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Trial record 109 of 362 for:    hepatitis b | Recruiting, Not yet recruiting, Available 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 currently recruiting participants.
See Contacts and Locations
Verified May 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02956850
First received: November 3, 2016
Last updated: May 18, 2017
Last verified: May 2017
  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
Intervention Model: Parallel Assignment
Masking: Participant, 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 ]
  • Part II: Percentage of Participants With Adverse Events [ Time Frame: From randomization up to Week 12 ]

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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Part I: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine [ Time Frame: 0 to 24 hrs post-dose on Day 1 ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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 ]

Estimated Enrollment: 110
Actual Study Start Date: December 12, 2016
Estimated Study Completion Date: December 22, 2018
Estimated Primary Completion Date: December 22, 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)
Sexes Eligible for Study:   All
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-roche-genentech-trials@gene.com

Locations
Bulgaria
Tokuda Hospital Sofia; Hematology department Not yet recruiting
Sofia, Bulgaria, 1407
Hong Kong
Queen Mary Hospital Not yet recruiting
Hong Kong, Hong Kong
The Chinese University of Hong Kong Not yet recruiting
Shatin, Hong Kong, 123456
New Zealand
Auckland Clinical Studies Recruiting
Auckland, New Zealand, 1142
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: May 18, 2017

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 June 22, 2017