Polycythemia Vera (PV)
Conditions
Brief summary
This open-label, multicenter, within-participant dose escalation study examining up to 2 dose levels of DISC-3405 will assess the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of DISC-3405 in participants with polycythemia vera (PV).
Interventions
DRUGDISC-3405
DISC-3405 is administered subcutaneously.
Sponsors
Disc Medicine, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Up to 3 cohorts of participants are planned: * Cohort A will include 20 participants. The first 4 participants enrolled will be administered a starting dose level of Dose A DISC-3405 subcutaneous which will be followed by within-participant dose escalation. Following Safety Review Committee review of the data, an additional 16 participants will be enrolled and administered a starting dose level of Dose B DISC-3405 subcutaneous. * Cohort B will enroll up to 20 participants administered a dose level of Dose B DISC-3405 subcutaneous once every 4 weeks. * Cohort C is optional and will enroll up to 20 participants administered a dose level up to that previously studied of DISC-3405 subcutaneous once every 4 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older at the time of signing the informed consent form (ICF). 2. Meet revised 2022 World Health Organization (WHO) criteria for the diagnosis of PV. 3. Complete blood count values at Screening of HCT \<45% or HCT \<48% if followed by a phlebotomy within 2 weeks, white blood cells 4000/μL to 20,000/μL (inclusive), and platelets 100,000/μL to 1,000,000/μL (inclusive). 4. At least 3 phlebotomies in 26 weeks before Screening or at least 5 phlebotomies in 52 weeks before Screening. At least 1 phlebotomy must be within the 12 weeks prior to Screening. 5. Participants receiving cytoreductive therapy must have been taking for at least 6 months and be on a stable PV therapy regimen for at least 2 months for hydroxyurea, interferon or ruxolitinib with no anticipated need for dose adjustments during the study, or have decreasing dose (with medical monitor approval). 6. Participants treated with phlebotomy alone must have stopped cytoreductive therapy 6 months before Screening. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, or with medical monitor approval, ECOG 2. 8. If male with female sexual partner(s) of childbearing potential, agrees to use one of the following acceptable methods of contraception during the study and for at least 120 days after the last study drug dose: 1. Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom or diaphragm \[female partner\]) 2. Intrauterine device in place for at least 3 months (female partner) 3. Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm) 4. Confirmed successful vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm) 9. If female, then EITHER postmenopausal, defined as at least 12 months of natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agreeable to use of highly effective contraception (listed below) on Day 1 (or earlier) and for at least 120 days after the last dose of study drug: 1. Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm) 2. Intrauterine device in place for at least 3 months 3. Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm) 10. Negative pregnancy test (females of childbearing potential). 11. Able to understand the study aims, procedures, and requirements, and provide written informed consent. 12. Able to comply with all study procedures.
Exclusion criteria
1. Clinically significant laboratory abnormalities at Screening. 2. Participants who require phlebotomy at HCT levels \<45%. 3. Clinically significant thrombosis (eg, deep vein thrombosis or splenic vein thrombosis) within 2 months prior to study treatment. 4. Clinically significant active or chronic bleeding, considered meaningful in consultation with the medical monitor, within 6 months prior to study treatment. 5. Significant renal dysfunction, evidenced by estimated glomerular filtration rate of \<30 mL/min/1.73 m2 at the Screening visit, as assessed locally. 6. History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable by the Sponsor. 7. Participants with 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 identified during Screening unless the cancer is adequately treated before study entry. 8. Received busulfan, pipobroman, or phosphorus-32 within 7 months prior to Screening. 9. Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery. 10. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug. 11. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator. 12. Active human immunodeficiency virus (HIV), hepatitis B or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment. 13. Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at unacceptable risk or otherwise preclude the participant from participating in the study. 14. Condition or concomitant medication that would confound the ability to interpret clinical data, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months. 15. If female, pregnant or breastfeeding. 16. Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days (or 5 half-lives for drugs, whichever is longer) of Screening. Previous use of other hepcidin inducing agents that may impact TMPRSS6 expression are not allowed. Previous use of hepcidin mimetics may be allowed in discussion with the Sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE | Up to 365 days | Proportion of participants with treatment-emergent adverse events |
| Incidence of clinically abnormal vital signs | Up to 365 days | Proportion of participants with changes in vital signs |
| Incidence of clinically abnormal physical exam | Up to 365 days | Proportion of participants with changes in physical examinations |
| Incidence of clinically abnormal electrocardiograms | Up to 365 days | Proportion of participants with changes in electrocardiograms (ECGs) |
| Incidence of abnormal laboratory test results | Up to 365 days | Proportion of participants with changes in clinical laboratory results |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the maintenance period | Up to 365 days |
| Number of phlebotomies during the maintenance and optimization periods | Up to 365 days |
| Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the optimization period | Up to 365 days |
| Proportion of participants with HCT values <45% throughout the study | Up to 365 days |
| Area under the plasma concentration versus time curve (AUC) following the first dose | Up to 365 days |
| Peak plasma concentration (Cmax) following the first dose | Up to 365 days |
| Elimination half-life (t½el) following the first dose | Up to 365 days |
| Apparent clearance (CL/F) following the first dose | Up to 365 days |
| Maximum concentration at steady state (Cmax_ss) after repeating doses | Up to 365 days |
| Pre-dose trough concentration (Ctrough) after repeating doses | Up to 365 days |
| Change from baseline for HCT | Up to 365 days |
| Change from baseline for serum hepcidin-25 | Up to 365 days |
| Change from baseline for serum iron | Up to 365 days |
| Apparent volume of distribution (Vd/F) | Up to 365 days |
Countries
United States
Contacts
STUDY_DIRECTORWill Savage, MD PhD
Disc Medicine
Outcome results
None listed