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Trial record 114 of 347 for:    hepatitis b | Open Studies

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02956850
First received: November 3, 2016
Last updated: NA
Last verified: November 2016
History: No changes posted
  Purpose
This sponsor-open, investigator- and participant-blinded, multi-center study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020531 in healthy participants and in participants with chronic hepatitis B. Part I will be conducted in two portions: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) which will include only healthy volunteers. Part II will commence after completion of the MAD portion of Part I and will include only Chronic Hepatitis B (CHB) participants.

Condition Intervention Phase
Hepatitis B, Chronic
Other: Placebo
Drug: RO7020531
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Part I: Percentage of Participants With Adverse Events [ Time Frame: From randomization up to Day 41 ] [ Designated as safety issue: No ]
  • Part II: Percentage of Participants With Adverse Events [ Time Frame: From randomization up to Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part I: Maximum Observed Plasma Concentration (Cmax) of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: SAD:Predose(0-2 hours [hrs] before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24,36,48 hrs postdose. MAD:Predose(0-2 hrs before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24 hrs postdose on Day 1,13; Predose(0-2 hrs before dose),2,6,24 hrs postdose on Day 3,5,7,9,11 ] [ Designated as safety issue: No ]
  • Part II: Percentage of B-Cells [ Time Frame: Predose (0-2 hrs before dose) on Day 21; 24 hrs postdose on Day 41; Week 9 and Week 12 ] [ Designated as safety issue: No ]
  • Part II: Percentage of NK Cells [ Time Frame: Predose (0-2 hrs before dose) on Day 21; 24 hrs postdose on Day 41; Week 9 and Week 12 ] [ Designated as safety issue: No ]
  • Part II: Percentage of Myeloid Cells [ Time Frame: Predose (0-2 hrs before dose) on Day 21; 24 hrs postdose on Day 41; Week 9 and Week 12 ] [ Designated as safety issue: No ]
  • Part II: Percentage of Plasmacytoid Dendritic Cells (pDCs) [ Time Frame: Predose (0-2 hrs before dose) on Day 21; 24 hrs postdose on Day 41; Week 9 and Week 12 ] [ Designated as safety issue: No ]
  • Part II: Cmax of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: Predose (0-2 hrs before dose), 0.25, 1, 2, 4, 6, 8, 24 hrs postdose on Days 1, 41; Predose (0-2 hrs before dose), 2-4 hrs postdose on Days 3, 7, 21 ] [ Designated as safety issue: No ]
  • Part I: Time to Reach Cmax (Tmax) of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: SAD: Predose(0-2 hrs before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24,36,48 hrs postdose. MAD: Predose (0-2 hrs before dose), 0.25,0.5,1,1.5,2,3,4,6,8,12,18,24 hrs postdose on Days 1,13; Predose (0-2 hrs before dose), 2,6,24 hrs postdose on Days 3,5,7,9,11 ] [ Designated as safety issue: No ]
  • Part II: Tmax of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: Predose (0-2 hrs before dose), 0.25, 1, 2, 4, 6, 8, 24 hrs postdose on Days 1, 41; Predose (0-2 hrs before dose), 2-4 hrs postdose on Days 3, 7, 21 ] [ Designated as safety issue: No ]
  • Part I: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: SAD: Predose(0-2 hrs before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24,36,48 hrs postdose. MAD: Predose (0-2 hrs before dose), 0.25,0.5,1,1.5,2,3,4,6,8,12,18,24 hrs postdose on Days 1,13; Predose (0-2 hrs before dose), 2,6,24 hrs postdose on Days 3,5,7,9,11 ] [ Designated as safety issue: No ]
  • Part II: AUCinf of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: Predose (0-2 hrs before dose), 0.25, 1, 2, 4, 6, 8, 24 hrs postdose on Days 1, 41; Predose (0-2 hrs before dose), 2-4 hrs postdose on Days 3, 7, 21 ] [ Designated as safety issue: No ]
  • Part I: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: SAD: Predose(0-2 hrs before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24,36,48 hrs postdose. MAD: Predose (0-2 hrs before dose), 0.25,0.5,1,1.5,2,3,4,6,8,12,18,24 hrs postdose on Days 1,13; Predose (0-2 hrs before dose), 2,6,24 hrs postdose on Days 3,5,7,9,11 ] [ Designated as safety issue: No ]
  • Part II: AUClast of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: Predose (0-2 hrs before dose), 0.25, 1, 2, 4, 6, 8, 24 hrs postdose on Days 1, 41; Predose (0-2 hrs before dose), 2-4 hrs postdose on Days 3, 7, 21 ] [ Designated as safety issue: No ]
  • Part I: Half-Life (t1/2) of RO7020531; and its Metabolites Including RO7011785, RO7018822 and RO7033805 [ Time Frame: SAD: Predose(0-2 hrs before dose),0.25,0.5,1,1.5,2,3,4,6,8,12,18,24,36,48 hrs postdose. MAD: Predose (0-2 hrs before dose), 0.25,0.5,1,1.5,2,3,4,6,8,12,18,24 hrs postdose on Days 1,13; Predose (0-2 hrs before dose), 2,6,24 hrs postdose on Days 3,5,7,9,11 ] [ Designated as safety issue: No ]
  • Part II: t1/2 of RO7020531; and its Metabolites including RO7011785, RO7018822 and RO7033805 [ Time Frame: Predose (0-2 hrs before dose), 0.25, 1, 2, 4, 6, 8, 24 hrs postdose on Days 1, 41; Predose (0-2 hrs before dose), 2-4 hrs postdose on Days 3, 7, 21 ] [ Designated as safety issue: No ]
  • Part I: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine [ Time Frame: 0 to 24 hrs post-dose on Day 1 ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Neopterin Levels [ Time Frame: SAD: Days 1, 2, 3, 5, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Interferon (INF)-alpha Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Interferon Gamma-Inducible Protein 10 (IP-10) Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Tumor Necrosis Factor (TNF)-alpha Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma IL-6 Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma IL-10 Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma IL-12p40 Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Interferon-Stimulated Gene (ISG) 15 messenger Ribonucleic Acid (mRNA) Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Oligoadenylate Synthetase (OAS)-1 mRNA Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Myxovirus Resistance 1 gene (MX1) mRNA Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part I and II: Pharmacodynamics: Plasma Toll-Like Receptor (TLR) 7 mRNA Levels [ Time Frame: SAD: Days 1, 8. MAD: Days 1, 3, 5, 7, 13, 20. Part II: Days 1, 3, 7, 21, 41 (detailed timeframe is provided in outcome measure description) ] [ Designated as safety issue: No ]
  • Part II: Percentage of T-Cells [ Time Frame: Predose (0-2 hrs before dose) on Day 21; 24 hrs postdose on Day 41; Week 9 and Week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: December 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I: MAD in Healthy Volunteers
Healthy volunteers will receive RO7020531 (dose as selected based on safety, PK and PD data of SAD cohorts) or matching placebo orally every other day (QOD) from Day 1 through to Day 13.
Other: Placebo
Placebo matched to RO7020531 will be administered as per schedule specified in the respective arm.
Drug: RO7020531
RO7020531 will be administered as per schedule specified in the respective arm.
Experimental: Part I: SAD in Healthy Volunteers
Healthy volunteers will receive single dose of RO7020531 or matching placebo orally on Day 1 of each cohort. A planned dose-escalation sequence for SAD is 3 mg, 10 mg, 30 mg, 90 mg, 180 mg.
Other: Placebo
Placebo matched to RO7020531 will be administered as per schedule specified in the respective arm.
Drug: RO7020531
RO7020531 will be administered as per schedule specified in the respective arm.
Experimental: Part II: CHB Participants
CHB participants will receive RO7020531 (dose as selected based on safety, PK and PD data of MAD cohorts) or matching placebo orally QOD from Day 1 through to Day 41.
Other: Placebo
Placebo matched to RO7020531 will be administered as per schedule specified in the respective arm.
Drug: RO7020531
RO7020531 will be administered as per schedule specified in the respective arm.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Part 1: SAD and MAD in Healthy Volunteers

  • A Body Mass Index (BMI) between 18 to 30 kilograms per square meter (kg/m^2), inclusive
  • Non-smokers, or use of less than (<) 10 cigarettes (or equivalent nicotine-containing product) per day
  • 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 Part 2: CHB Participants
  • A BMI between 18 to 32 kg/m^2, inclusive
  • CHB infection (positive test for Hepatitis B surface antigen [HBsAg] for more than 6 months prior to randomization)
  • HBsAg detectable at screening
  • Hepatitis B Virus (HBV) deoxyribonucleic acid (DNA) <90 international units per milliliter (IU/mL) for at least 6 months prior to randomization; HBV DNA <90 IU/mL at screening by Roche Cobas assay
  • Negative 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
  • Liver biopsy, fibroscan® or equivalent elastography test obtained within 6 months prior to randomization demonstrating liver disease consistent with chronic HBV infection with absence of cirrhosis and absence of extensive bridging fibrosis (cirrhosis or extensive bridging fibrosis are defined as greater than or equal to (>/=) Metavir 3, recommended cut-off for fibroscan 8.5 kilopascals [kPa])
  • On treatment with tenofovir, entecavir, adefovir, or telbivudine, either as single agents or in combination, for at least 6 months

Exclusion Criteria:

Part 1: SAD and MAD in Healthy Volunteers

  • History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant thyroid disease, psychiatric disease, acute infection (e.g., influenza), gastrointestinal (GI) disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage)
  • Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
  • Positive Hepatitis A virus antibody (HAV Ab IgM), HBsAg, Hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at screening
  • History of clinically significant thyroid disease; also, participants with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at screening
  • Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody Part 2: CHB Participants
  • History of liver cirrhosis
  • History or other evidence of bleeding from esophageal varices
  • Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices)
  • History or other evidence of a medical condition associated with chronic liver disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steato-hepatitis, etc.)
  • Documented history or other evidence of metabolic liver disease within one year of randomization
  • Positive test for Hepatitis A virus (IgM anti-HAV), HCV, Hepatitis D or HIV
  • History of or suspicion of hepatocellular carcinoma or alpha fetoprotein >/=13 nanograms per milliliter (ng/mL) at screening
  • History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant thyroid disease, psychiatric disease, acute infection (e.g., influenza), GI disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage)
  • History of organ transplantation
  • Clinically significant thyroid disease; also, participants with clinically significant elevated TSH concentrations at screening
  • Positive results for AMA, ASMA or thyroid peroxidase antibody
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02956850

Contacts
Contact: Reference Study ID Number: NP39305 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02956850     History of Changes
Other Study ID Numbers: NP39305 
Study First Received: November 3, 2016
Last Updated: November 3, 2016
Health Authority: New Zealand: New Zealand Medicines and Medical Devices Safety Authority

Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Hepatitis, Chronic

ClinicalTrials.gov processed this record on December 07, 2016