Polycythemia Vera
Conditions
Keywords
Drug Therapy
Brief summary
Polycythemia vera (PV) is a long-term condition in which the bone marrow makes too many red blood cells (RBCs). Bone marrow is the soft tissue inside the large bones where blood cells are made. When there are too many RBCs, called erythrocytosis, the blood can become thicker and move less easily through blood vessels and organs. This can raise the risk of blood clots (thrombosis) in veins or arteries. Sometimes, these clots can be life-threatening and may cause a stroke or heart attack. Treatment aims to keep the percentage of RBCs in the blood (hematocrit) in a safe range. For adults with PV, this means keeping the hematocrit below 45%. This helps lower the blood thickness and the risk of thrombosis. PV can also be linked to low iron levels (iron deficiency), because the body uses iron to make more RBCs. Many people with PV are treated with blood removal (phlebotomy) to lower RBC levels in the blood. This can worsen the iron deficiency, because each blood removal also takes iron out of the body. Rusfertide is a medicine that lowers the amount of iron available in the blood. It works like hepcidin, a natural hormone that helps control iron levels in the body. By limiting iron available for RBC production, rusfertide may help keep hematocrit below 45% and may improve symptoms. It may also reduce, or even remove, the need for phlebotomy in people. The main aim of this study is to check how well rusfertide works to lower the number of phlebotomies needed in Chinese adults with PV. Other aims are to understand how well rusfertide works to keep hematocrit levels under control and how safe it is. The study also wants to learn how rusfertide moves through the body (pharmacokinetics) and if it causes the body's defense system to react to it (immunogenicity). During the study, participants will receive rusfertide for up to 1 year (52 weeks) and will have to visit their study clinic several times. Blood samples will be taken several times during the study.
Interventions
DRUGRusfertide
Rusfertide injections administered SC.
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Response Starting at Week 20 Through Week 32 | Week 20 through Week 32 | Response is defined as the absence of phlebotomy eligibility. Phlebotomy eligibility is defined as: A confirmed hematocrit ≥45%, which is ≥3% (absolute) higher than the baseline hematocrit or hematocrit ≥48%. Confirmation is defined as 2 consecutive hematocrit assessments that are ≥45% and at least 3% higher than the baseline hematocrit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hematocrit Over Time | From Baseline to Week 32 | — |
| Percentage of Participants Maintaining Hematocrit <45% During Week 0 to Week 32 and Week 0 to Week 52 | From Baseline to Weeks 32 and 52 | — |
| Median Time to First Hematocrit ≥45% After Enrollment | From Baseline to Week 52 | — |
| Percentage of Participants With at Least One Hematocrit ≥48% During Week 0 to Week 32 | From Baseline to Week 32 | — |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | From Baseline to Week 56 | An Adverse Event (AE) is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the trial intervention. A TEAE is defined as an AE that commences on or after the first dose of the trial intervention and within 4 weeks after the last dose of the trial intervention. |
| Percentage of Participants With Adverse Events of Special Interest (AESIs) | From Baseline to Week 56 | An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the trial intervention. AESIs for this trial include cancer events. |
| Plasma Concentration-Time Data for Rusfertide | From Baseline to Week 52 | — |
| Number of Participants With Anti-Rusfertide Antibodies | From Baseline to Week 56 | — |
Contacts
CONTACTTakeda Contact
STUDY_DIRECTORStudy Director
Takeda
Outcome results
None listed