ITP-PK-Platelet

Selecting a Phase 2 dose for a B-cell depleting agent in immune thrombocytopenia

Index of the documents in the ITP-PK-Platelet project: the working specification and its literature review.

A B-cell depleting agent has been given to a few dozen patients with immune thrombocytopenia in a dose escalation and a single expansion cohort, with serial drug concentrations, B-cell counts and platelet counts. Can a model of those three time courses select the Phase 2 dose? The literature has the platelet half of that model and the B-cell half, in separate places and for separate drugs, and nothing that joins them in this disease. The references document widens the search to every ITP drug that blocks antibody-mediated platelet destruction, and asks why the join is missing. Nothing has been fit here yet.

Documents

• Working specification. Section 2 gives the ITP endpoint definitions from the IWG 2009 consensus paper. Then the model, the data it requires, the identifiability problems, the dose selection rule, and the simulation study that scores the rule against picking the highest safe dose. Section 19 gives the reasons no such model has been published, split into those that apply here and those that do not, with a table of every attempt. Its In brief section is one screen and says what the rest argues.
• References. The literature review that opens with what exists and what does not, then the reading queue in order, then a marker on every source recording whether the specification’s use of it has been checked, plus the FDA, EMA and PMDA reviews of the three ITP drugs that block platelet destruction, read in full, and a table of the TPO-RA PK-platelet models the specification borrows from. Six sources have been read; the rest are ❌.