ITP-PK-Platelet

Evaluating models for Phase 2 dose and regimen selection in immune thrombocytopenia

Working specification, critical review and reference notebook for evaluating PK–platelet modelling, durable control and immune recovery in ITP.

A small dose escalation followed by two randomized expansion arms could provide serial drug concentrations, B-cell counts and platelet counts for a B-cell depleting agent in ITP. This project asks whether those measurements improve a Phase 2 dose or regimen decision over simpler analyses of the same patients. The clinical objective is durable platelet control with acceptable immune recovery. Prolonged depletion is not assumed to improve a true reset. No PK–platelet model or decision simulation has been run yet.

A second design has only six ITP expansion patients per dose, supported by larger same-agent cohorts in other indications. It asks whether shared PK, peripheral and tissue depletion, and B-cell immunophenotypes can support an ITP dose shortlist, either on pharmacology alone or through an ITP-specific immune-to-platelet model. Healthy naive-cell recovery can be compatible with a durable reset; biological dose support and clinical efficacy support are reported separately.

Documents

• Working specification. Revised after critical review. Defines the clinical endpoint and tradeoffs, compares progressively more complex models, allows benefit to persist after B-cell recovery, and specifies the simulation needed to establish incremental decision value.
• Critical review. Review of the earlier specification, including its equations, biological assumptions and sample-size claims. Preserved as the rationale for the revision.
• Reference notebook. Earlier search and reading notes, with a revision notice and source qualifications. Historical interpretations are not necessarily the conclusions of the revised specification.
• B-cell–platelet relationships. Primary evidence on B-cell recovery, antiplatelet antibodies and tissue reservoirs, with implications for the reset hypothesis and cross-indication dose selection.
• Platelet kinetics gallery. Published count trajectories and response-duration figures across ITP therapies, with local images, source links and notes on interpretation. Includes a list of missing figures.
• Illustrative calculations. Reproduces Section 14’s exact two-arm selection probabilities and simple dose-response calculations; these do not establish PK-model sample savings.