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A Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of RO7062931in Healthy Volunteers and Subjects With Chronic Hepatitis B

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ClinicalTrials.gov Identifier: NCT03038113
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This randomized study will be conducted in two parts to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of subcutaneous administration of RO7062931. Part 1 will include only healthy participants and Part 2 will include only participants with chronic hepatitis B (CHB). Part 1 is an adaptive, single-ascending dose study with an adaptive dose-escalating schedule to determine the best dose to be evaluated in participants with CHB. Part 2 is an adaptive, parallel multiple-dose study comprised of three sub-parts which will be used to further refine the dose and dosing regimen, and to evaluate the safety and efficacy of RO7062931 when administered with standard-of-care (SoC) therapy.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: RO7062931 Drug: Placebo Drug: Immune Modulator Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: A Randomized, Sponsor-Open, Placebo-Controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of Subcutaneous Administration of RO7062931 With Single Ascending Doses in Healthy Volunteers and Multiple Doses and Modified Regimens in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
Actual Study Start Date : February 6, 2017
Estimated Primary Completion Date : May 1, 2021
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Single-Ascending Dose (SAD)
Healthy volunteers will be enrolled in up to 8 cohorts with doses starting from 0.1 mg/kg and escalating sequentially after review of safety and pharmacokinetic (PK) data.
Drug: RO7062931
Administered subcutaneously in Parts 1 and 2. Part 1 will be administered in single-ascending doses after 0.1 mg/kg starting dose. Subsequent doses of 0.3, 1, 2 and 4 mg/kg may be administered based upon tolerability. In Part 2a, participants will receive two monthly doses of either 0.4, 0.8, 1.2 times the saturation dose or placebo. In Part 2b, a dose selected from Part 2a will be administered to participants randomized into 4 cohorts QW or Q2W. In Part 2c, participants will receive RO7062831 QW on top of another therapy for up to 24 or 48 weeks.

Drug: Placebo
Part 1 cohorts: active drug vs placebo 4:1. Part 2a 4 parallel cohorts of 3 active drug doses and placebo in 1:1:1:1. Part 2b active drug vs placebo in 3:1 in 2 parallel cohorts.

Experimental: Part 2: Multiple Ascending Dose
Participants with Chronic Hepatitis B will enrolled in Part 2. In Part 2a, participants will receive two monthly injections of either 3 doses equivalent to a multiple of the saturation dose or placebo in a 1:1:1:1 ratio. In Part 2b, a dose selected from Part 2a will be administered to participants randomized into 4 cohorts where they will be dosed weekly (QW) or bi-weekly (Q2W). Each of the cohorts in Part 2b will include participants receiving active drug or placebo in a 3:1 ratio. In Part 2c, NUC-suppressed CHB participants will receive either RO7062931+NUC for up to 24 weeks, or RO7062931+NUC+an immune modulator for up to 48 weeks, at a dose determined from Part 2a and 2b. Part 2c may also enroll treatment-naive immune-active CHB participants.
Drug: RO7062931
Administered subcutaneously in Parts 1 and 2. Part 1 will be administered in single-ascending doses after 0.1 mg/kg starting dose. Subsequent doses of 0.3, 1, 2 and 4 mg/kg may be administered based upon tolerability. In Part 2a, participants will receive two monthly doses of either 0.4, 0.8, 1.2 times the saturation dose or placebo. In Part 2b, a dose selected from Part 2a will be administered to participants randomized into 4 cohorts QW or Q2W. In Part 2c, participants will receive RO7062831 QW on top of another therapy for up to 24 or 48 weeks.

Drug: Placebo
Part 1 cohorts: active drug vs placebo 4:1. Part 2a 4 parallel cohorts of 3 active drug doses and placebo in 1:1:1:1. Part 2b active drug vs placebo in 3:1 in 2 parallel cohorts.

Drug: Immune Modulator
Participants in Part 2c will receive an immune modulator subcutaneously QW for up to 48 weeks.




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events (AEs) and AEs of Special Interest [ Time Frame: Up to Day 113 ]
  2. Percentage of Participants with Laboratory Abnormalities Based on Hematology, Blood Chemistry, Coagulation, and Urinalysis Test Results [ Time Frame: Up to Day 113 ]
  3. Percentage of Participants with Electrocardiogram (ECG) Abnormalities [ Time Frame: Up to Day 113 ]
  4. Percentage of Participants with Abnormalities in Vital Signs, Including Blood Pressure, Heart Rate, and Temperature [ Time Frame: Up to Day 113 ]

Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  2. Maximum Plasma Concentration (Cmax) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  3. Maximum Plasma Concentration (Cmax) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  4. Maximum Plasma Concentration (Cmax) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  5. Time to Reach Maximum Plasma Concentration (Tmax) After Single-Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  6. Time to Reach Maximum Plasma Concentration (Tmax) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  7. Time to Reach Maximum Plasma Concentration (Tmax) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  8. Time to Reach Maximum Plasma Concentration (Tmax) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  9. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) After Single-Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  10. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  11. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  12. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  13. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  14. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  15. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  16. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  17. Terminal Elimination Rate Constant (k) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  18. Terminal Elimination Rate Constant (k) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  19. Terminal Elimination Rate Constant (k) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  20. Terminal Elimination Rate Constant (k) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  21. Terminal Elimination Half-Life (t1/2) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  22. Terminal Elimination Half-Life (t1/2) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  23. Terminal Elimination Half-Life (t1/2) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  24. Terminal Elimination Half-Life (t1/2) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  25. Total Clearance (CL) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  26. Total Clearance (CL) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  27. Total Clearance (CL) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  28. Total Clearance (CL) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  29. Volume of Distribution (Vss) After Single Ascending Doses - Part 1 [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 18 hours post dose Day 1; 24, 30, and 36 hours post dose Day 2; 48 hours post dose Day 3; 72 hours post dose Day 4; 96 hours post dose Day 5; 120 hours post dose Day 6; 168 hours post dose Day 8 ]
  30. Volume of Distribution (Vss) After Multiple Ascending Doses - Part 2a [ Time Frame: Predose, 0.5, 1,2, 4, 6, 8 hours post dose Day 1; 24 hours post dose Day 2; Day 8; Predose, 2 hrs post dose Day 15; Day 22; Predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Discontinuation; Days 36, 43, 50, 57 ]
  31. Volume of Distribution (Vss) After Multiple Ascending Doses - Part 2b, Every 2 Weeks (Q2W) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; Day 8; predose, 2 hours post dose Day 15; Day 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  32. Volume of Distribution (Vss) After Multiple Ascending Doses - Part 2b, Every Week (QW) [ Time Frame: Predose, 0.5, 1, 2, 4, 6, 8, hours post dose Day 1; 24 hours post dose Days 2; predose, 2 hours post dose Days 8, 15 22; predose, 0.5, 1, 2, 4, 6, 8 hours post dose Day 29; 24 hours post dose Day 30; Days 36, 43, 50, 57 ]
  33. Cumulative Amount Excreted Unchanged in Urine (Ae) After Single Ascending Doses - Part 1 [ Time Frame: 0-4, 4-8, 8-12 and 12-24 hrs post-dose on Days 1 and 2 ]
  34. Cumulative Amount Excreted Unchanged in Urine (Ae) After Multiple Ascending Doses - Part 2 [ Time Frame: 0-4, 4-8, 8-12 and 12-24 hrs post-dose on Days 1 and 2 ]
  35. Change from baseline of Quantitative HBsAg (qHBsAg) (log10) After Multiple Ascending Doses - Part 2a [ Time Frame: Screening, D1, D2, D8, D15, D22, D29 predose, D30, D36, D43, D50, D57 ]
  36. Change from baseline of Quantitative HBsAg (log10) After Multiple Ascending Doses - Part 2b, Q2W [ Time Frame: Part 2b Q2W: Screening, D1, D2, D8, D15 predose, D22, D29 predose, D30, D36, D43, D50, D57 ]
  37. Change from baseline of Quantitative HBsAg (log10) After Multiple Ascending Doses - Part 2b QW [ Time Frame: Part 2b QW: Screening, D1, D2, D8 predose, D15 predose, D22 predose, D29 predose, D30, D36, D43, D50, D57 ]
  38. Maximum Change from Baseline in Quantitative HBsAg Across All Time-Points After Multiple Ascending Doses - Part 2a [ Time Frame: Screening, D1, D2, D8, D15, D22, D29 predose, D30, D36, D43, D50, D57 ]
  39. Maximum Change from Baseline in Quantitative HBsAg Across All Time-Points After Multiple Ascending Doses - Part 2b, Q2W [ Time Frame: Part 2b Q2W: Screening, D1, D2, D8, D15 predose, D22, D29 predose, D30, D36, D43, D50, D57 ]
  40. Maximum Change from Baseline in Quantitative HBsAg Across All Time-Points After Multiple Ascending Doses - Part 2b QW [ Time Frame: Part 2b QW: Screening, D1, D2, D8 predose, D15 predose, D22 predose, D29 predose, D30, D36, D43, D50, D57 ]
  41. Rate of Decrease for HBsAg at Each Time-Point After Multiple Ascending Doses - Part 2a [ Time Frame: Screening, D1, D2, D8, D15, D22, D29 predose, D30, D36, D43, D50, D57 ]
  42. Rate of Decrease for HBsAg at Each Time-Point After Multiple Ascending Doses - Part 2b, Q2W [ Time Frame: Part 2b Q2W: Screening, D1, D2, D8, D15 predose, D22, D29 predose, D30, D36, D43, D50, D57 ]
  43. Rate of Decrease for HBsAg at Each Time-Point After Multiple Ascending Doses - Part 2b QW [ Time Frame: Part 2b QW: Screening, D1, D2, D8 predose, D15 predose, D22 predose, D29 predose, D30, D36, D43, D50, D57 ]
  44. Proportion of Participants with Undetectable qHBsAg - Part 2c QW for 24 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, and 25 ]
  45. Proportion of Participants with Undetectable qHBsAg - Part 2c QW for 48 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, 25, 30, 36, 42, 48, 49 ]
  46. Maximum Plasma Concentration (Cmax) After Multiple Ascending Doses - Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  47. Maximum Plasma Concentration (Cmax) After Multiple Ascending Doses - Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  48. Time to Reach Maximum Plasma Concentration (Tmax)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  49. Time to Reach Maximum Plasma Concentration (Tmax)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  50. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  51. Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUC0-inf)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  52. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  53. Area Under the Plasma Concentration-Time Curve from Time Zero until the Last Quantifiable Time-Point (AUC0-last)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  54. Terminal Elimination Rate Constant (k)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  55. Terminal Elimination Rate Constant (k)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  56. Terminal Elimination Half-Life (t1/2)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  57. Terminal Elimination Half-Life (t1/2)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  58. Total Clearance (CL)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  59. Total Clearance (CL)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  60. Volume of Distribution (Vss)- Part 2c, QW for 24 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, and 24; Day 2 of Weeks 1, 12, and 24; predose Weeks 2, 13, and 25 ]
  61. Volume of Distribution (Vss)- Part 2c, QW for 48 Weeks [ Time Frame: Predose, 0.5, 1, 2, 4, 6, and 8 hours post-dose Day 1 of Weeks 1, 12, 24, and 48; Day 2 of Weeks 1, 12, 24, and 48; predose Weeks 2, 13, and 25, and Week 49 ]
  62. Cumulative Amount Excreted Unchanged in Urine (Ae)- Part 2c, QW for 24 Weeks [ Time Frame: 0-4 and 4-8 hours post-dose on Day 1 of Weeks 1, 12, and 24 ]
  63. Cumulative Amount Excreted Unchanged in Urine (Ae)- Part 2c, QW for 48 Weeks [ Time Frame: 0-4 and 4-8 hours post-dose on Day 1 of Weeks 1, 12, 24, and 48 ]
  64. Change from baseline of Quantitative HBsAg (log10)- Part 2c, QW for 24 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, and 25 ]
  65. Change from baseline of Quantitative HBsAg (log10)- Part 2c, QW for 48 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, 25, 30, 36, 42, 48, 49 ]
  66. Maximum Change from Baseline in Quantitative HBsAg Across All Time-Points- Part 2c, QW for 24 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, and 25 ]
  67. Maximum Change from Baseline in Quantitative HBsAg Across All Time-Points- Part 2c, QW for 48 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, 25, 30, 36, 42, 48, 49 ]
  68. Rate of Decrease for HBsAg at Each Time-Point- Part 2c, QW for 24 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, and 25 ]
  69. Rate of Decrease for HBsAg at Each Time-Point- Part 2c, QW for 48 Weeks [ Time Frame: At screening and predose Day 1, and Weeks 2, 4, 8, 12, 13, 18, 24, 25, 30, 36, 42, 48, 49 ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

FOR HEALTHY VOLUNTEERS ONLY - PART 1 -

  • A Body Mass Index (BMI) between 18 to 30 kg/m2 inclusive and a body weight of at least 50 kg.
  • Women should be of non-childbearing potential. A woman is considered to be of childbearing potential if she is post-menarcheal but has not reached a post-menopausal state and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures during treatment and up to 105 days after the last dose, and agree to refrain from donating sperm.
  • Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1 and agree to remain as non-smoker during the study.

FOR CHB PARTICIPANTS ONLY - PARTS 2a and 2b:

  • A BMI between 18 to 32 kg/m2 inclusive.
  • Chronic hepatitis B (HBV) infection.
  • Positive test for HBsAg for more than 6 months prior to randomization and HBsAg titer ≥ 10^3 IU/mL at screening.
  • On entecavir, tenofovir, adefovir or telbivudine treatment for at least 6 months prior to randomization and will remain on stable treatment during the study.
  • HBV deoxyribonucleic acid (DNA) ≤ 90 IU/mL for at least the preceding 6 months.
  • Screening laboratory values (hematology, chemistry, urinalysis) obtained up to 56 days prior to first study treatment within normal ranges.
  • Liver biopsy, fibroscan® or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis
  • Women should be of non-childbearing potential. A woman is considered to be of childbearing potential if she is post-menarcheal but has not reached a post-menopausal state and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures during treatment and up to 105 days after the last dose, and agree to refrain from donating sperm.

FOR CHB PARTICIPANTS ONLY - PART 2c

  • BMI between 18 to 32 kg/m2 inclusive
  • CHB infection (HBsAg-positive for at least 6 months)
  • For NUC-suppressed CHB participants: Must have been treated with a single NUC for at least 12 months, and have been on the same NUC therapy for at least 3 months prior to screening; HBV DNA <lower limit of quantification (LLOQ) at screening and in the 6 months prior to screening (at least one measurement must be >30 days prior to screening); alanine aminotransferase (ALT) </=2x upper limit of normal (ULN) for >6 months prior to screening and confirmed at screening; total bilirubin within normal range at screening, except for patients with Gilbert's syndrome
  • For treatment-naive and immune-active participants: HBV DNA at screening >/=2x10^4 IU/mL for HBeAg positive participants, or >/=2x10^3 IU/mL for HBeAg negative participants; elevated serum ALT>2 ULN to </=5, 2 values within 6 months, at least one of which is at screening and that are at least 14 days apart; total bilirubin within normal range except for participants with Gilbert's syndrome
  • Screening laboratory values (hematology, chemistry, urinalysis) obtained up to 28 days prior to first study treatment within normal ranges
  • Liver biopsy, fibroscan, or equivalent test obtained within the last 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis
  • Women should be of non-childbearing potential
  • Men must agree to remain abstinent or use contraception, and agree to refrain from donating sperm

Exclusion Criteria:

FOR HEALTHY VOLUNTEERS ONLY - PART 1:

  • History of drug or alcohol abuse or dependence in previous 6 months.
  • Positive urine drug and alcohol screen or positive cotinine test at screening or Day -1.
  • Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2.
  • Confirmed blood pressure or resting pulse rate outside of accepted ranges.
  • Participation in an investigational drug or device study within 90 days prior to screening.
  • Donation of blood over 500 mL within three months prior to screening.
  • Any major illness within the one month, or any febrile illness within two weeks preceding the screening visit.
  • Alcohol consumption of more than 2 standard drinks per day on average.

FOR CHB PARTICIPANTS ONLY - PARTS 2a and 2b:

  • History or other evidence of bleeding from esophageal varices.
  • Decompensated liver disease.
  • History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) ≥ 13 ng/mL at Screening
  • History or other evidence of a medical condition associated with chronic liver disease other than HBV infection.
  • Documented history or other evidence of metabolic liver disease within one year of randomization or documented history of infection with hepatitis D virus.
  • Positive test for hepatitis A (IgM anti-HAV), hepatitis C, or HIV.
  • Organ transplantation.
  • Significant acute infection or any other clinically significant illness within 2 weeks of randomization.
  • Abnormal renal function.
  • Participation in an investigational drug or device study within 30 days prior to randomization.
  • Donation or loss of blood over 500 mL within 3 months prior to starting study medication.
  • Administration of any blood product within 3 months of randomization.
  • History or evidence of alcohol abuse (consumption of more than 2 standard drinks per day on average).

FOR CHB PARTICIPANTS ONLY - PART 2c

  • History or other evidence of bleeding from esophageal varices
  • Evidence of liver cirrhosis or decompensated liver disease
  • One or more of the following laboratory abnormalities at screening: Total serum bilirubin > ULN (except for participants with Gilbert's disease); international normalized ratio (INR) > 1.1 ULN; serum albumin < 3.5 g/dL; AFP >13 ng/mL; positive results for anti-mitochondrial antibodies (AMA > 1:80), anti-nuclear antibody (ANA > 1:80), anti-smooth muscle antibody (ASMA > 1:40), anti-thyroperoxidase antibodies (a-TPO), anti-thyroglobulin, or anti-platelet antibodies; thyroid stimulating hormone (TSH) outside of normal range; platelet count <100,000 cells/mm^3; hemoglobin <12 g/dL (females) or <13 g/dL (males); white blood cell count <2500 cells/mm^3; and neutrophil count <1500 cells/mm^3
  • History or other evidence of a medical condition associated with chronic liver disease other than HBV infection
  • History of thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests
  • Documented history or other evidence of metabolic liver disease within one year of randomization
  • Positive test for hepatitis A, hepatitis C, or HIV
  • History of organ transplantation
  • Participation in an investigational drug or device study within 30 days prior to screening or previous treatment with an investigational agent for HBV within 6 months prior to screening
  • Significant acute infection or any other clinically significant illness within 2 weeks of randomization
  • Abnormal renal function, including serum creatinine > ULN or calculated creatinine clearance < 70 mL/min
  • Donation or loss of blood over 500 mL within 3 months prior to randomization
  • Administration of any blood product within 3 months prior to randomization
  • History of alcohol abuse and/or drug abuse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03038113


Contacts
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Contact: eference Study ID Number: BP39405 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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Australia, Victoria
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Linear Clinical Research Limited Recruiting
Nedlands, Western Australia, Australia, 6009
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Prince of Wales Hospital Recruiting
Shatin, New Territories, Hong Kong
Korea, Republic of
Chuncheon Sacred Heart Hospital Recruiting
Gangwon-Do, Korea, Republic of, 200-704
Gangnam Severance Hospital Recruiting
Seoul, Korea, Republic of, 06273
ChungAng University Hospital Recruiting
Seoul, Korea, Republic of, 06973
SMG-SNU Boramae Medical Center Recruiting
Seoul, Korea, Republic of, 156-707
University of Ulsan College of Medicine, Asan Medical Center, Digestive Disease Center Recruiting
Seoul, Korea, Republic of
New Zealand
Auckland Clinical Studies Recruiting
Auckland, New Zealand, 1142
Middlemore Hospital Recruiting
Auckland, New Zealand, 1640
Singapore
National University Hospital; Dept of Gastroenterology & Hepatology Recruiting
Singapore, Singapore, 119228
Singapore General Hospital; Gastroenterology & Hepatology Recruiting
Singapore, Singapore, 169608
Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital Recruiting
Kaohsiung City, Taiwan, 807
Chang Gung Medical Foundation - Kaohsiung Branch Recruiting
Kaohsiung, Taiwan
Taipei Veterans General Hospital Recruiting
Taipei City, Taiwan, 112
Chang Gung Medical Foundation Linkou Branch Recruiting
Taoyuan City, Taiwan, 333
Thailand
Siriraj Hospital; Dept. of Medicine Recruiting
Bangkok, Thailand, 10700
Maharaj Nakorn Chiang Mai Hospital Recruiting
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03038113     History of Changes
Other Study ID Numbers: BP39405
First Posted: January 31, 2017    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Immunologic Factors
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Physiological Effects of Drugs