Clinical trial NCT06985147: A Phase 2, Open-Label Study of DISC-3405 in Participants With Polycythemia Vera (PV)
Official title: A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DISC-3405 in Participants With Polycythemia Vera (PV)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Polycythemia Vera (PV)
Lead sponsor: Disc Medicine, Inc
Sponsor class: INDUSTRY
First posted: 2025-05-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Up to 2 cohorts of participants are planned:

* Cohort A will first enroll 4 participants who 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 8 participants will be enrolled and administered a starting dose level of Dose B DISC-3405 subcutaneous.
* Cohort B is optional and will enroll 8 participants administered a dose level up to that previously studied.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 prior to Day 1 of HCT \<45% or HCT \<48% if followed by a phlebotomy within 2 weeks prior to baseline, 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 study treatment or at least 5 phlebotomies in 52 weeks before study treatment. 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-alpha 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 and serum follicle-stimulating hormone \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy or hysterectomy); OR agreeable to use of highly effective contraception (listed below) on Day 1 (or earlier) 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 of Screening.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE
timeFrame: Up to 365 days
measure: Incidence of clinically abnormal vital signs
timeFrame: Up to 365 days
measure: Incidence of clinically abnormal physical exam
timeFrame: Up to 365 days
measure: Incidence of clinically abnormal electrocardiograms
timeFrame: Up to 365 days
measure: Incidence of abnormal laboratory test results
timeFrame: Up to 365 days
Secondary outcomes:
measure: Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the maintenance period
timeFrame: Up to 365 days
measure: Number of phlebotomies during the maintenance and optimization periods
timeFrame: Up to 365 days
measure: Proportion of participants achieving therapeutic response, defined as absence of phlebotomy eligibility, during the optimization period
timeFrame: Up to 365 days
measure: Proportion of participants with HCT values <45% throughout the study
timeFrame: Up to 365 days
measure: Area under the plasma concentration versus time curve (AUC) following the first dose
timeFrame: Up to 365 days
measure: Peak plasma concentration (Cmax) following the first dose
timeFrame: Up to 365 days
measure: Elimination half-life (t½el) following the first dose
timeFrame: Up to 365 days
measure: Apparent clearance (CL/F) following the first dose
timeFrame: Up to 365 days
measure: Maximum concentration at steady state (Cmax_ss) after repeating doses
timeFrame: Up to 365 days
measure: Pre-dose trough concentration (Ctrough) after repeating doses
timeFrame: Up to 365 days
measure: Change from baseline for HCT
timeFrame: Up to 365 days
measure: Change from baseline for serum hepcidin-25
timeFrame: Up to 365 days
measure: Change from baseline for serum iron
timeFrame: Up to 365 days
Other outcomes:
Locations:
Study officials:
affiliation: Disc Medicine
name: Will Savage, MD PhD
role: STUDY_DIRECTOR
References: