Back to resultsEfficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders (AQUARELLE) (AQUARELLE)
Primary Purpose
Neuromyelitis Optica Spectrum Disorders
Status
Recruiting
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
divozilimab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Neuromyelitis Optica Spectrum Disorders
Eligibility Criteria
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
Sites / Locations
- Llc "Profimed"Recruiting
- Municipal Autonomous Healthcare Institution of the Order of the Red Banner of Labor "City Clinical Hospital No.1"Recruiting
- Regional Clinical Hospital No.3Recruiting
- Kuzbass Clinical Hospital named after S.V. BelyaevRecruiting
- Khanty-Mansiysk autonomous district - Ugra "The district clinical hospital"Recruiting
- Center for Cardiology and NeurologyRecruiting
- Regional Clinical Hospital № 1 named after Professor S. V. OchapovskyRecruiting
- Moscow Regional Clinical Research Institute named after M.F. Vladimirsky (MONIKI)Recruiting
- Semashko Regional Clinical HospitalRecruiting
- LLC "Medis"Recruiting
- State Novosibirsk Regional Clinical HospitalRecruiting
- Pyatigorsk City Clinical Hospital No.2Recruiting
- Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University"Recruiting
- Pavlov First Saint Petersburg State Medical UniversityRecruiting
- Seredavin Regional Clinical HospitalRecruiting
- Republican Clinical Hospital No.4Recruiting
- Siberian State Medical UniversityRecruiting
- Medical and Sanitary Unit "Neftyanik"Recruiting
- Ulyanovsk Regional Clinical HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BCD-132 (divozilimab)
Placebo
Arm Description
Stage 1 and 2 - Intravenous infusion of BCD-132 every 24 weeks
Stage 1 - Intravenous infusion of Placebo; Stage 2 - Intravenous infusion of BCD-132
Outcomes
Primary Outcome Measures
Time to the first adjudicated relapse within the first 24 weeks of the studу
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
Secondary Outcome Measures
Adjudicated annualized relapse rate
Adjudicated annualized relapse rate
Proportion of subjects without adjudicated relapses
Proportion of subjects without adjudicated relapses at week 24 and 48
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.
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
Vision acuity change
Vision acuity change at Week 24 relative to baseline
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.
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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05730699
Brief Title
Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders (AQUARELLE)
Acronym
AQUARELLE
Official Title
A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 12, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
April 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocad
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromyelitis Optica Spectrum Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
105 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BCD-132 (divozilimab)
Arm Type
Experimental
Arm Description
Stage 1 and 2 - Intravenous infusion of BCD-132 every 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Stage 1 - Intravenous infusion of Placebo; Stage 2 - Intravenous infusion of BCD-132
Intervention Type
Biological
Intervention Name(s)
divozilimab
Intervention Description
anti-CD20 monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Time to the first adjudicated relapse within the first 24 weeks of the studу
Description
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
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Adjudicated annualized relapse rate
Description
Adjudicated annualized relapse rate
Time Frame
Week 52
Title
Proportion of subjects without adjudicated relapses
Description
Proportion of subjects without adjudicated relapses at week 24 and 48
Time Frame
Weeks 24, 48
Title
Change in the Expanded Disability Status Scale (EDSS) score
Description
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.
Time Frame
Week 24
Title
Proportion of subjects with confirmed increase in disability
Description
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
Time Frame
Weeks 24, 26, 48, 52
Title
Vision acuity change
Description
Vision acuity change at Week 24 relative to baseline
Time Frame
Week 24
Title
Change in the Timed 25-Foot (7.62 m) Walk (T25-FW) test
Description
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.
Time Frame
Up to week 48
Title
Changes in the severity of pain using a Numeric Rating Scale
Description
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.
Time Frame
Week 4, 24
Title
Change in the quality of life using a SF-36
Description
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.
Time Frame
Week 24, 52
Title
CUA
Description
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
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anastasiia Porozova
Phone
+7 (812) 380 49 33
Email
porozovaaa@biocad.ru
Facility Information:
Facility Name
Llc "Profimed"
City
Barnaul
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Inna V Smagina
Phone
+7 (3852) 53 74 36
Email
proffmed@mail.ru
Facility Name
Municipal Autonomous Healthcare Institution of the Order of the Red Banner of Labor "City Clinical Hospital No.1"
City
Chelyabinsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diana F Khayrutdinova
Phone
+7 (351) 728 49 99
Email
gkb1.oo@yandex.ru
Facility Name
Regional Clinical Hospital No.3
City
Chelyabinsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Larisa V Lukyanchikova
Phone
+7 (351) 749 99 42
Email
okb3@okb3-74.ru
Facility Name
Kuzbass Clinical Hospital named after S.V. Belyaev
City
Kemerovo
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yelena G Arefeva
Phone
+7 (3842) 396 396
Email
05-guz-kokb@kuzdrav.ru
Facility Name
Khanty-Mansiysk autonomous district - Ugra "The district clinical hospital"
City
Khanty-Mansiysk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ludmila I Anishenko
Phone
+7 (3467) 390 002
Email
hospital@okbhmao.ru
Facility Name
Center for Cardiology and Neurology
City
Kirov
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vyacheslav A Dudin
Phone
+7 (8332) 56 18 61
Email
ckn@medkirov.ru
Facility Name
Regional Clinical Hospital № 1 named after Professor S. V. Ochapovsky
City
Krasnodar
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marianna A Barabanova
Phone
+7 (861) 252 85 00
Email
kkb1@mail.ru
Facility Name
Moscow Regional Clinical Research Institute named after M.F. Vladimirsky (MONIKI)
City
Moscow
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sergey V Kotov
Phone
+7 (499) 674 07 09
Email
moniki@monikiweb.ru
Facility Name
Semashko Regional Clinical Hospital
City
Nischni Nowgorod
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yelena V Parshina
Phone
+7 (831) 438 95 29
Email
official@semashko.nnov.ru
Facility Name
LLC "Medis"
City
Nizhny Novgorod
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irina A Sokolova
Phone
+7 (831) 215 20 00
Email
info@medisnn.ru
Facility Name
State Novosibirsk Regional Clinical Hospital
City
Novosibirsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denis S Korobko
Phone
+7 (383) 315 97 97
Email
gnokb@oblmed.nsk.ru
Facility Name
Pyatigorsk City Clinical Hospital No.2
City
Pyatigorsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gennady N Mishin
Phone
+7 (8793) 98 49 57
Email
email@pgb2.ru
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University"
City
Rostov-on-Don
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zoya A Goncharova
Phone
+7 (863) 285 32 13
Email
okt@rostgmu.ru
Facility Name
Pavlov First Saint Petersburg State Medical University
City
Saint Petersburg
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalya A Totolyan
Phone
+7 (812) 338 78 95
Email
info@1spbgmu.ru
Facility Name
Seredavin Regional Clinical Hospital
City
Samara
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irina YE Poverennova
Phone
+7 (846) 956 12 15
Email
06002@mail.miac.samregion.ru
Facility Name
Republican Clinical Hospital No.4
City
Saransk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikolay V Dorogov
Phone
+7 (8342) 33 42 22
Email
gbuz.rm.rkb.4@e-mordovia.ru
Facility Name
Siberian State Medical University
City
Tomsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valentina M Alifirova
Phone
+7 (800) 250 54 43
Email
rector@ssmu.ru
Facility Name
Medical and Sanitary Unit "Neftyanik"
City
Tyumen
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stella A Siverceva
Phone
+7 (3452) 46 32 91
Facility Name
Ulyanovsk Regional Clinical Hospital
City
Ulyanovsk
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irina V Greshnova
Phone
+7 (8422) 73 77 87
Email
info@uokb.ru
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders (AQUARELLE)
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