Dose Escalation Study of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 in Patients With Relapsing-Remitting Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 20 September 2021
• Main ID: NCT03551275
• Date of registration: 13/02/2018
• Prospective Registration: Yes
• Primary sponsor: Biocad
• Public title: Dose Escalation Study of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 in Patients With Relapsing-Remitting Multiple Sclerosis
• Scientific title: A Multicenter Open-Label Non-Comparative Dose Escalation Study (Phase 1) of the Pharmacodynamics, Pharmacokinetics, Safety, and Immunogenicity of BCD-132 (JSC BIOCAD, Russia) in Patients With Relapsing-Remitting Multiple Sclerosis
• Date of first enrolment: February 22, 2018
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03551275
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Factorial Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Russian Federation

Key inclusion & exclusion criteria

Inclusion Criteria:

- Signed written informed consent to participate in the study;

- Men and women aged from 18 to 60 years (inclusive) on the day of signing informed
consent;

- Confirmed diagnosis of relapsing-remitting multiple sclerosis (according to McDonald
criteria 2010);

- Documentary evidence that within the last 12 months before signing informed consent
the patient had:

1. At least one relapse, or

2. At least one gadolinium enhancing T1-weighted lesion or one new T2-weighted
lesion in dynamics.

- 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
during this period, 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);

- A total EDSS score of 0 to 5.5 inclusive (assessed by the Assessing Neurologist);

- Presence of IgG antibodies to varicella zoster virus according to screening results;

- Patients of childbearing potential and their partners with preserved reproductive
function must implement reliable contraceptive methods starting from signing informed
consent and throughout the 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.

- Body weight =65 kg at the screening

- The absence of suicidal ideation and suicidal behavior, as assessed by the C-SSRC
scale, for the period of the 1st month preceding the signing of the informed consent
by the patient (0 score in the evaluation of suicidal ideation and the lack of
positive responses in the section of suicidal behavior) established in the screening.

Exclusion Criteria:

- Primary and secondary progressive multiple sclerosis;

- Multiple sclerosis duration of more than 10 years with EDSS score =2.0 according to
screening results;

- Other conditions (except for multiple sclerosis) that can affect the assessment of
multiple sclerosis symptoms: to mask, aggravate, change symptoms of multiple
sclerosis, result in clinical signs or laboratory instrumental findings suggesting
multiple sclerosis;

- A relapse during the screening period;

- 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;

- HIV, hepatitis B, hepatitis C, or syphilis;

- 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, AST or GGT 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;

- Baseline leukocyte counts lower than <3.0 × 10 9/L, platelet counts lower than <125 ×
10 9/L or hemoglobin levels <100 g/L;

- A history of severe depression, suicidal thoughts or suicide attempts;

- Signs of clinical significant depression (baseline Beck's score of more than 15);

- A history of hypothyroidism/hyperthyroidism and/or baseline abnormalities of TSH
levels vs. lower or upper limits of normal;

- Epilepsy;

- Pregnancy, lactation or planned pregnancy over the entire study period;

- A history of use

1. any time before signing informed consent: anti-B-cell agents (e.g., rituximab,
ocrelizumab, abatacept, belimumab, ofatumumab, etc.);

2. any time before signing informed consent: alemtuzumab, anti-CD4 agents,
daclizumab, teriflunomide, laquinimod, mitoxantrone, cladribine, total lymphatic
irradiation, bone marrow transplant;

3. within 2 years (24 months) before signing informed consent: cyclophosphamide,
cyclosporin, azathioprine; mycophenolate mofetil, fingolimod and other
sphingosine-1-phosphate (S1P) receptor-modulating agents, natalizumab ;

4. therapy with immunoglobulin drug products within 12 weeks before signing informed
consent.

- Systemic corticosteroids used within 30 days before signing informed consent;

- Hypersensitivity to any of BCD-132 ingredients;

- 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 multiple
sclerosis with anti-CD20 monoclonal antibodies or limit treatment compliance;

- Inability to follow the Protocol procedures (in the Investigator's opinion);

- 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;

?) 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); e) Documented diagnosis of sickle cell or hemolytic anemia, hemoglobinopathy.

- Any malignancies or a history of malignancies, except for cured basal cell carcinoma
or cervical cancer in situ;

- Vaccination within 6 weeks before signing informed consent (as told by the patient);

- Participation in other clinical studies within 90 days before signing informed
consent.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Biological: BCD-132

Primary Outcome(s)

The proportion of patients who developed AEs/SAEs that, in the Investigator's opinion, are related to BCD-132 [Time Frame: day 169]

The proportion of patients, in each group, who developed ????? v. 4.03 Grade 3-4 AEs that, in the Investigator's opinion, are related to BCD-132 [Time Frame: day 169]

The proportion of BAb- and NAb-positive patients [Time Frame: day 169]

The proportion of patients, in each group, who discontinued the study due to AEs/SAEs [Time Frame: day 169]

Secondary Outcome(s)

AUEC (0-2016 hours) [Time Frame: day 85, day 169]

AUC (0-2016 hours) [Time Frame: day 85, day 169]

AUEC (0-8) [Time Frame: day 85, day 169]

AUC (0-8) [Time Frame: day 85, day 169]

Secondary ID(s)

BCD-132-1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors