Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias – pilot study protocol
Bibliographic record
Abstract
INTRODUCTION: gene and can exhibit phenotypic similarities to membranopathies. Current treatment options for these conditions, apart from splenectomy, are primarily supportive. Mitapivat, a novel pyruvate kinase (PK) activator, has demonstrated efficacy in increasing haemoglobin levels and reducing haemolysis in patients with PK deficiency, thalassemia, sickle cell disease and a mouse model of hereditary spherocytosis. METHODS AND ANALYSES: throcyte membranopathies (SATISFY) is a prospective, multicentre, single-arm phase two trial involving approximately 25 adult patients (≥18 years) diagnosed with a membranopathy or CDA II. During the 8-week dose escalation period, subjects will receive an initial dose of 50 mg mitapivat two times per day and may increase to 100 mg two times per day at week 4 based on the safety and changes in haemoglobin levels. Patients tolerating mitapivat well may be eligible to continue in two consecutive 24-week fixed dose periods.The primary objective of this study is to evaluate the safety of mitapivat, assessed through the occurrence of treatment-emergent adverse events. Secondary objectives include assessing the effects of mitapivat on haemoglobin levels, haemolysis, erythropoiesis, patient-reported outcome measures and spleen size.SATISFY aims to assess the safety and efficacy of mitapivat in adult patients with red blood cell membranopathies and CDA II, with the aim of establishing proof-of-concept in patients living with these rare conditions. ETHICS AND DISSEMINATION: NCT05935202/CTIS:2023-503271-24-01. Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT05935202. CTIS:2023-503271-24-01. Registered 07-July-2023. Protocol number: 2.1. https://clinicaltrials.gov/study/NCT05935202.
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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 | 0.018 | 0.012 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.019 | 0.004 |
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".