| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10019731 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| - To evaluate the safety and tolerability of pegIFNλ as measured by the frequency of SAEs and discontinuations due to AEs - To assess the Hepatitis B e antigen (HBeAg) seroconversion rate at 24 weeks off treatment (Week 72) |
|
| E.2.2 | Secondary objectives of the trial |
| - To evaluate antiviral activity, as determined by the proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS TaqMan HBV Test for use with the High Pure System (HPS) assay - To evaluate mean change from baseline in HBV DNA over time - To assess biochemical response rates - To evaluate the relationship between changes in serum HBV DNA and pegIFNλ PK parameters - To evaluate HBeAg loss and seroconversion - To evaluate quantitative HBeAg levels over time - To characterize the PK of pegIFNλ administered as a fixed dose over 2 dose levels. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1) Signed Written Informed Consent 2) Target Population a) History of CHB infection defined as HBsAg positive at screening and on at least one other occasion ≥ 24 weeks prior to screening; b) Detectable HBeAg and no detectable HBeAb at screening and at least once ≥ 4 weeks prior to screening; c) Serum ALT 1.3 to < 10 x ULN at screening and on at least 1 other occasion within 24 weeks prior to screening, with no value in the intervening period falling below the ULN; d) HBV DNA by PCR ≥ 100,000 copies/mL (17,200 IU/mL) at screening and presence of detectable HBV DNA at least once ≥ 4 weeks prior to screening; e) No prior IFN therapy; f) Prior HBV nucleos(t)ide therapy allowed but not within 30 days prior to screening; g) Thyroid-stimulating hormone (TSH) and/or T4 within 0.8 to 1.2 times the normal limit, or adequately controlled thyroid function as assessed by the investigator; h) Documented baseline retinal exam performed ≤ 1 year of study randomization; any subjects with diabetes, hypertension, or other risk factors for retinal disease per assessment of the investigator can be included with a documented normal eye exam by a licensed ophthalmologist; i) Pre-treatment liver biopsy performed ≤ 2 years prior to study randomization to characterize preexisting liver status. Patients with compensated cirrhosis will be allowed to participate but will be capped at 10%; patients with cirrhosis must not have decompensated liver disease. 3) Age and Reproductive Status a) Men or women, 18 - 70 years of age; b) Contraception Requirements: Women of childbearing potential (WOCBP, see Section 3.3.3 for definition) and sexually active men with female partners who are WOCBP, must use 2 separate forms of contraception from screening throughout the duration of the study. c) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product; d) Women must not be breastfeeding; e) Requirements for male subjects: i) Male subjects (unless vasectomized) with female partners who are WOCBP must agree to inform their females partners of the protocol-specified contraception requirements and pregnancy testing recommendations during treatment and post-treatment, and agree to adhere to these recommendations; ii) Male subjects must confirm that their female sexual partners are not pregnant at the time of screening. |
|
| E.4 | Principal exclusion criteria |
1) Target Disease Exceptions a) Co-infection with HIV, HCV or hepatitis D virus (HDV); b) Other forms of liver disease (eg, alcoholic, autoimmune, biliary disease, hepatic steatosis). 2) Medical History and Concurrent Diseases a) Current evidence of or history of variceal bleeding, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening; b) Current evidence of or history of pancreatitis; c) History of bone marrow or organ transplant or therapy with an immunomodulatory agent, cytotoxic agent, or systemic corticosteroids within 2 months of screening; d) Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening; e) History of hepatocellular carcinoma (HCC) or for patients without a known history, evidence of HCC as documented by abdominal imaging (eg, ultrasound), within 18 months of study randomization; f) Patients with a screening QTcF > 450 msec (males) or > 470 msec (females), based on the average of 3 or more ECGs (ECGs obtained 5 minutes apart while subject is resting in a supine position). g) Patients with other clinically significant ECG abnormalities (indicative of dysarrhythmia, myocardial ischemia or other serious cardiovascular disorder) at the time of screening in the opinion of the investigator; h) Active substance abuse, such as alcohol, or inhaled or injected drugs, as defined by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse (Appendix 1) within 6 months prior to screening. Subjects who are receiving methadone or other substitutive product under medical supervision are eligible. Use of marijuana for medical purpose is allowed; i) Prior or current history of cardiomyopathy or significant ischemic cardiac or cerebrovascular disease, including history of angina, myocardial infarction, interventional procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery); j) Prior or current history of clinically significant hemoglobinopathy or hemolytic anemia; k) Prior or current history of interstitial lung disease or sarcoidosis; l) History of immunologically mediated disease (including, but not limited to, rheumatoid arthritis, inflammatory bowel disease, moderate to severe psoriasis [mild psoriasis is allowed], and systemic lupus erythematosus); m) History of moderate, severe, or uncontrolled psychiatric disease; mild depression controlled at time of screening is allowed; n) Active seizure disorder as defined by either untreated seizure disorder or continued seizure activity within the past year prior to screening despite treatment with anti-seizure medication; o) Has, in the opinion of the investigator, any physical exam findings, laboratory abnormalities, or other medical, social, or psychosocial factors that may negatively impact compliance or subject’s safety by participation in this study; this should include conditions which may affect hematologic parameters such as prior or current history of porphyria cutanea tarda and/or hemophilia. 3) Physical and Laboratory Test Findings a) Hemoglobin < 12.0 g/dL (males) or < 11.0 g/dL (females); b) Platelet count < 90,000/mm�; c) Confirmed creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) ≤ 50 mL/min; d) Total serum bilirubin > 2.5 mg/dL (> 42.75 μmol/L) (unless due to Gilbert’s disease); e) INR > 1.2; f) Serum albumin < LLN; g) Alpha Fetoprotein ≥ 100 ng/mL; h) PTT > 1.5 x ULN; fibrinogen < LLN.
For further details, see study protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoints are to measure: - number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events; - proportion of subjects who achieve HBeAg seroconversion at Week 24 post-dosing (ie, Week 72). During the study, safety assessments are performed weekly during the first month of treatment and every 4 - 8 weeks during study treatment, and every 4 - 12 weeks during post-treatment follow-up. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Beck Depression Inventory II; Fatigue Severity Scale; Interferon antibodies |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined as the date of the last visit for the last subject to complete the study. The last visit is defined as the last post-treatment follow-up subject visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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