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The purpose of this study was to determine if BVS857 is safe, tolerable and increases thigh muscle thickness in patients with spinal bulbar and muscular atrophy (SBMA).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BVS857 Part A Open label (Cohort 1) | Experimental | Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. |
|
| BVS857 Part A double blind (Cohort 2) | Experimental | Participants received single doses of 0.03 mg/kg BVS857 i.v on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) |
|
| Placebo Part A double blind (Cohort 2) | Placebo Comparator | Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. |
|
| BVS857 Part B open-label (Cohort 4) | Experimental | Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. |
|
| BVS857 Part B double blind (Cohort 5) | Experimental | Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BVS857 | Drug | BVS857 lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c.. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Safety was monitored throughout the study. | After 78 days in Part A and after 85 days in Part B. |
| Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Safety was monitored throughout the study. | After 78 days in Part A and after 85 days in Part B. |
| Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5 | Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: [(Day 85/baseline) - 1)] x 100. A positive change from baseline indicates improvement. | Baseline, Day 85 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5 | The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Orange | California | 92868 | United States | ||
| National Institutes of Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30337273 | Derived | Grunseich C, Miller R, Swan T, Glass DJ, El Mouelhi M, Fornaro M, Petricoul O, Vostiar I, Roubenoff R, Meriggioli MN, Kokkinis A, Guber RD, Budron MS, Vissing J, Soraru G, Mozaffar T, Ludolph A, Kissel JT, Fischbeck KH; BVS857 study group. Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial. Lancet Neurol. 2018 Dec;17(12):1043-1052. doi: 10.1016/S1474-4422(18)30320-X. Epub 2018 Oct 15. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicaltrials.com | View source |
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In Part B, Cohort 3 was not enrolled. Cohort 4 participants received open-label BVS857. Cohort 5 participants were randomized to double-blind BVS857 or double-blind placebo in a ratio of 18:10.
This study was conducted in 2 parts, Part A and Part B. In Part A, Cohort 1 participants received open-label BVS857. Cohort 2 participants were randomized to double-blind BVS857 or double-blind placebo in a 2:1 ratio.
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| ID | Title | Description |
|---|---|---|
| FG000 | BVS857 Part A Open Label (Cohort 1) | Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. |
| FG001 | BVS857 Part A Double Blind (Cohort 2) | Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) |
| FG002 | Placebo Part A Double Blind (Cohort 2) | Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. |
| FG003 | BVS857 Part B Open-label (Cohort 4) | Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. |
| FG004 | BVS857 Part B Double Blind (Cohort 5) | Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. |
| FG005 | Placebo Part B Double Blind (Cohort 5) | Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BVS857 Part A Open Label (Cohort 1) | Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability | Safety was monitored throughout the study. | The safety analysis set, which included participants who received any study drug, was analyzed. | Posted | Number | Participants | After 78 days in Part A and after 85 days in Part B. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BVS857 Part A Open Label (Cohort 1) | Participants received single doses of 0.01 mg/kg BVS857 intravenously (i.v.) on day 1, 0.01 mg/kg BVS857 subcutaneously (s.c.) on day 15, 0.03 mg/kg BVS857 s.c. on day 29, 0.06 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eustachian tube dysfunction | Ear and labyrinth disorders | MedDRA (16.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-1873 |
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| ID | Term |
|---|---|
| D055534 | Bulbo-Spinal Atrophy, X-Linked |
| ID | Term |
|---|---|
| D009134 | Muscular Atrophy, Spinal |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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|
| Placebo Part B double blind (Cohort 5) | Placebo Comparator | Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. |
|
| Placebo | Drug | Placebo lyophilisate in vial; the lyophilisate was reconstituted with sterile water for injection, diluted as appropriate, and administered either i.v. or s.c.. |
|
| Baseline, Day 85 |
| Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5 | LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement. | Baseline, Day 85 |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4 | Serum samples were obtained for PK assessment. | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4 | Serum samples were obtained for PK assessment. | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4 | Serum samples were obtained for the PK assessment. | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
| Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) | Serum samples were obtained for PK assessment. | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2) | Serum samples were obtained for PK assessment. | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) | Serum samples were obtained for PK assessment. | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
| Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations | Serum samples were obtained for PK assessment. | In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. |
| Bethesda |
| Maryland |
| 20892 |
| United States |
| Novartis Investigative Site | Columbus | Ohio | 43210 | United States |
| Novartis Investigative Site | Copenhagen | 2100 | Denmark |
| Novartis Investigative Site | Ulm | 89081 | Germany |
| Novartis Investigative Site | Padova | PD | 35128 | Italy |
| Abnormal laboratory value |
|
| BVS857 Part A Double Blind (Cohort 2) |
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) |
| BG002 | Placebo Part A Double Blind (Cohort 2) | Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. |
| BG003 | BVS857 Part B Open-label (Cohort 4) | Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. |
| BG004 | BVS857 Part B Double Blind (Cohort 5) | Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. |
| BG005 | Placebo Part B Double Blind (Cohort 5) | Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex/Gender, Customized | Number | Participants |
|
Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) |
| OG002 | Placebo Part A Double Blind (Cohort 2) | Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. |
| OG003 | BVS857 Part B Open-label (Cohort 4) | Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. |
| OG004 | BVS857 Part B Double Blind (Cohort 5) | Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. |
| OG005 | Placebo Part B Double Blind (Cohort 5) | Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. |
|
|
| Primary | Number of Mild, Moderate and Severe Adverse Events as a Measure of Safety and Tolerability | Safety was monitored throughout the study. | The safety analysis set, which included participants who received any study drug, was analyzed. | Posted | Number | Participants | After 78 days in Part A and after 85 days in Part B. |
|
|
|
| Primary | Mean Percent Change From Baseline in Thigh Muscle Volume in Part B, Cohort 5 | Thigh muscle volume was assessed by magnetic resonance imaging (MRI). Change from baseline was calculated from the ratio of the post-baseline mean value to the baseline mean value: [(Day 85/baseline) - 1)] x 100. A positive change from baseline indicates improvement. | The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | Percent change | Baseline, Day 85 |
|
|
|
|
| Secondary | Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5 | The AMAT rated physical function and muscle endurance, with higher scores indicating better performance. The tool includes 7 timed functional tasks rated on a scale from 0 - 21 and 6 endurance tasks rated on a scale from 0 - 24. The range for the total score was from 0 (worst) to 45 (best). A positive change from baseline indicates improvement. | The PD set included, which included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data, was analyzed. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 85 |
|
|
|
| Secondary | Mean Change From Baseline in Total Lean Body Mass (LBM) in Part B, Cohort 5 | LBM was assessed by dual-energy X-ray (DXA) absorptiometry. A positive change from baseline indicate improvement. | The PD analysis set was considered for the analysis. However, only participants who had evaluable data at both baseline and day 85, were included in the analysis. The PD set included participants with evaluable PD data who received any study drug and had no protocol deviations with relevant impact on PD data. | Posted | Mean | Standard Deviation | kilograms | Baseline, Day 85 |
|
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
|
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|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
|
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|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | hours | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | hours | Day 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
|
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|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
|
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|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | H*ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 1 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part A, Cohort 2 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose |
|
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|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 4 | Serum samples were obtained for PK assessment. | The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed. | Posted | Mean | Standard Deviation | ng/mL | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Observed Maximum Concentration Following Drug Administration (Cmax) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | ng/mL | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 4 | Serum samples were obtained for PK assessment. | The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed. | Posted | Mean | Standard Deviation | hours | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | hours | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
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| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) in Part B, Cohort 5 | Serum samples were obtained for PK assessment. | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Day 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
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|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 4 | Serum samples were obtained for the PK assessment. | The PK analysis set, which included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data, was analyzed. | Posted | Mean | Standard Deviation | H*ng/mL | Days 1: pre-dose, 1, 4, 24, 48 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857:The Area Under the Plasma Concentration-time Curve From Zero to 48 Hours (AUC0_48h) in Part B, Cohort 5 | For each time point, only participants from the PK set with valid measurements at that time point were analyzed. The PK analysis set included participants with at least one available valid PK concentration measurement who received any study drug and experienced no protocol deviations with relevant impact on PK data. | Posted | Mean | Standard Deviation | h*ng/mL | Days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) | Serum samples were obtained for PK assessment. | This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated. | Posted | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Terminal Elimination Half-life (T1/2) | Serum samples were obtained for PK assessment. | This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated. | Posted | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
|
| Secondary | Plasma Pharmacokinetics (PK) of BVS857: The Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUCinf) | Serum samples were obtained for PK assessment. | This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated. | Posted | Part A: days 1, 15, 29, 43: pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. Day 57: pre-dose, 1, 4, 12, 24, 48, 168, 504 hours post-dose. Part B: days 1 and 36: pre-dose, 1, 4, 24, 48 hours post-dose. Day 78: pre-dose, 1, 4, 24, 48, 168 hours post-dose. |
|
|
| Secondary | Compare Dose Normalized Log-transformed AUCinf Following IV and SC Administrations | Serum samples were obtained for PK assessment. | This PK parameter was not analyzed in either Part A or Part B because there were insufficient data points after Cmax. Therefore, this parameter could not be calculated. | Posted | In Part A: days 1 and 15, pre-dose, 1, 4, 12, 24, 48, 168 hours post-dose. |
|
|
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Placebo Part A Double Blind (Cohort 2) | Participants received single doses of matching placebo i.v. on day 1 and matching placebo s.c. on days 15, 29, 43 and 57. | 0 | 2 | 2 | 2 |
| EG002 | BVS857 Part A Double Blind (Cohort 2) | Participants received single doses of 0.03 mg/kg BVS857 i.v. on day 1, 0.03 mg/kg BVS857 s.c. on day 15, 0.06 mg/kg BVS857 s.c. on day 29, 0.10 mg/kg BVS857 s.c. on day 43 and 0.10 mg/kg BVS857 s.c. on day 57. (BVS857 concentrations differed on days 43 and 57.) | 0 | 4 | 4 | 4 |
| EG003 | BVS857 Part B Open-label (Cohort 4) | Participants received 0.1 mg/kg BVS857 i.v. weekly for 12 weeks. | 0 | 2 | 1 | 2 |
| EG004 | BVS857 Part B Double Blind (Cohort 5) | Participants received 0.06 mg/kg (maximum 6 mg) BVS857 i.v. weekly for 12 weeks. | 0 | 18 | 17 | 18 |
| EG005 | Placebo Part B Double Blind (Cohort 5) | Participants received matching placebo i.v. to BVS857 weekly for 12 weeks. | 0 | 9 | 8 | 9 |
| Eyelid haematoma | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Glaucoma | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Scleral hyperaemia | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Lip disorder | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Lip oedema | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Periodontal disease | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Administration site hypersensitivity | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Catheter site extravasation | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Infusion site erythema | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Infusion site pruritus | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Injection site swelling | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Puncture site pain | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Therapeutic response unexpected | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
|
| Bone contusion | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA (16.1) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (16.1) | Systematic Assessment |
|
| Neutralising antibodies positive | Investigations | MedDRA (16.1) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (16.1) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Exostosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.1) | Systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.1) | Systematic Assessment |
|
| Carotid artery stenosis | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D016472 | Motor Neuron Disease |
| D009468 | Neuromuscular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Moderate |
|
| Severe |
|
| Title | Measurements |
|---|---|
|
| Day 43, 0.06 mg/kg BVS857 s.c. |
|
|
| Day 43, 0.10 mg/kg BVS857 s.c. (n=3) |
|
| Day 57, 0.10 mg/kg BVS857 s.c. (n=1) |
|
|
| Day 43, 0.06 mg/kg BVS857 s.c. (n=2) |
|
|
| Day 43, 0.10 mg/kg BVS857 s.c. (n=3) |
|
| Day 57, 0.10 mg/kg BVS857 s.c. (n=1) |
|
|
| Day 43, 0.06 mg/kg BVS857 s.c.(n=2) |
|
|
| Day 43, 0.10 mg/kg BVS857 s.c. (n=3) |
|
| Day 57, 0.10 mg/kg BVS857 s.c. (n=1) |
|
|
| Day 43, 0.06 mg/kg BVS857 s.c. (n=2) |
|
|
| Day 43, 0.10 mg/kg BVS857 s.c. (n=3) |
|
| Day 57, 0.10 mg/kg BVS857 s.c. (n=1) |
|
|
|
|