 10. An increase in EDSS values corresponds to a worsening disability.	Week 24
Secondary	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
Secondary	Vision acuity change	Vision acuity change at Week 24 relative to baseline	Week 24
Secondary	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 48
Secondary	Changes in the severity of pain using a Numeric Rating Scale	Changes in the severity of pain at Week 4 and 24 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
Secondary	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 and 52 relative to baseline. SF-36 (Short Form-36) questionnaire includes a total of 36 questions.	Week 24, 52
Secondary	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