Comparative Clinical Trial to Evaluate Efficacy, Safety and Tolerance of BCD-054 and Avonex® for Treatment of Patients With Remitting-relapsing Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 20 September 2021
• Main ID: NCT02744222
• Date of registration: 03/04/2016
• Prospective Registration: Yes
• Primary sponsor: Biocad
• Public title: Comparative Clinical Trial to Evaluate Efficacy, Safety and Tolerance of BCD-054 and Avonex® for Treatment of Patients With Remitting-relapsing Multiple Sclerosis
• Scientific title: An International Multicenter Double-blind Placebo-controlled Randomized Study to Compare the Efficacy, Safety and Tolerability of BCD-054 (JSC BIOCAD, Russia), 180 µg and 240 µg, Versus Avonex® (Biogen Idec Ltd., UK) in Patients With Relapsing-remitting Multiple Sclerosis
• Date of first enrolment: August 10, 2017
• Target sample size: 399
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02744222
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2/Phase 3

Countries of recruitment

Russian Federation

Contacts

• Name: Roman Ivanov, PhD
• Affiliation: JCS BIOCAD

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed informed consent to participate in the study;

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

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

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

1. At least 1 relapse, or

2. At least 1 Gadolinium enhancing T1-weighted lesion or 1 new T2-weighted lesion in
dynamics.

5. 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,
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)
;

6. Patients of childbearing potential and their partners with preserved reproductive
function must implement reliable contraceptive methods starting from signing informed
consent to 4 weeks after the last dose of study therapy. 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;

7. Total EDSS score of 0 to 5.5 inclusive (assessed by the Assessing Neurologist).

Exclusion Criteria:

1. Primary or secondary progressive MS;

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

3. A relapse during the screening period ;

4. 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;

5. HIV, hepatitis B, hepatitis C, or syphilis ;

6. 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;

7. Baseline leukocyte counts lower than <3.0 × 109/L, platelet counts lower than <125 ×
109/L or hemoglobin levels <100 g/L;

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

9. Signs of clinically significant depression (baseline Beck's score of more than 15);

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

11. Epilepsy;

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

13. A history of use:

- any time before signing informed consent: disease-modifying interferon beta drugs
(interferon beta-1a, interferon beta-1b),

- within 30 days before signing informed consent: glatiramer acetate;

- within 6 months before signing informed consent: monoclonal antibodies, cytotoxic
and/or immunosuppressive drugs, including but not limited to mitoxantrone,
cyclophosphamide, cyclosporine, fingolimod, cladribine; or total lymphoid
irradiation;

14. Systemic (i.v. or oral) corticosteroids used within 30 days before signing informed
consent;

15. A history of intolerance of or allergy to pegylated proteins, interferon beta or other
ingredients of BCD-054/Avonex®;

16. 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 interferon beta-1a or limit treatment compliance;

17. Inability to follow the Protocol procedures (in the Investigator's opinion).

18. 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.

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

20. Vaccination within 4 weeks before signing informed consent (as told by the patient);

21. Participation in other clinical studies within 90 months before signing informed
consent.



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

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Relapsing-Remitting

Intervention(s)

Biological: BCD-054 180 mcg

Biological: BCD-054 240 mcg

Other: Placebo

Biological: Avonex®

Primary Outcome(s)

Time to first relapse after 52 weeks of blinded treatment with BCD-054 or Avonex [Time Frame: Week 52]

Secondary Outcome(s)

Symbol Digit Modalities Test (SDMT) [Time Frame: Week 20, Week 52, Week 104]

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-054 or Avonex® [Time Frame: Week12, Week 20, Week 52, Week 104]

AUC (0-336 hours) [Time Frame: from 0 to 336 hours after the first full dose of BCD-054 or Avonex® (Week 4)]

The proportion of patients who developed AEs/SAEs that, in the Investigator's opinion, are related to BCD-054 or Avonex® [Time Frame: Week12, Week 20, Week 52, Week 104]

AUC (0-168 hours) [Time Frame: from 0 to 168 hours after the first full dose of BCD-054 or Avonex® (Week 4)]

Number of new or enlarging T2-weighted lesions [Time Frame: Week 20, Week 52, Week 104]

AUEC (0-168 hours) [Time Frame: from 0 to 168 hours after the first full dose of BCD-054 or Avonex® (Week 4)]

Changes in hypointense T1-weighted lesion volume [Time Frame: Week 20, Week 52, Week 104]

Changes in T2-weighted lesion volume [Time Frame: Week 20, Week 52, Week 104]

CUA [Time Frame: Week 20, Week 52, Week 104]

Proportion of patients without new or enlarging T2-weighted lesions [Time Frame: Week 20, Week 52, Week 104]

Timed 25-Foot Walk [Time Frame: Week 20, Week 52, Week 104]

AUCss (0-168 hours, 0-336 hours) [Time Frame: from 0 to 168 hours and from 0 to 336 hours since the introduction of 17 injections]

Proportion of relapse-free patients [Time Frame: Week 20, Week 52, Week 104]

The proportion of patients, in each group, who discontinued the study due to AEs/SAEs [Time Frame: Week12, Week 20, Week 52, Week 104]

9-Hole Peg Test (9 HPT) [Time Frame: Week 20, Week 52, Week 104]

Annual average frequency of relapses [Time Frame: Week 20, Week 52, Week 104]

AUEC (0-336 hours) [Time Frame: from 0 to 336 hours after the first full dose of BCD-054 or Avonex® (Week 4)]

AUECss (0-168 hours, 0-336 hours) [Time Frame: from 0 to 168 hours and from 0 to 336 hours after isince the introduction of 17 injections]

Expanded Disability Status Scale (EDSS) [Time Frame: Week 20, Week 52, Week 104]

Proportion of patients with sustained disability progression [Time Frame: Week 20, Week 52, Week 104]

Proportion of patients without contrast-enhancing lesions [Time Frame: Week 20, Week 52, Week 104]

The proportion of BAb- and NAb-positive patients [Time Frame: Week 20, Week 52, Week 104]

Secondary ID(s)

BCD-054-2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors