A Study to Assess the Safety and Tolerability of Single and Multiple Ascending Doses of Oral RO7020531 in Chinese Healthy Participants.

NCT03530917 | Completed Phase 1 Results

• 1 other identifier: YP39553
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of single and multiple ascending doses of oral RO7020531 in Chinese healthy participants.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (1)

• 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).

Secondary Outcomes (11)

• Maximum Observed Plasma Concentration (Cmax) for RO7020531, Main Active Metabolite (RO7011785) and Prodrug Metabolites (RO7018822 and RO7033805)

  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)

  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)

  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)

  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)

  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.

Study Arms (8)

Single Ascending Dose (SAD): Placebo

EXPERIMENTAL

In SAD Cohorts 1-4, there will be eight participants in total receiving placebo, two in each cohort.

Drug: Placebo

SAD: Cohort 1

EXPERIMENTAL

Eight participants will be administered 40mg RO7020531 orally on Day 1.

Drug: RO7020531

SAD: Cohort 2

EXPERIMENTAL

Eight participants will be administered 100mg RO7020531 orally on Day 1.

Drug: RO7020531

SAD: Cohort 3

EXPERIMENTAL

Eight participants will be administered 140mg RO7020531 orally on Day 1.

Drug: RO7020531

SAD: Cohort 4

EXPERIMENTAL

Eight participants will be administered 170mg RO7020531 orally on Day 1.

Drug: RO7020531

Multiple Ascending Dose (MAD): Placebo

EXPERIMENTAL

In MAD Cohorts 1-3, there will be six participants in total receiving placebo, two in each cohort.

Drug: Placebo

MAD: Cohort 1

EXPERIMENTAL

Eight participants will be administered 100mg RO7020531 orally on Day 1 and every other day (QOD) for 14 days.

Drug: RO7020531

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.

Drug: RO7020531

Interventions

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.

MAD: Cohort 1; MAD: Cohorts 2 and 3; SAD: Cohort 1; SAD: Cohort 2; SAD: Cohort 3; SAD: Cohort 4

Placebo DRUG

Placebo hard capsules will be administered orally as per the dosing schedules described above.

Multiple Ascending Dose (MAD): Placebo; Single Ascending Dose (SAD): Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Chinese healthy male and female participants. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
• A Body Mass Index (BMI) of 19 to less than 28 kg/m2 and a body weight of at least 45 kg.
• Negative anti-nuclear antibody (ANA) test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases.
• Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods.
• Men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and refrain from donating sperm.
• Negative pregnancy test on Day -1 for female participants.
• Non-smokers, or use of \< 10 cigarettes (or equivalent nicotine-containing product) per day.

You may not qualify if:

• Pregnant (positive pregnancy test) or lactating women, and male partners of women who are pregnant or lactating.
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease).
• History or symptoms of any clinically significant disease including (but not limited to), neurological, cardiovascular, endocrine, respiratory, hepatic, ocular, or renal disorder (as per Investigator's judgment).
• Personal or family history of congenital long QT syndrome or sudden cardiac death.
• Evidence of an active or suspected cancer or a history of malignancy, where in the Investigator's opinion, there is a risk of recurrence.
• History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids, IFN or PEG-IFN) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study. Eye drop-containing and infrequent inhaled corticosteroids are permissible up to 4 weeks prior to the first dose of study drug.
• History of clinically significant thyroid disease; also, subjects with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at Screening.
• Any confirmed clinically significant allergic reactions (anaphylaxis) against any drug, or multiple drug allergies (non-active hay fever is acceptable).
• Abnormal renal function.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values at Screening above ULN and judged clinically significant by the Investigator.
• Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody.
• Positive hepatitis A IgM antibody (HAV Ab IgM), hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at Screening.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

MeSH Terms

Interventions

RO7020531

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 21, 2018
• Study Start: May 15, 2018
• Primary Completion: May 15, 2019
• Study Completion: May 15, 2019
• Last Updated: July 13, 2020
• Results First Posted: July 13, 2020

Record last verified: 2020-07

Locations

HK (1)