Phase 4
Completed N=751
Efficacy & Safety of Tenofovir Disoproxil Fumarate (TDF) Plus Peginterferon α-2a (Peg-IFN) Versus TDF or Peg-IFN Monotherapy in Chronic Hepatitis B
Source: ClinicalTrials.gov NCT01277601 ↗Enrolled (actual)
751
Serious AEs
7.9%
Results posted
Sep 2015
Primary outcomePrimary: Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone — 9.05; 0.00; 2.84 percentage of participants — p=< 0.001
Summary
The primary objective of this study is to evaluate the efficacy of tenofovir disoproxil fumarate (TDF) plus peginterferon α-2a (Peg-IFN) combination therapy for 48 weeks versus standard of care TDF monotherapy or Peg-IFN monotherapy for 48 weeks in non-cirrhotic adults with chronic hepatitis B virus (HBV) as determined by loss of hepatitis B surface antigen (HBsAg).
The study will consist of 2 phases for participants in the TDF+Peg-IFN 48 Weeks, TDF 48 Weeks + Peg-IFN 16 Weeks, and Peg-IFN 48 Weeks groups. Following an initial 48 weeks of treatment, participants in these groups will be monitored for 24 weeks for signs of worsening HBV, and those meeting TDF retreatment and flare management criteria will be eligible to receive TDF monotherapy during a retreatment phase, up to Week 120.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With 48 Weeks of TDF Plus Peg-IFN Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone |
9.05; 0.00; 2.84 | < 0.001 sig |
| SECONDARY Percentage of Participants With HBsAg Loss at Week 72 Following Treatment With TDF (48 Weeks) Plus Peg-IFN (16 Weeks) Combination Versus Peg-IFN Alone for 48 Weeks or TDF Alone |
2.83; 0.00; 2.84 | — |
| SECONDARY Percentage of Participants With HBsAg Loss at Weeks 96 and 120 |
9.69; 3.49; 0.00; 2.84; 10.36; 3.49 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion at Weeks 72, 96, and 120 |
8.05; 0.56; 0.00; 2.87; 8.05; 0.56 | — |
| SECONDARY Percentage of Participants With HBeAg Loss and Seroconversion at Week 72 |
35.5; 15.6; 32.8; 15.9; 14.7; 32.8 | — |
| SECONDARY Percentage of Participants With HBeAg Loss and Seroconversion at Week 96 |
43.2; 20.3; 45.5; 14.8; 18.3; 37.8 | — |
| SECONDARY Percentage of Participants With HBeAg Loss and Seroconversion at Week 120 |
38.6; 25.0; 37.5; 23.1; 20.2; 33.3 | — |
| SECONDARY Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 72 |
15.3; 26.2; 14.5; 15.1; 84.9; 11.7 | — |
| SECONDARY Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 96 |
21.7; 68.0; 15.7; 80.2; 83.8; 13.9 | — |
| SECONDARY Percentage of Participants With Virological Response (HBV DNA < 117 IU/mL) at Week 120 |
32.4; 81.3; 18.8; 83.5; 82.2; 13.2 | — |
| SECONDARY Percentage of Participants With Normal ALT at Week 72 |
42.1; 18.3; 40.7; 18.2; 47.6; 35.0 | — |
| SECONDARY Percentage of Participants With Normal ALT at Week 96 |
43.2; 42.9; 34.1; 46.1; 48.1; 34.7 | — |
| SECONDARY Percentage of Participants With Normal ALT at Week 120 |
39.2; 54.5; 30.4; 48.7; 48.6; 30.9 | — |
| SECONDARY Percentage of Participants Who Required Retreatment |
60.2; 62.5; 63.2 | — |
Eligibility Criteria
Inclusion Criteria
- Adults (age 18-75) with chronic HBV (positive for serum hepatitis B surface antigen (HBsAg) or HBV DNA for at least 6 months) prior to baseline
- Anti-HBV treatment-naive adults; adults who have taken oral anti-HBV nucleoside therapy with the last dose ≥ 24 weeks prior to screening are also eligible.
- Positive or negative for hepatitis B e antigen (HBeAg)
- HBV DNA ≥ 20, 000 IU/ml (HBeAg-positive participants) and ≥ 2,000 IU/ml (HBeAg-negative participants)
- Alanine aminotransferase (ALT) > 54 U/L and ≤ 400 U/L for men and > 36 U/L and ≤ 300 U/L for women
- Creatinine clearance ≥ 70 mL/min
- Negative serum pregnancy test for females of childbearing potential
- Sexually active females of childbearing potential must agree to use a protocol-recommended method of contraception throughout the study and for 30 days following the last dose of study medication
- Lactating females must agree to discontinue nursing before initiation of study investigational medicinal product
Exclusion Criteria
- Known bridging fibrosis or cirrhosis and/or decompensated liver disease
- Evidence of hepatocellular carcinoma
- Significant kidney, heart, lung, neurological, autoimmune disease, or bone disease (eg, osteomalacia,chronic osteomyelitis, osteogenesis imperfecta, osteochondrosis, multiple bone fractures)
- Absolute neutrophil count < 1, 500/mm^3, platelet < 100,000/mm^3, hemoglobin < 10 g/dL (female) or < 11 g/dL (male)
- History of severe depression or severe psychiatric disease
- Thyroid dysfunction
- Coinfection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
- Pregnant
Data sourced from ClinicalTrials.gov (NCT01277601). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.