Primary Efficacy Endpoint and Safety Results of Ibalizumab in a Phase 3 Study of Heavily Treatment-Experienced Patients With Multidrug-Resistant Human Immunodeficiency Virus-1 Infection
Bibliographic record
Abstract
Background. Despite success of combination antiretroviral (ARV) therapy, some patients fail to achieve durable viral suppression due to multidrug-resistant (MDR) human immunodeficiency virus (HIV). Ibalizumab (IBA) is the first long-acting monoclonal antibody HIV-1 entry inhibitor in Phase 3 development for treatment of MDR HIV. IBA was granted Orphan Drug status and Breakthrough Therapy designation by the FDA. Method. TMB-301 is an on-going single arm, 24-week (wk) study of IBA plus optimized background regimen (OBR) in treatment experienced patients with MDR HIV-1. The primary objective was to demonstrate antiviral activity at DAY 14 (7 days after IBA initiation). Patients were monitored for 7 days on a failing ARV regimen (control period). On DAY 7 a 2000-mg IBA loading dose was administered intravenously (IV) as functional monotherapy. The primary efficacy endpoint was the proportion of patients achieving a ≥0.5 log10 decrease in HIV-1 RNA from DAY 7/Baseline (BL) to DAY 14. An OBR with at least one sensitive agent was initiated on DAY 14. IBA was continued at 800 mg IV every two wks for 24 wks on study treatment. Safety and additional efficacy endpoints were evaluated. Result. Forty heavily treatment-experienced patients with MDR HIV were enrolled, mean age of 51 years, 15% female, and 45% non-white. Mean duration of HIV infection was 21 years and 28% were treated with ≥10 previous ARVs. Mean BL CD4+ T-cell count was 161 cells/µL (50% <100 cells/µL) and mean BL viral load (VL) was 5.0 log10 (18% BL VL ≥100,000 copies/mL). Thirty-five percent of patients required an investigational agent in OBR due to extensive resistance. 83% achieved ≥0.5 log10 decrease from BL to DAY 14 on IBA versus 3% during the control period. No treatment-related SAEs or discontinuations were reported during DAY 0–14. End-of-study safety and efficacy assessments are ongoing. Day 14 Intent-to-Treat Results (IBA Added to Stable Failing Regimen) *Protocol deviations affecting analysis: incomplete Day 0 results (n = 1, excluded) and OBR started during control period (n = 1, included). Conclusion. IBA demonstrated statistically significant VL reductions compared to control in MDR HIV patients when added to a failing regimen and was well tolerated. Disclosures. J. Lalezari, TaiMed Biologics USA: Investigator, Research support; W. J. Fessel, TaiMed Biologics USA: Investigator, Research support; S. Schrader, TaiMed Biologics USA: Investigator, Research support; P. Kumar, TaiMed Biologics USA: Investigator, Research support; G. Richmond, TaiMed Biologics USA: Investigator, Research support; C. Marsolais, Theratechnologies Inc: Employee, Salary; S. Weinheimer, TaiMed Biologics USA: Employee, Salary; S. Lewis, TaiMed Biologics USA: Employee, Salary
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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 | 0.000 |
| 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".