Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an open label, phase 1, "3+3" dose escalating study of tolerability, safety, pharmacokinetics and immunogenicity of a single subcutaneous injection of the novel monoclonal antibody against human IL-17 - BCD-085. The study will enroll 37 healthy male volunteers.
IL-17 is a new potential therapeutic target which plays important role in pathogenesis of several autoimmune disorders including psoriasis, rheumatoid arthritis, possibly - SLE and MS. BCD-085 is a novel humanized monoclonal antibody against human IL17 developed by JCS BIOCAD (Russia) which is now on the first step of clinical evaluation. BCD-085-1 study is the first-in-human clinical trial which is intended to evaluate tolerability, safety, pharmacokinetics and immunogenicity of BCD-085 when used as a single step-by-step escalating subcutaneous dose in healthy male volunteers. During this study it is expected to determine diapason of safety doses of BCD-085 (incl. MTD) which thereafter can be evaluated in phase 2 studies.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort no.1 | Experimental | This cohort includes just one subject who will receive the maximum safe starting dose of BCD-085 (0.05 mg/kg) subcutaneously. If the dose limitating toxicity occurs within the first seven days after injection the study will be stopped. If there is no DLT within mentioned above period then Cohort no.2 is included. |
|
| Cohort no.2 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 3 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 3. |
|
| Cohort no.3 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 4 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 4. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| humanized monoclonal antibody against human IL-17 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration of BCD-085-time Curve From Zero (0) Hours to 1344 Hours After the Single Subcutaneous Injection of BCD-085 | The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 h (5 min before the injection) and at 0.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours,168 hours, 336 hours, 504 hours, 672 hours, 840 hours, 1008 hours, 1176 hours, and 1344 hours following the drug administration. | 56 days |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Concentration of BCD-085 After Single Subcutaneous Injection | To assess the maximum observed concentration (Cmax) following single SC administer regardless of the cohort | 56 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time of Maximum Concentration of BCD-085 After Single Subcutaneous Injection | To assess the Tmax following single SC administer regardless of the cohort | 56 days |
| Half-life of BCD-085 After Single Subcutaneous Injection |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Roman Ivanov, PhD | JCS BIOCAD | Study Chair |
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort no.1 | This cohort includes just one subject who will receive the maximum safe starting dose of BCD-085 (0.05 mg/kg) subcutaneously. If the dose limitating toxicity occurs within the first seven days after injection the study will be stopped. If there is no DLT within mentioned above period then Cohort no.2 is included. humanized monoclonal antibody against human IL-17 |
| FG001 | Cohort no.2 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 3 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 3. humanized monoclonal antibody against human IL-17 |
| FG002 | Cohort no.3 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 4 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 4. humanized monoclonal antibody against human IL-17 |
| FG003 | Cohort no.4 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 5 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 5. humanized monoclonal antibody against human IL-17 |
| FG004 | Cohort no.5 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 6 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 6. humanized monoclonal antibody against human IL-17 |
| FG005 | Cohort no.6 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 7 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 7. humanized monoclonal antibody against human IL-17 |
| FG006 | Cohort no.7 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 8 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 8. humanized monoclonal antibody against human IL-17 |
| FG007 | Cohort no.8 | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. humanized monoclonal antibody against human IL-17 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort no.1 | This cohort includes just one subject who received the maximum safe starting dose of BCD-085 (0.05 mg/kg) subcutaneously. |
| BG001 | Cohort no.2 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Plasma Concentration of BCD-085-time Curve From Zero (0) Hours to 1344 Hours After the Single Subcutaneous Injection of BCD-085 | The blood sampling for the pharmacokinetic evaluations was performed at the following time points: 0 h (5 min before the injection) and at 0.5 hours, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours,168 hours, 336 hours, 504 hours, 672 hours, 840 hours, 1008 hours, 1176 hours, and 1344 hours following the drug administration. | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Median | Inter-Quartile Range | (ng/ml)*hour | 56 days |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort no.1 | This cohort includes just one subject who received the maximum safe starting dose of BCD-085 (0.05 mg/kg) subcutaneously. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Traumatic brain injury | Injury, poisoning and procedural complications | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated ALT | Hepatobiliary disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biryulin Andrey | BIOCAD | +7812380 49 33 | 925 | biryulin@biocad.ru |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Cohort no.4 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 5 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 5. |
|
| Cohort no.5 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 6 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 6. |
|
| Cohort no.6 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 7 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 7. |
|
| Cohort no.7 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If 0 of the 3 subjects are observed to have DLT, the dose level is escalated one step for the next cohort no. 8 of 3 subjects, and the process continues as above. If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. If none of these additional 3 patients show DLT, the dose level is escalated for the next Cohort no. 8. |
|
| Cohort no.8 | Experimental | This cohort includes 3 subjects who will receive the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. If at least 2 subjects are observed to have DLT, this dose level is defined as the MTD (unless only 3 patients have been treated at that level, in which case it is the tentative MTD). If exactly 1 of the 3 subjects treated show DLT, 3 additional subjects are treated at the current dose level. |
|
|
| 56 days |
| Constant of Elimination of BCD-085 After Single Subcutaneous Injection | 56 days |
| Clearance of BCD-085 After Single Subcutaneous Injection | 56 days |
| Mean Pain Score by VAS Assessment During Injection of BCD-085 | The study subject assesses how painful was the injection. Assessment is performed by filling out a special 10-score visual analogue scale (VAS) immediately after the injection is done. The 0 score refers to no pain, the score 10 refers to the highest, almost unbearable pain. The pain was assessed after a single injection. | day 1 |
| Total Frequency of AE/SAE | 56 days |
| Frequency of Local Reactions | 56 days |
| Frequency of Grade 3-4 AEs | 56 days |
| Frequency of Early Discontinuation Due to AE | 56 days |
| Frequency of Binding Antibodies to BCD-85 Formation | day 56 |
| BG002 | Cohort no.3 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. |
| BG003 | Cohort no.4 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. |
| BG004 | Cohort no.5 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. |
| BG005 | Cohort no.6 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. |
| BG006 | Cohort no.7 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. |
| BG007 | Cohort no.8 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. |
| BG008 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Cohort 3 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. |
| OG002 | Cohort 4 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. |
| OG003 | Cohort 5 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. |
| OG004 | Cohort 6 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. |
| OG005 | Cohort 7 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. |
| OG006 | Cohort 8 | This cohort includes subjects who received the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. |
|
|
| Secondary | Maximum Concentration of BCD-085 After Single Subcutaneous Injection | To assess the maximum observed concentration (Cmax) following single SC administer regardless of the cohort | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Mean | Standard Deviation | ng/mL | 56 days |
|
|
|
| Other Pre-specified | Time of Maximum Concentration of BCD-085 After Single Subcutaneous Injection | To assess the Tmax following single SC administer regardless of the cohort | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Median | Full Range | hours | 56 days |
|
|
|
| Other Pre-specified | Half-life of BCD-085 After Single Subcutaneous Injection | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Median | Full Range | hours | 56 days |
|
|
|
| Other Pre-specified | Constant of Elimination of BCD-085 After Single Subcutaneous Injection | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Mean | Standard Deviation | hours^-1 | 56 days |
|
|
|
| Other Pre-specified | Clearance of BCD-085 After Single Subcutaneous Injection | The analysis population includes all subjects for whom not more than 2 blood samples for BCD-085 assay were missing or unevaluable, and for whom no violations of blood sampling schedule were reported. Results of PK parameters consider in Cohort 1 and 2 together since the same dose were injected. | Posted | Mean | Standard Deviation | mL/h | 56 days |
|
|
|
| Other Pre-specified | Mean Pain Score by VAS Assessment During Injection of BCD-085 | The study subject assesses how painful was the injection. Assessment is performed by filling out a special 10-score visual analogue scale (VAS) immediately after the injection is done. The 0 score refers to no pain, the score 10 refers to the highest, almost unbearable pain. The pain was assessed after a single injection. | The safety analysis will include all subjects received BCD-085. | Posted | Mean | Standard Deviation | score on a scale | day 1 |
|
|
|
| Other Pre-specified | Total Frequency of AE/SAE | The analysis population includes subjects who received any dose of BCD-085 subcutaneously. | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Other Pre-specified | Frequency of Local Reactions | Safety population included all subjects who received at least one injection of the study drug | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Other Pre-specified | Frequency of Grade 3-4 AEs | The safety population included all subjects who received at least one injection of the study drug | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Other Pre-specified | Frequency of Early Discontinuation Due to AE | The safety population included all subjects who received at least one injection of the study drug | Posted | Count of Participants | Participants | 56 days |
|
|
|
| Other Pre-specified | Frequency of Binding Antibodies to BCD-85 Formation | Immunogenicity was evaluated in all volunteers who received the drug administration, and who had both samples, available for analysis. Volunteer from Cohort 3 had early withdrawal, so he did not have a second sample for the study. Thus, the total number of volunteers for immunogenicity assessment was 21. | Posted | Count of Participants | Participants | day 56 |
|
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Cohort no.2 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg. | 0 | 3 | 0 | 3 |
| EG002 | Cohort no.3 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.25 mg/kg. | 1 | 3 | 1 | 3 |
| EG003 | Cohort no.4 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 0.825 mg/kg. | 0 | 3 | 0 | 3 |
| EG004 | Cohort no.5 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.25 mg/kg. | 0 | 3 | 2 | 3 |
| EG005 | Cohort no.6 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 1.75 mg/kg. | 0 | 3 | 1 | 3 |
| EG006 | Cohort no.7 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 2.25 mg/kg. | 0 | 3 | 0 | 3 |
| EG007 | Cohort no.8 | This cohort includes 3 subjects who received the single subcutaneous injection of BCD-085 at a dose of 3.0 mg/kg. | 0 | 3 | 0 | 3 |
| Elevated AST | Hepatobiliary disorders | Systematic Assessment |
|
| Traumatic brain injury | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
Not provided
Not provided
| Total frequency of SAEs |
|