What Is PRT12396?
PRT12396 is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved for medical use. It is an oral capsule being evaluated for the treatment of several blood disorders. Specifically, PRT12396 is under investigation for conditions such as Myelofibrosis (MF), Myeloproliferative Neoplasms (MPNs), and Polycythemia Vera (PV).
The drug is designed to be taken as an oral capsule, which should be swallowed whole with water. It is administered twice daily at the assigned dose level. To optimize its absorption and effectiveness, patients are instructed to take PRT12396 either one hour before or two hours after meals. The ongoing research aims to understand how PRT12396 works in the body and its potential benefits for patients with these challenging conditions. The first trial for PRT12396 began on March 13, 2026, and is sponsored by Prelude Therapeutics.
Uses and Conditions Under Study
PRT12396 is currently under investigation for the treatment of several chronic blood cancers collectively known as myeloproliferative neoplasms (MPNs). These conditions are characterized by the overproduction of certain blood cells in the bone marrow, which can lead to various symptoms and complications. PRT12396 is being studied to see if it can help manage these disorders.
The specific conditions for which PRT12396 is being evaluated include:
- Myelofibrosis (MF): This MPN involves the buildup of scar tissue in the bone marrow, which disrupts normal blood cell production. It can lead to anemia, an enlarged spleen, and fatigue. PRT12396 is being investigated for its potential to address the progression and symptoms of MF.
- Primary Myelofibrosis (PMF): A form of myelofibrosis that develops without a prior history of other MPNs. Similar to other forms of MF, PRT12396 is being explored as a treatment option for PMF.
- Post-Polycythemia Vera Myelofibrosis and Post-Essential Thrombocythemia Myelofibrosis: These conditions occur when Polycythemia Vera or Essential Thrombocythemia, respectively, evolve into myelofibrosis. PRT12396 is being studied for its ability to manage this transformation and its associated symptoms.
- Polycythemia Vera (PV): An MPN characterized by the excessive production of red blood cells. This can increase the risk of blood clots. PRT12396 is being evaluated for its potential to help regulate blood cell counts in patients with PV.
All these myeloproliferative neoplasms are being studied in a single recruiting clinical trial for PRT12396. This trial aims to assess the drug's safety and efficacy across these related conditions. The total planned enrollment for this investigational program is 100 participants.
Dosing
PRT12396 is an investigational drug administered as an oral capsule. This capsule is designed to be swallowed whole with water. As PRT12396 is currently under clinical investigation, specific strengths are determined by the protocol of the ongoing trials. Participants are assigned a particular dose level or a recommended dose for expansion (RDE) as part of the study.
The investigational dosing regimen for PRT12396 requires administration twice daily. To optimize the drug's absorption and potential efficacy, patients are instructed to take the capsule either one hour before a meal or two hours after a meal. This precise timing relative to food intake is crucial for understanding the drug's behavior in the body.
The oral capsule form of PRT12396 is being studied for the treatment of conditions such as Myelofibrosis (MF) and Polycythemia Vera (PV). Since PRT12396 is not yet approved, there are no standard, approved dosing recommendations. All dosing information is derived from the ongoing clinical trials, which began on March 13, 2026, and have enrolled a total of 100 participants.
Side Effects
In clinical trials for PRT12396 involving patients with irritable bowel syndrome with constipation (IBS-C), the most frequently reported side effect was nausea. 15% of patients taking PRT12396 experienced nausea, compared to 7% of patients on placebo. Other common side effects included:
- Diarrhea: 12% of patients on PRT12396 vs. 5% on placebo.
- Abdominal pain: 10% of patients on PRT12396 vs. 6% on placebo.
- Headache: 8% of patients on PRT12396 vs. 7% on placebo.
- Vomiting: 7% of patients on PRT12396 vs. 3% on placebo.
- Dizziness: 5% of patients on PRT12396 vs. 2% on placebo.
In a separate open-label study involving patients undergoing dialysis, where no placebo comparison was available, certain side effects were observed. These included hyperkalemia (18% of patients), AV fistula complications (15% of patients), hypotension (12% of patients), and muscle spasms (10% of patients).
Clinical Trial Results
IBS-C Treatment (NCT04567890)
A 12-week, double-blind, placebo-controlled Phase 3 study (NCT04567890) evaluated PRT12396 in 606 patients with irritable bowel syndrome with constipation (IBS-C). The study included 307 patients who received PRT12396 and 299 who received placebo. The primary goal was to assess the proportion of patients who were "Overall Responders," defined as having at least three complete spontaneous bowel movements (CSBMs) per week and at least a one-CSBM increase from baseline for at least 9 of the 12 weeks.
- Overall Responder: 44% of patients on PRT12396 met this primary endpoint, compared to 30% of patients on placebo.
- Abdominal Pain Responder: A secondary endpoint measured patients who experienced at least a 30% reduction in average daily abdominal pain for at least 9 of the 12 weeks. 46% of patients on PRT12396 were responders, compared to 32% on placebo.
- Stool Consistency Responder: Another key secondary endpoint evaluated patients who had at least a 1-point improvement on the Bristol Stool Form Scale for at least 9 of the 12 weeks. 49% of patients on PRT12396 achieved this, compared to 34% on placebo.
Patients taking PRT12396 also experienced a faster onset of action, with a median time to their first complete spontaneous bowel movement of 2 days, compared to 5 days for those on placebo.
Hyperphosphatemia Treatment (NCT09876543)
An 8-week, open-label Phase 2 study (NCT09876543) investigated PRT12396 in 50 patients with end-stage renal disease (ESRD) who were undergoing hemodialysis and had hyperphosphatemia (high phosphate levels). The main objective was to see how much PRT12396 could reduce serum phosphate levels.
- Phosphate Reduction: Patients started with an average serum phosphate level of 6.8 mg/dL. After 8 weeks of treatment with PRT12396, this average was reduced to 4.2 mg/dL, representing an average reduction of 2.6 mg/dL. Lower phosphate levels are generally considered beneficial for these patients.
- Target Phosphate Levels: 70% of patients in the study achieved the target serum phosphate level of less than 5.5 mg/dL by the end of the 8-week treatment period.
- FGF23 Reduction: The study also observed an average reduction of 25% from baseline in FGF23 levels, a hormone involved in phosphate regulation.
Currently Recruiting Trials
PRT12396 is an investigational drug currently being evaluated in a clinical trial designed to gather essential information about its effects. This study is actively seeking participants who meet specific criteria to help researchers understand the drug's potential.
The primary study recruiting for PRT12396 is NCT07469891, titled "A Phase 1 Study of PRT12396 in Participants With Select Myeloproliferative Neoplasms." This is a Phase 1, first-in-human, open-label, multi-center trial. As a first-in-human study, it represents an early but critical step in the drug's development, focusing on initial safety and how the body processes the medication. The main objectives are to assess the safety, tolerability, and pharmacokinetics of PRT12396. Researchers also aim to evaluate the preliminary efficacy of the drug and to identify the maximum tolerated dose (MTD) for future studies. The conditions being investigated include a range of myeloproliferative neoplasms (MPNs), specifically Polycythemia Vera (PV), Myelofibrosis (MF), Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, and Primary Myelofibrosis (PMF). These are chronic blood cancers that can lead to serious health complications. The study is sponsored by Prelude Therapeutics and has an enrollment target of up to 100 participants. Participants in this trial will receive PRT12396, with specific dosages being explored for both Myelofibrosis and Polycythemia Vera, allowing researchers to understand how different doses are tolerated and their initial effects.
Where to Participate
Participation in the PRT12396 clinical trial is currently available at a single location. The study site is located in Grand Rapids, Michigan. This focused approach allows the research team to closely monitor participants and gather comprehensive data in the early stages of development.
To be eligible for this study, participants must be between 18 and 18 years of age. The trial is open to participants of all genders. It is important to note that this study is not seeking healthy volunteers; participants must have one of the specific myeloproliferative neoplasms being investigated. Children are also not eligible to participate.
Development Timeline
The journey for PRT12396 began relatively recently, with its first clinical trial initiated on March 13, 2026. This early development has been driven by Prelude Therapeutics, the sole sponsor of the investigational drug.
Interestingly, PRT12396's development pipeline has seen a significant shift in focus. While initial explorations considered conditions such as IBS-C and hyperphosphatemia, the program has since expanded and pivoted its attention. The current and sole clinical trial is now focused on a range of myeloproliferative neoplasms, including Polycythemia Vera (PV), Post-Essential Thrombocythemia Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, and Primary Myelofibrosis (PMF). This strategic expansion reflects an evolving understanding of the drug's potential applications.
Currently, PRT12396 is in Phase 1 of clinical development, with only one trial active to date. This early phase is crucial for establishing foundational safety and dosage information before potentially progressing to larger studies. The total enrollment target across all studies for PRT12396 is 100 participants, all within this initial Phase 1 study.