Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study
Bibliographic record
Abstract
Abstract Chronic human immunodeficiency virus type 1 (HIV-1) disease results in immune exhaustion and dampened T cell responses, and programmed cell death 1 (PD-1) inhibitors offer a potential approach to enable viral control without antiretroviral therapy (ART) through reversal of these effects. Budigalimab is an investigational humanized anti–PD-1 monoclonal antibody. Multiple intravenous (IV) low doses of budigalimab (Stage 1: 2 mg n = 10, 10 mg n = 10, placebo n = 5, two doses every 4 weeks; Stage 2: 10 mg n = 11, placebo n = 5, four doses every 2 weeks (Q2W)) were assessed in people living with HIV (PLWH; n = 41) in a randomized, double-blind, multicenter, placebo-controlled phase 1 study with an analytical treatment interruption (ATI) to identify an efficacious regimen with a favorable safety profile in PLWH. The primary endpoints were safety, tolerability and pharmacokinetics. Demographics and baseline characteristics were balanced across treatment groups, except for sex, which was mostly male. All participants identified as cisgender. Budigalimab was well tolerated for up to 44 weeks, with 29 of 41 participants experiencing an adverse event (AE), including 2 participants who each experienced one grade 1 reversible immune-related AE (thyroiditis, hyperthyroidism). Three grade 3 AEs were reported by two participants and one serious AE by one participant; none were deemed related to treatment. IV budigalimab 10 mg Q2W resulted in a slight accumulation of drug in serum, with concentrations remaining above the estimated concentration required for near-complete (>95%) PD-1 receptor saturation on CD8 + T cells for ~10 weeks in peripheral blood. In an exploratory efficacy analysis of a 12-week ATI initiated with the first of four 10 mg Q2W doses, 6 of 11 participants experienced a delayed rebound with a relatively low viral peak and/or off-ART viral control (<200 copies ml −1 ) for ≥6 weeks during ATI, with 2 sustaining ART-free viral control to study end (204−252 days). The study achieved prespecified endpoints, supporting further evaluation of budigalimab in PLWH in a phase 2 study. ClinicalTrials.gov identifier: NCT04223804 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".