A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)

NCT07187973 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DISC-3405-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

This is an open-label, multicenter, within-participant dose-escalation study examining up to 3 dose levels of DISC-3405 and will assess the safety, tolerability, PK, and PD of DISC 3405 in participants with sickle cell disease.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of DISC-3405 administration in participants with SCD

  Proportion of participants with treatment-emergent adverse events (TEAEs), changes in vital signs, changes in physical examinations, changes in electrocardiograms (ECGs), and changes in clinical laboratory results

  Up to 36 weeks

Secondary Outcomes (14)

• Pharmacodynamic (PD) properties of DISC-3405 in participants with SCD by change from baseline for hemoglobin (Hgb)

  Up to 36 weeks

• Pharmacodynamic (PD) properties of DISC-3405 in participants with SCD by change from baseline for hematocrit (HCT)

  Up to 36 weeks

• Pharmacodynamic (PD) properties of DISC-3405 in participants with SCD by change from baseline for reticulocyte count

  Up to 36 weeks

• Pharmacodynamic (PD) properties of DISC-3405 in participants with SCD by change from baseline for Red Blood Cell Count (RBC)

  Up to 36 weeks

• Pharmacodynamic (PD) properties of DISC-3405 in participants with SCD by change from baseline for Lactate Dehydrogenase (LDH)

  Up to 36 weeks

Study Arms (1)

Within-participant dose escalation

EXPERIMENTAL

This is an open-label, multicenter, within-participant dose-escalation study examining up to 3 dose levels of DISC-3405.

Drug: DISC-3405

Interventions

DISC-3405 DRUG

DISC-3405 is administered subcutaneously.

Within-participant dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older at the time of signing the informed consent form (ICF).
• Male or female study participants with SCD HbSC or HbSS.
• Participants who have been diagnosed with any of the following SCD-related complications: between 1-10 episodes of VOC in the past 12 months, any history of sickle cell related retinopathy, silent cerebral infarct, avascular necrosis, sensorineural hearing loss; or at least 1 episode of priapism, hepatic sequestration, splenic sequestration, or splenic infarct within the last 12 months as assessed locally.
• Hgb ≥7.0 g/dL during Screening. The first 2 participants must have an Hgb ≥9 g/dL.
• Normal alpha globin gene screen.
• Absolute reticulocyte count or % reticulocyte count \>1.5 × upper limit of normal (ULN) during Screening.
• TSAT ≥15% at Screening.
• Ferritin ≥50 ng/mL for HbSC or ≥100 ng/mL for HbSS (ferritin must be \<1000 ng/mL at Screening).
• For participants taking hydroxyurea, L-glutamine, or crizanlizumab, stable dose for at least 2 months prior to Screening and with no anticipated need for dose adjustments during the study.
• If male, not vasectomized for at least 6 months, with female sexual partner(s) of childbearing potential, agrees he and partner will use double methods of the following highly effective methods of birth control (described below) from the first dose of randomized study drug until 120 days after the last administration of study drug and must not donate sperm during their study participation:
• Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Intrauterine device, in place for at least 3 months (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• If female, then EITHER postmenopausal, defined as at least 12 months natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agree to use 1 of the following highly effective methods of birth control on Day 1 (or earlier) and for at least 120 days after the last administration of study drug:
• Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).

You may not qualify if:

• Participants who are receiving regularly scheduled blood (RBC) transfusion therapy or phlebotomy or have received RBC transfusion or phlebotomy within 60 days of Screening.
• Hospitalized for VOC or other sickle cell related complication within 14 days of Screening.
• Participants with clinically significant bacterial, fungal, parasitic, or viral infection.
• Active HIV, hepatitis B, or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment.
• Significant renal dysfunction, evidenced by estimated glomerular filtration rate of \<60 mL/min/1.73 m2 at the Screening visit, as assessed locally.
• Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>2.5 × ULN.
• Any episode of ACS in the last 6 months.
• Prior or planned hematopoietic stem cell transplant or gene therapy.
• History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening.
• 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.
• Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
• A history or known allergic reaction to any IP excipients or history of anaphylaxis to any food or drug.
• History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
• 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 an unacceptable risk or otherwise preclude the participant from participating in the study.
• Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.

Sponsors & Collaborators

• Disc Medicine, Inc: lead

Study Sites (4)

Julie Kanter

Birmingham, Alabama, 35294, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Innovative Hematology - Indiana Hemophilia & Thrombosis Center

Indianapolis, Indiana, 46260, United States

RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Disc Medicine Clinical Trials

CONTACT

(617) 674 9274; clinicaltrials@discmedicine.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Up to 2 cohorts of participants are planned: * Cohort A will enroll 12 participants with HbSC or HbSS. At least one-third of participants must be HbSC, and at least one-third of participants must be HbSS. * Cohort B is optional and will enroll up to 12 participants with HbSC or HbSS, administering previously studied or lesser dose levels and regimens

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 23, 2025
• Study Start: January 6, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 6, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)