* Inclusion Criteria
1. Chinese male and female participants aged 18 years or older at the time of signing of informed consent.
2. Participant understands the trial procedures, is willing and able to adhere to trial requirements, and agrees to participate in the trial by providing written informed consent.
3. Meets the revised 2016 World Health Organization criteria for the diagnosis of polycythemia vera (PV).
4. Participant with inadequate hematocrit control who meets all of the following criteria:
1. Greater than or equal to (≥) 3 times documented hematocrit ≥45 percent (%) within 28 weeks prior to trial intervention or ≥5 times documented hematocrit ≥ 45% hematocrit within 1 year prior to trial intervention.
2. Documented hematocrit ≥45% within 3 months prior to trial intervention.
3. Phlebotomy or erythrocytapheresis, if performed, must not have occurred within 6 days of trial intervention administration (the day of phlebotomy or erythrocytapheresis and the day of trial intervention administration should not be included in the 6-day count).
5. Complete blood count immediately prior to trial intervention administration must meet the following criteria:
1. Hematocrit less than (\<) 45%.
2. White blood cell count within the range of 4000/microliter (µL) to 20,000/µL (inclusive), and
3. Platelet count within the range of 100,000/µL to 1,000,000/µL (inclusive).
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
7. Participants receiving cytoreductive therapy (CRT) at the time of trial intervention administration must be on a stable PV treatment regimen, including:
1. Hydroxyurea: at least 8 weeks.
2. JAK inhibitor: at least 8 weeks.
3. Interferon: at least 24 weeks.
8. Women of childbearing potential (WOCBP) agrees to use at least 1 form of highly effective contraception during the trial and for 30 days after the last dose of trial intervention.
9. A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for a period of 30 days after receiving the last dose of trial medication.
10. A fertile male participant agrees to use a condom, preferably combined with at least 1 form of acceptable contraception for any WOCBP partner(s) during the trial and for 90 days after the last dose of trial intervention.
11. A male participant must agree not to donate sperm for the purpose of reproduction during the trial and for a minimum of 90 days after receiving the last dose of trial medication.
* Exclusion Criteria
1. Clinically significant laboratory abnormalities at screening, including but not limited to:
1. Estimated glomerular filtration rate (eGFR): \<15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 2021. Estimated Glomerular Filtration Rate (eGFR) =142 × (serum creatinine \[Scr\] / A)\^B × 0.9938\^age × (1.012 if female), where A and B are the following: Female: Scr less than equal to (≤) 0.7, A equals to (=) 0.7, B=-0.241; Scr greater than (\>) 0.7, A=0.7, B=-1.2. Male: Scr ≤0.9, A=0.9, B=-0.302; Scr \>0.9, A=0.9, B=-1.2. Creatinine unit conversion: milligrams per deciliter (mg/dL) =micromoles per liter (μmol/L)/88.4.
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5×upper limit of normal (ULN).
3. Total bilirubin \>1.5×ULN.
2. Those who require phlebotomy at hematocrit levels \<45%.
3. Clinically significant thrombosis (for example, deep vein thrombosis or splenic vein thrombosis) within 2 months prior to trial intervention.
4. Active or chronic bleeding within 2 months prior to trial intervention.
5. Those who meet the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment.
6. In situ or Stage 1 squamous cell carcinoma of the skin, in situ or Stage 1 basal cell carcinoma of the skin, or in situ melanoma of the skin, as determined by the dermatologic examination required at screening unless the cancer is adequately treated prior to trial intervention.
7. Any infection requiring systemic therapy within 1 month of dosing except controlled human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. Prophylactic therapies are allowed.
8. Any serious or unstable medical condition (for example, poorly controlled HIV infection) or uncontrolled psychiatric condition that, in the judgement of the investigator, would impair the participant's ability to participate in the trial.
9. Major surgical procedure within 2 months prior to trial intervention, unless the participant has fully recovered from the surgery; or planned major elective surgery during the trial.
10. History of invasive malignancies within the last 5 years, except
1. Localized cured cancer (for example, prostate cancer and cervical cancer).
2. Localized cured in situ or Stage 1 squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or in situ melanoma of the skin.
11. Pregnant females.
12. Those capable of breastfeeding but do not agree to forego breastfeeding from the first dose of trial intervention through 30 days after the last dose.
13. Active alcohol or drug addiction that would interfere with their ability to comply with trial requirements.
14. Those who do not complete at least 4 days of Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 assessments within 1 week prior to trial intervention.
15. Receipt of an investigational agent within 2 months or 5 half-lives, whichever is longer, prior to trial intervention.
16. Receipt of busulfan or \^ 32 phosphorus within 7 months prior to screening.
17. Known hypersensitivity to rusfertide or any of its excipients.
18. Any lesion or mass detected by physical examination or imaging during screening that is suspicious for malignancy, unless it has been evaluated and confirmed to be nonmalignant.
