JAK2 MutationPhase 1NCT07249840
Ropeginterferon for High Risk JAK2 Clonal Hematopoiesis
A Phase 1 study testing Ropeginterferon in people with JAK2 Mutation, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if the drug ropeginterferon alfa-2b can be used safely to treat patients with a JAK2 mutation and high risk features, but do not yet have a myeloproliferative neoplasm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- JAK2 Mutation
- What is being tested?
- Ropeginterferon
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2026to Aug 2030
- Phase
- Phase 1
- 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
- Adults age 18 years or older
- Evidence of JAK2 V617F clonal hematopoiesis of indeterminate potential, as defined by a JAK2 V617F mutation detected on quantitative PCR. By definition, these patients do NOT have a diagnosis of an MPN, and must have at least one additional high-risk feature.
- Have high-risk clinical/laboratory features, as defined as at least ONE of the following criteria:
- Patients with a venous or arterial thrombotic event within 1 year prior to or any time after diagnosis of JAK2 clonal hematopoiesis
- Patients with elevated laboratory parameters above normal limits at screening, but not meeting criteria for an MPN by WHO 2016 criteria. This would include patients with elevated laboratory parameters but an otherwise normal bone marrow biopsy.
- White blood cell count > 10 K/uL OR
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- Hemoglobin > 16 g/dL in women and > 16.5 g/dL in men; OR hematocrit >48% for women and >49% for men OR
- Platelets >400 K/uL
- Patients with JAK2 VAF >20%
- Willing to have a bone marrow biopsy at study entry to exclude an MPN diagnosis. Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal hematopoiesis as determined by multi-institutional hematopathology review. A historical bone marrow biopsy is allowed if within 3 months of C1D1 and records and pathology can be obtained. In cases where the bone marrow biopsy results are uncertain, study eligibility should be discussed with the PI. All patients will have an erythropoietin level drawn to rule out a PV diagnosis by WHO 2016 criteria.
- Must have adequate organ function as demonstrated by the following:
- ALT (SGPT) and AST (SGOT) ≤ 2.5x upper limit of normal (ULN),
- Direct bilirubin ≤ 1.5 x ULN
- eGFR >60 mL/min
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- Platelets ≥100,000/mcL
- ECOG performance status (PS) ≤ 3
- Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months of C1D1 are eligible for this trial.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
- The effects of ropeginterferon on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ropeginterferon administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Meeting WHO 2016 criteria for a MPN.
- Pregnant or lactating.
- Any active malignancy in the past 2 years prior to C1D1, with the exception of non-melanoma skin cancer, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis. Any malignancy treated with curative intent and no evidence for active disease in the last 2 years are eligible.
- Evidence of severe retinopathy or clinically relevant ophthalmologic disorder.
- Participation in an investigational drug or device trial within 2 weeks prior to C1D1
- Documented autoimmune disease at screening or in the medical history which is active and serious
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- History of significant and clinically relevant psychiatric illnesses, including prior suicide attempts or risk of suicide on screening
- History of thyroid dysfunction not adequately controlled
- History of major organ transplantation
- History of uncontrolled severe seizure disorder
- Participants who are receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ropeginterferon.
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, 1 recruiting
- Recruiting
Mass General Brigham
Boston, Massachusetts, 02115
Chi-Joan How How, 617-732-5190, jhow@bwh.harvard.edu
About this study
Official title: Pilot Study of Ropeginterferon for Patients With JAK2 V617F Clonal Hematopoiesis and High-Risk Features
The goal of this clinical trial is to learn if the drug ropeginterferon alfa-2b can be used safely to treat patients with a JAK2 mutation and high risk features, but do not yet have a myeloproliferative neoplasm. The main questions it aims to answer are:
- Can we enroll 12 patients with JAK2 mutations and high risk features without a myeloproliferative neoplasm on a clinical trial evaluating the drug ropeginterferon?
- Is ropeginterferon safe to use in these patients?
Participants will:
- Receive ropeginterferon as an injection under the skin once every 4 weeks
- Visit the clinic every 1-3 months for checkups and tests
Read the detailed description
Myeloproliferative neoplasms (MPNs) are driven by dysregulation of the JAK/STAT signaling pathway, most commonly due to the JAK2 V617F mutation. Recent data suggest that JAK2 mutations can arise decades before overt disease, representing an early "precursor" state known as JAK2 clonal hematopoiesis. Individuals with JAK2 clonal hematopoiesis have increased risks of both thrombosis and future MPN development. Early intervention to reduce the malignant clone may therefore improve long-term outcomes.
This is a prospective cohort feasibility study evaluating ropeginterferon alfa-2b in patients with JAK2 V617F clonal hematopoiesis and high-risk features for thrombosis or progression. Participants will receive ropeginterferon by subcutaneous injection every 4 weeks for up to 2 years.
The primary objective is to assess feasibility (enrollment of 12 patients within 2 years) and evaluate the safety and tolerability of ropeginterferon. Secondary objectives include assessing molecular response rates of thrombosis, bleeding, quality of life, and progression to myeloproliferative neoplasm (MPN).
every 6 months through year 2, and again at years 3 and 4 to evaluate durability of response.
- Conditions
- JAK2 Mutation
- Being tested
- Ropeginterferon
- Keywords
- Clonal hematopoiesis, CHIP, JAK2, Myeloproliferative neoplasm
- Medical subject headings
- Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RopeginterferonDrug
Patients will receive Ropeginterferon
| Study group | Role | What they receive |
|---|---|---|
| Ropeginterferon | Experimental | Not described Receives: Drug: Ropeginterferon |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients consented and enrolled within 2 years of study opening
Primary outcome is feasibility, or feasibility of enrolling 12 patients with high-risk JAK2 clonal hematopoiesis onto a clinical trial with ropeginterferon treatment within 2 years of study opening.
Measured: 2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Safety and tolerability of ropeginterferon in patients with JAK2 clonal hematopoiesis and high-risk features.
Measured: 2 years
Secondary outcomes (5)
Number of patients with decrease of JAK2 V617F variant allele fraction to undetectable levels if baseline VAF was <10% or decrease of JAK2 V617F VAF by at least 50% if baseline VAF was >10%
Molecular response
Measured: 2 years
Rates of arterial and venous thrombosis
Measured: 2 years
Rates of bleeding
Measured: 2 years
Patient reported quality of life as measured by the Patient's Impression of Global Change (PGIC) and Patient-Reported Outcomes Measurement Information System 29-item Health Profile (PROMIS-29)
Measured: 2 years
Rates of progression to overt MPN
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2025
- Study start24 Jul 2026
- Primary completionAug 2030 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for JAK2 MutationStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chi-Joan How, MD, Brigham and Women's Hospital
- Investigators
- Chi-Joan How, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07249840
- Sponsor's protocol ID
- 25-566
- Status last verified
- Jul 2026
- First submitted
- 16 Oct 2025
- Last updated
- 28 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Ropeginterferon for Patients With JAK2 V617F Clonal Hematopoiesis and High-Risk Features
- ClinicalTrials.gov ID
- NCT07249840
- Acronym / sponsor ID
- 25-566
- Conditions
- JAK2 Mutation
- Keywords
- Clonal hematopoiesis, CHIP, JAK2, Myeloproliferative neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 24 Jul 2026 (actual)
- Primary completion
- Aug 2030 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 25 Nov 2025 (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.
The goal of this clinical trial is to learn if the drug ropeginterferon alfa-2b can be used safely to treat patients with a JAK2 mutation and high risk features, but do not yet have a myeloproliferative neoplasm. The main questions it aims to answer are:
- Can we enroll 12 patients with JAK2 mutations and high risk features without a myeloproliferative neoplasm on a clinical trial evaluating the drug ropeginterferon?
- Is ropeginterferon safe to use in these patients?
Participants will:
- Receive ropeginterferon as an injection under the skin once every 4 weeks
- Visit the clinic every 1-3 months for checkups and tests
Detailed description
Myeloproliferative neoplasms (MPNs) are driven by dysregulation of the JAK/STAT signaling pathway, most commonly due to the JAK2 V617F mutation. Recent data suggest that JAK2 mutations can arise decades before overt disease, representing an early "precursor" state known as JAK2 clonal hematopoiesis. Individuals with JAK2 clonal hematopoiesis have increased risks of both thrombosis and future MPN development. Early intervention to reduce the malignant clone may therefore improve long-term outcomes.
This is a prospective cohort feasibility study evaluating ropeginterferon alfa-2b in patients with JAK2 V617F clonal hematopoiesis and high-risk features for thrombosis or progression. Participants will receive ropeginterferon by subcutaneous injection every 4 weeks for up to 2 years.
The primary objective is to assess feasibility (enrollment of 12 patients within 2 years) and evaluate the safety and tolerability of ropeginterferon. Secondary objectives include assessing molecular response rates of thrombosis, bleeding, quality of life, and progression to myeloproliferative neoplasm (MPN).
every 6 months through year 2, and again at years 3 and 4 to evaluate durability of response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ropeginterferon | Experimental | Drug: Ropeginterferon |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Adults age 18 years or older
- Evidence of JAK2 V617F clonal hematopoiesis of indeterminate potential, as defined by a JAK2 V617F mutation detected on quantitative PCR. By definition, these patients do NOT have a diagnosis of an MPN, and must have at least one additional high-risk feature.
- Have high-risk clinical/laboratory features, as defined as at least ONE of the following criteria:
- Willing to have a bone marrow biopsy at study entry to exclude an MPN diagnosis. Screening bone marrow biopsy must not be diagnostic of any overt hematologic malignancy by morphologic assessment and must be consistent with a diagnosis of clonal hematopoiesis as determined by multi-institutional hematopathology review. A historical bone marrow biopsy is allowed if within 3 months of C1D1 and records and pathology can be obtained. In cases where the bone marrow biopsy results are uncertain, study eligibility should be discussed with the PI. All patients will have an erythropoietin level drawn to rule out a PV diagnosis by WHO 2016 criteria.
- Must have adequate organ function as demonstrated by the following:
Key exclusion criteria (12 listed)
- Meeting WHO 2016 criteria for a MPN.
- Pregnant or lactating.
- Any active malignancy in the past 2 years prior to C1D1, with the exception of non-melanoma skin cancer, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis. Any malignancy treated with curative intent and no evidence for active disease in the last 2 years are eligible.
- Evidence of severe retinopathy or clinically relevant ophthalmologic disorder.
- Participation in an investigational drug or device trial within 2 weeks prior to C1D1
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 |
|---|---|---|
| RopeginterferonPatients will receive Ropeginterferon | Drug | Ropeginterferon |
Primary outcome
Number of patients consented and enrolled within 2 years of study opening
Time frame: 2 years
Primary outcome is feasibility, or feasibility of enrolling 12 patients with high-risk JAK2 clonal hematopoiesis onto a clinical trial with ropeginterferon treatment within 2 years of study opening.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 2 years
Safety and tolerability of ropeginterferon in patients with JAK2 clonal hematopoiesis and high-risk features.
5 secondary outcomes
Number of patients with decrease of JAK2 V617F variant allele fraction to undetectable levels if baseline VAF was <10% or decrease of JAK2 V617F VAF by at least 50% if baseline VAF was >10%
Time frame: 2 years
Rates of arterial and venous thrombosis
Time frame: 2 years
Rates of bleeding
Time frame: 2 years
Patient reported quality of life as measured by the Patient's Impression of Global Change (PGIC) and Patient-Reported Outcomes Measurement Information System 29-item Health Profile (PROMIS-29)
Time frame: 2 years
Rates of progression to overt MPN
Time frame: 2 years
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 28 Jul 2026.
Related trials for JAK2 Mutation
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Flonoltinib Maleate Oral Regimens in Patients With Myelofibrosis
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Ruxolitinib in Treating Patients With Hypereosinophilic Syndrome or Primary Eosinophilic Disorders
BCR-JAK2 Fusion Protein Expression, Blasts 20 Percent or Less of Peripheral Blood White Cells
RecruitingObservational study
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Active, not recruitingPhase 2
Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
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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.
Chi-Joan How principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ropeginterferon in people with JAK2 Mutation, run by Brigham and Women's Hospital 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 25 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 28 Jul 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Chi-Joan How (617-732-5190, jhow@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients consented and enrolled within 2 years of study opening (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2026.