ErythrocytosisPhase 2NCT07895966
Phase IIA Study of Belzutifan in EPAS1-, EGLN1-, or VHL-Mutant Erythrocytosis
A Phase 2 study testing Belzutifan in people with Erythrocytosis and Pulmonary Hypertension, run by University of Utah at 1 site in United States.
Trial summary
Some people develop erythrocytosis, a condition characterized by having too many red blood cells, because of inherited changes (mutations) in genes such as EPAS1, EGLN1, or VHL. These genes are involved in the body's oxygen-sensing pathway and can cause the body to produce excess red blood cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erythrocytosis, Pulmonary Hypertension, Thrombosis
- What is being tested?
- Belzutifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Male or female subject aged ≥ 18 years old with erythrocytosis (Hb>18g/dL in male and Hb>16g/dL in a female>18 years old and Hb>0.5g/dL the upper limit of normal range for their age) with a known EPAS1, EGLN1, or VHL mutation 2. Neutrophils>1.5 k/uL, Hb>10g/dL, platelet count >100x106 without transfusions 3. CrCl>30using Cockcroft Gault; total bilirubin <1.5x ULN (<3xULN in patients with Gilbert's disease), and alkaline phosphatase<2.5x ULN 4. Females or male patients with a female partner of childbearing potential must agree to effective methods of contraception 5. Possible iron deficiency needs to be evaluated and if present, corrected. Then, baseline Hb level obtained at least after 4 weeks of correction of iron deficiency 6. Able to swallow oral medications 7. Have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 (refer to appendix). Evaluation of ECOG is to be performed within 10 days prior to the first dose of study intervention.
Who cannot join
- Any of the following:
- A pulse oximeter reading <92% at rest, or
- Requires intermittent supplemental oxygen, or
- Requires chronic supplemental oxygen
- Clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤3 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
- Moderate to severe hepatic impairment (Child-Pugh B or C)
Show all 23Show fewer
- Received colony-stimulating factors (e.g., G-CSF, GM-CSF or recombinant EPO) ≤28 days prior to the first dose of study intervention
- Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
- Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption)
- Known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan) formulations
- Received prior treatment with belzutifan or another HIF-2α inhibitor
- Received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤5 half lives before [randomization/allocation]
- Major surgery ≤3 weeks prior to first dose of study intervention Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
- Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g., bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study Note: A current list of strong/moderate inducers of CYP3A4 can be found at the following website: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
- Is currently participating in a study of an investigational agent or is currently using an investigational device Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent\
- Active infection requiring systemic therapy
- Active TB
- Diagnosis of immunodeficiency
- History or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's ability to cooperate with the requirements of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has received therapeutic phlebotomy within 3 months of starting therapy
- Uncorrected iron deficiency
- Diagnosed with another form of erythrocytosis such as polycythemia vera, EPO or EPOR mutations, high oxygen affinity Hb mutations, current smoking, testosterone use, untreated/unsupported heart or lung disease, Eisenmenger complex
- Pregnant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112
Josef T. Prchal, MD, 801-585-0236, josef.prchal@hsc.utah.edu
Jihyun Song, PhD, 801-587-4682, jihyun.song@utah.edu
About this study
Official title: Phase IIA Study to Evaluate the Efficacy of HIF2a Inhibitor Belzutifan in Patients With Erythrocytosis by EPAS1 (HIF2a), EGLN1 (PHD2), or VHL Mutations
Some people develop erythrocytosis, a condition characterized by having too many red blood cells, because of inherited changes (mutations) in genes such as EPAS1, EGLN1, or VHL. These genes are involved in the body's oxygen-sensing pathway and can cause the body to produce excess red blood cells. High red blood cell counts can increase the risk of symptoms and complications, including headaches, blood clots, and cardiovascular problems.
This study will evaluate whether belzutifan, a medication that blocks the activity of HIF-2α, can reduce red blood cell production and improve blood counts in patients with erythrocytosis caused by these genetic mutations. Participants will receive belzutifan and undergo regular clinical assessments and laboratory testing to monitor treatment response and safety. The results of this study may provide a new targeted treatment option for patients with hereditary erythrocytosis caused by abnormalities in the oxygen-sensing pathway.
- Conditions
- Erythrocytosis, Pulmonary Hypertension, Thrombosis
- Being tested
- Belzutifan
- Keywords
- erythrocytosis, HIF, VHL, EGLN1, EPAS1, belzutifan
- Medical subject headings
- Polycythemia, Hypertension, Pulmonary, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Belzutifan is an oral hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor administered to patients with erythrocytosis caused by pathogenic mutations in EPAS1, EGLN1, or VHL. Treatment is intended to suppress abnormal HIF signaling and reduce excessive red blood cell production.
| Study group | Role | What they receive |
|---|---|---|
| Belzutifan Treatment | Experimental | Not described Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalization of hemoglobin
Either normalizing Hb or lowering of patient Hb by at least 1.5g/dL from the patient's baseline by 12 weeks of therapy.
Measured: 12 weeks
Secondary outcomes (1)
Amelioration of prothrombotic milieu and pulmonary hypertension
- Amelioration of prothrombotic milieu by normalization of transcripts of HIF regulated genes
- Amelioration of pulmonary hypertension
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ErythrocytosisStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Josef Prchal, University of Utah
- Investigators
- Josef T. Prchal, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07895966
- Sponsor's protocol ID
- 00205638
- Status last verified
- Sep 2026
- First submitted
- 19 Oct 2026
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified individual participant data will not be made publicly available. Study findings will be reported in aggregate form through scientific presentations and publications.
Publications
Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425.
PubMed 34818478
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIA Study to Evaluate the Efficacy of HIF2a Inhibitor Belzutifan in Patients With Erythrocytosis by EPAS1 (HIF2a), EGLN1 (PHD2), or VHL Mutations
- ClinicalTrials.gov ID
- NCT07895966
- Acronym / sponsor ID
- 00205638
- Conditions
- Erythrocytosis, Pulmonary Hypertension, Thrombosis
- Keywords
- erythrocytosis, HIF, VHL, EGLN1, EPAS1, belzutifan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 26 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some people develop erythrocytosis, a condition characterized by having too many red blood cells, because of inherited changes (mutations) in genes such as EPAS1, EGLN1, or VHL. These genes are involved in the body's oxygen-sensing pathway and can cause the body to produce excess red blood cells. High red blood cell counts can increase the risk of symptoms and complications, including headaches, blood clots, and cardiovascular problems.
This study will evaluate whether belzutifan, a medication that blocks the activity of HIF-2α, can reduce red blood cell production and improve blood counts in patients with erythrocytosis caused by these genetic mutations. Participants will receive belzutifan and undergo regular clinical assessments and laboratory testing to monitor treatment response and safety. The results of this study may provide a new targeted treatment option for patients with hereditary erythrocytosis caused by abnormalities in the oxygen-sensing pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belzutifan Treatment | Experimental | Drug: Belzutifan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Male or female subject aged ≥ 18 years old with erythrocytosis (Hb>18g/dL in male and Hb>16g/dL in a female>18 years old and Hb>0.5g/dL the upper limit of normal range for their age) with a known EPAS1, EGLN1, or VHL mutation 2. Neutrophils>1.5 k/uL, Hb>10g/dL, platelet count >100x106 without transfusions 3. CrCl>30using Cockcroft Gault; total bilirubin <1.5x ULN (<3xULN in patients with Gilbert's disease), and alkaline phosphatase<2.5x ULN 4. Females or male patients with a female partner of childbearing potential must agree to effective methods of contraception 5. Possible iron deficiency needs to be evaluated and if present, corrected. Then, baseline Hb level obtained at least after 4 weeks of correction of iron deficiency 6. Able to swallow oral medications 7. Have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 (refer to appendix). Evaluation of ECOG is to be performed within 10 days prior to the first dose of study intervention.
Key exclusion criteria (23 listed)
- Any of the following:
- Clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤3 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted
- Moderate to severe hepatic impairment (Child-Pugh B or C)
- Received colony-stimulating factors (e.g., G-CSF, GM-CSF or recombinant EPO) ≤28 days prior to the first dose of study intervention
- Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelzutifanBelzutifan is an oral hypoxia-inducible factor 2 alpha (HIF-2α) inhibitor administered to patients with erythrocytosis caused by pathogenic mutations in EPAS1, EGLN1, or VHL. Treatment is intended to suppress abnormal HIF signaling and reduce excessive red blood cell production. | Drug | Belzutifan Treatment |
Primary outcome
Normalization of hemoglobin
Time frame: 12 weeks
Either normalizing Hb or lowering of patient Hb by at least 1.5g/dL from the patient's baseline by 12 weeks of therapy.
1 secondary outcome
Amelioration of prothrombotic milieu and pulmonary hypertension
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 34818478Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, Oudard S, Else T, Maranchie JK, Welsh SJ, Thamake S, Park EK, Perini RF, Linehan WM, Srinivasan R; MK-6482-004 Investigators. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease. N Engl J Med. 2021 Nov 25;385(22):2036-2046. doi: 10.1056/NEJMoa2103425.
- Individual participant dataSharing planned: Undecided. De-identified individual participant data will not be made publicly available. Study findings will be reported in aggregate form through scientific presentations and publications.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Josef T. Prchal, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belzutifan in people with Erythrocytosis and Pulmonary Hypertension, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Josef T. Prchal, MD (801-585-0236, josef.prchal@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normalization of hemoglobin (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07895966, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.