Peginterferon alpha-2a add-on to siRNA JNJ-73763989 in untreated patients with HBeAg-positive chronic hepatitis B virus (HBV) infection: the phase 2 REEF-IT study
Bibliographic record
Abstract
Background In the hepatitis B e antigen positive (HBeAg+) chronic infection disease phase, approved treatments have limited effects on hepatitis B surface antigen (HBsAg) and HBeAg. Objective The phase 2 REEF-IT study ( NCT04439539 ) assessed safety, efficacy and pharmacokinetics of pegylated interferon-α2a (PegIFN-α2a) add-on to JNJ-73763989 (JNJ-3989)±bersacapavir+nucleos(t)ide analogues (NA) in not currently treated, HBeAg+chronic hepatitis B. Design Participants received JNJ-3989 (200 mg every 4 weeks)+NA±bersacapavir (250 mg daily) for 36–52 weeks (induction) followed by 12 weeks of PegIFN-α2a (180 µg weekly) add-on. The primary endpoint was the proportion of participants with HBsAg seroclearance 24 weeks after stopping all treatment including NA. Changes in viral markers, safety and pharmacokinetics were assessed. Results 49/54 (91%) enrolled participants completed the study; 52% were male, with mean age of 33.6 years. No participant achieved the primary endpoint; one met NA completion criteria. 11/54 (20.4%) participants achieved HBsAg seroclearance at least once, 6 of them maintained it until Follow-up Week 48 (FUW48). Overall mean (SE) change from baseline in HBsAg of –2.85 (0.13), –3.61 (0.18) and –2.63 (0.26)log 10 IU/mL were observed at end of induction, end of treatment and FUW48. 16/53 (30.2%) participants reached HBeAg seroclearance at least once; 12 maintained it until FUW48. Similar proportions of participants experienced an adverse event (AE) during induction (83.3%), PegIFN-α2a add-on (85.7%) and follow-up (64.7%). There were no deaths or serious AEs; two participants discontinued PegIFN-α2a. Conclusions In this population, adding PegIFN-α2a increased HBsAg declines after reductions by JNJ-3989; 20.4% achieved HBsAg seroclearance at least once. Treatment was generally safe with acceptable tolerability. Trial registration number NCT04439539 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".