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To evaluate the safety and tolerability of single and multiple ascending doses of oral RO7020531 in Chinese healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Ascending Dose (SAD): Placebo | Experimental | In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort. |
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| SAD: Cohort 1 | Experimental | Eight participants will be administered 40mg RO7020531 orally on Day 1. |
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| SAD: Cohort 2 | Experimental | Eight participants will be administered 100mg RO7020531 orally on Day 1. |
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| SAD: Cohort 3 | Experimental | Eight participants will be administered 140mg RO7020531 orally on Day 1. |
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| SAD: Cohort 4 | Experimental | Eight participants will be administered 170mg RO7020531 orally on Day 1. |
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| Multiple Ascending Dose (MAD): Placebo | Experimental | In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO7020531 | Drug | 4 SAD Cohorts with individual dosages of 40, 100, 140 and 170 mg hard capsules and 3 MAD Cohorts with dosages of 100 and 150mg hard capsules, will be administered orally as per the dosing schedules described above. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, any deterioration in a laboratory value or other clinical test or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment. | Screening up until 28 days after the last dose of study drug (up to 1 year). |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Cmax will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Prince of Wales Hospital | Shatin, New Territories | Hong Kong |
A total of 70 Healthy Male and Female Chinese Participants were enrolled.
The study was conducted at 1 Center in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Single Ascending Dose (SAD): Placebo | In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort. |
| FG001 | SAD: Cohort 1 | Eight participants will be administered 40mg RO7020531 orally on Day 1. |
| FG002 | SAD: Cohort 2 | Eight participants will be administered 100mg RO7020531 orally on Day 1. |
| FG003 | SAD: Cohort 3 | Eight participants will be administered 140mg RO7020531 orally on Day 1. |
| FG004 | SAD: Cohort 4 | Eight participants will be administered 170mg RO7020531 orally on Day 1. |
| FG005 | Multiple Ascending Dose (MAD): Placebo | In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort. |
| FG006 | MAD: Cohort 1 | Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
| FG007 | MAD: Cohorts 2 and 3 | Sixteen participants will be administered 150mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Single Ascending Dose (SAD): Placebo | In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort. |
| BG001 | SAD: Cohort 1 | Eight participants will be administered 40mg RO7020531 orally on Day 1. |
| Units | Counts |
|---|---|
| Participants |
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| 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 | Percentage of Participants With Adverse Events (AEs) | An Adverse Event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease, recurrence of an intermittent medical condition, any deterioration in a laboratory value or other clinical test or adverse events that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment. | The Safety Population was defined as all Healthy Volunteers who have received at least one dose of the study medication, whether prematurely withdrawn from the study or not. | Posted | Number | Percentage of Participants | Screening up until 28 days after the last dose of study drug (up to 1 year). |
|
Screening up until 28 days after the last dose of study drug (up to 1 year).
The Safety Population was defined as all Healthy Volunteers who have received at least one dose of the study medication, whether prematurely withdrawn from the study or not. AEs that were entered into the database at the time of the database lock were included in the AE analysis.
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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 | Single Ascending Dose (SAD): Placebo | In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800 821-8590 | genentech@druginfo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 18, 2017 | May 5, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C000728203 | RO7020531 |
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|
| MAD: Cohort 1 | Experimental | Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
|
| MAD: Cohorts 2 and 3 | Experimental | Sixteen participants will be administered 150mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
|
| Placebo | Drug | Placebo hard capsules will be administered orally as per the dosing schedules described above. |
|
| SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
| Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for AUClast will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
| Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for AUCinf will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). Due to insufficient plasma concentration data for RO7020531 and RO7033805, AUCinf for these 2 compounds could not be estimated. | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
| Time to Maximum Observed Plasma Concentration (Tmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Median and Full Range) for Tmax will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
| Half-Life (t1/2) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for t1/2 will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). Due to insufficient plasma concentration data for RO7020531 and RO7033805, t1/2 for these 2 compounds could not be estimated. | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
| Total Amount Excreted as RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Total Amount Excreted, will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
| Fraction Excreted as RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Fraction Excreted (Molecular Weight corrected) will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
| Renal Clearance of RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Renal Clearance will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). Due to insufficient urine concentration data for RO7020531 and RO7033805, Renal Clearance for these 2 compounds could not be estimated. | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
| Mean Concentrations of Protein and Metabolite Markers of Humoral Response | Protein and metabolite markers of humoral response include interferon (IFN)-alfa, IP-10, Tumor Necrosis Factor (TNF)-alfa, interleukin (IL)-6, IL-10, IL-12p40 and Neopterin. Summary descriptive statistics will be presented for the induction of cytokines, chemokines and neopterin and of interferon-response genes separately by treatment arm. Only mean concentrations were collected for IFN-alfa and hence why this data is only presented below. | SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
| Mean Fold Changes of Protein and Metabolite Markers of Humoral Response | Protein and metabolite markers of humoral response include interferon (IFN)-alfa, IP-10, Tumor Necrosis Factor (TNF)-alfa, interleukin (IL)-6, IL-10, IL-12p40 and Neopterin. Summary descriptive statistics will be presented for the induction of cytokines, chemokines and neopterin and of interferon-response genes separately by treatment arm. Mean fold change data is presented below. | SAD: Day -1, Pre-dose, 2, 6, 12, 24, 48 (only Neopterin), 96h (only Neopterin), Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
| Mean Fold Changes of Markers of Transcriptional Responses | Markers of transcriptional responses includes ISG15, OAS-1, MX1 and Toll-Like Receptor (TLR)7. Summary descriptive statistics will be presented for these markers separately by treatment arm. | SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2 and Day 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
| BG002 | SAD: Cohort 2 | Eight participants will be administered 100mg RO7020531 orally on Day 1. |
| BG003 | SAD: Cohort 3 | Eight participants will be administered 140mg RO7020531 orally on Day 1. |
| BG004 | SAD: Cohort 4 | Eight participants will be administered 170mg RO7020531 orally on Day 1. |
| BG005 | Multiple Ascending Dose (MAD): Placebo | In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort. |
| BG006 | MAD: Cohort 1 | Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
| BG007 | MAD: Cohorts 2 and 3 | Sixteen participants will be administered 150mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
| BG008 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
|
In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort. |
| OG001 | SAD: Cohort 1 | Eight participants will be administered 40mg RO7020531 orally on Day 1. |
| OG002 | SAD: Cohort 2 | Eight participants will be administered 100mg RO7020531 orally on Day 1. |
| OG003 | SAD: Cohort 3 | Eight participants will be administered 140mg RO7020531 orally on Day 1. |
| OG004 | SAD: Cohort 4 | Eight participants will be administered 170mg RO7020531 orally on Day 1. |
| OG005 | Multiple Ascending Dose (MAD): Placebo | In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort. |
| OG006 | MAD: Cohort 1 | Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
| OG007 | MAD: Cohorts 2 and 3 | Sixteen participants will be administered 150mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. |
|
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| Secondary | Maximum Observed Plasma Concentration (Cmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Cmax will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | ng/ml | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
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| Secondary | Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for AUClast will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | hr*ng/ml | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
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| Secondary | Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for AUCinf will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). Due to insufficient plasma concentration data for RO7020531 and RO7033805, AUCinf for these 2 compounds could not be estimated. | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | hr*ng/ml | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
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| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Median and Full Range) for Tmax will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Median | Full Range | hr | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
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| Secondary | Half-Life (t1/2) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805) | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for t1/2 will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and SAD Cohorts (1-4) (on Day 13). Due to insufficient plasma concentration data for RO7020531 and RO7033805, t1/2 for these 2 compounds could not be estimated. | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | hr | SAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 hours (h) Post-dose Days 1, 2; MAD: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24h Post-dose Days 1, 2 and Days 13, 14; Pre-dose, 2, 6, 24hr Post-dose Days 3, 5, 7, 9 and 11. |
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| Secondary | Total Amount Excreted as RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Total Amount Excreted, will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | mg | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
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| Secondary | Fraction Excreted as RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Fraction Excreted (Molecular Weight corrected) will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | Percentage | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
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| Secondary | Renal Clearance of RO7020531, RO7011785, RO7018822 and RO7033805 | Non-compartmental analysis using WinNonlin software was used to calculate PK parameters where appropriate. Summary descriptive statistics (Arithmetic Mean and Standard Deviation) for Renal Clearance will be presented by treatment arm. Where appropriate, data maybe pooled and analyzed. Please note that this Outcome Measure was not measured for the Placebo Cohorts and MAD Cohorts (1-4). Due to insufficient urine concentration data for RO7020531 and RO7033805, Renal Clearance for these 2 compounds could not be estimated. | The PK analysis population included all healthy volunteers randomised and adherent to the protocol. Participants were excluded if they significantly violated the inclusion/exclusion criteria, deviated significantly from the protocol or if data were unavailable or incomplete. Data presented is only for participants included in the actual analysis. | Posted | Mean | Standard Deviation | CLr (mL/min) | SAD: Pre-dose, 0-4, 4-8, 8-12, 12-24h Day 1 |
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| Secondary | Mean Concentrations of Protein and Metabolite Markers of Humoral Response | Protein and metabolite markers of humoral response include interferon (IFN)-alfa, IP-10, Tumor Necrosis Factor (TNF)-alfa, interleukin (IL)-6, IL-10, IL-12p40 and Neopterin. Summary descriptive statistics will be presented for the induction of cytokines, chemokines and neopterin and of interferon-response genes separately by treatment arm. Only mean concentrations were collected for IFN-alfa and hence why this data is only presented below. | The Pharmacodynamic (PD) analysis population was defined as all participants who were randomized, received at least one dose of study medication (RO7020531 or placebo), and have PD data available. | Posted | Geometric Mean | Standard Deviation | ng/L | SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
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| Secondary | Mean Fold Changes of Protein and Metabolite Markers of Humoral Response | Protein and metabolite markers of humoral response include interferon (IFN)-alfa, IP-10, Tumor Necrosis Factor (TNF)-alfa, interleukin (IL)-6, IL-10, IL-12p40 and Neopterin. Summary descriptive statistics will be presented for the induction of cytokines, chemokines and neopterin and of interferon-response genes separately by treatment arm. Mean fold change data is presented below. | The Pharmacodynamic (PD) analysis population was defined as all participants who were randomized, received at least one dose of study medication (RO7020531 or placebo), and have PD data available. | Posted | Geometric Mean | Full Range | Fold Change | SAD: Day -1, Pre-dose, 2, 6, 12, 24, 48 (only Neopterin), 96h (only Neopterin), Post-dose Day 1 to Day 2, 3, 5, 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
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| Secondary | Mean Fold Changes of Markers of Transcriptional Responses | Markers of transcriptional responses includes ISG15, OAS-1, MX1 and Toll-Like Receptor (TLR)7. Summary descriptive statistics will be presented for these markers separately by treatment arm. | The PD analysis population was defined as all participants who were randomized, received at least one dose of study medication (RO7020531 or placebo), and have PD data available. | Posted | Geometric Mean | Full Range | Fold Change | SAD: Day -1, Pre-dose, 2, 6, 12, 24h Post-dose Day 1 to Day 2 and Day 8; MAD: Day -1, Pre-dose 2, 6, 12, 24h Post-dose Day 1 to Day 2, Pre-dose, 2, 6, 24h Post-dose Days 3, 5, 7, 13 and 20 |
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|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | SAD: Cohort 1 | Eight participants will be administered 40mg RO7020531 orally on Day 1. | 0 | 8 | 0 | 8 | 3 | 8 |
| EG002 | SAD: Cohort 2 | Eight participants will be administered 100mg RO7020531 orally on Day 1. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG003 | SAD: Cohort 3 | Eight participants will be administered 140mg RO7020531 orally on Day 1. | 0 | 8 | 0 | 8 | 4 | 8 |
| EG004 | SAD: Cohort 4 | Eight participants will be administered 170mg RO7020531 orally on Day 1. | 0 | 8 | 1 | 8 | 7 | 8 |
| EG005 | Multiple Ascending Dose (MAD): Placebo | In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG006 | MAD: Cohort 1 | Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. | 0 | 8 | 0 | 8 | 8 | 8 |
| EG007 | MAD: Cohorts 2 and 3 | Sixteen participants will be administered 150mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days. | 0 | 16 | 0 | 16 | 15 | 16 |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
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| Sinus tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Gingival swelling | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site bruise | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site erythema | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site hypoaesthesia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site pruritus | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Catheter site swelling | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | MedDRA 21.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
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| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 21.1 | Systematic Assessment |
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| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
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| Peripheral coldness | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
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The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
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| Day 13 (RO7020531) |
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| Day 1 (RO7011785) |
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| Day 13 (RO7011785) |
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| Day 1 (RO7018822) |
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| Day 13 (RO7018822) |
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| Day 1 (RO7033805) |
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| Day 13 (RO7033805) |
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| Day 13 (RO7020531) |
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| Day 1 (RO7011785) |
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| Day 13 (RO7011785) |
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| Day 1 (RO7018822) |
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| Day 13 (RO7018822) |
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| Day 1 (RO7033805) |
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| Day 13 (RO7033805) |
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| Day 13 (RO7020531) |
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| Day 1 (RO7011785) |
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| Day 13 (RO7011785) |
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| Day 1 (RO7018822) |
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| Day 13 (RO7018822) |
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| Day 1 (RO7033805) |
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| Day 13 (RO7033805) |
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| Day 13 (RO7020531) |
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| Day 1 (RO7011785) |
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| Day 13 (RO7011785) |
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| Day 1 (RO7018822) |
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| Day 13 (RO7018822) |
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| Day 1 (RO7033805) |
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| Day 13 (RO7033805) |
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| Day 13 (RO7020531) |
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| Day 1 (RO7011785) |
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| Day 13 (RO7011785) |
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| Day 1 (RO7018822) |
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| Day 13 (RO7018822) |
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| Day 1 (RO7033805) |
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| Day 13 (RO7033805) |
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| RO7011785 |
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| RO7018822 |
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| RO7033805 |
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| RO7011785 |
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| RO7018822 |
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| RO7033805 |
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| RO7011785 |
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| RO7018822 |
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| RO7033805 |
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| Neopterin |
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| Tumor Necrosis Factor (TNF)-alfa |
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| IL-6 |
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| IL-10 |
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| IL-12p40 |
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| OAS-1 mRNA |
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| MX1 mRNA |
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| TLR7 mRNA |
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