Study to Evaluate the Safety, Tolerability, PK and PD of DISC-0974 in Healthy Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, PK and PD of DISC-0974 in Healthy Subjects Following Dose-Escalating Single Intravenous or Subcutaneous Administration

This Phase 1 study of DISC-0974 will assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of DISC-0974 in adult healthy volunteers.

Enrolled participants in this study will receive a single dose of DISC-0974 or a placebo. Samples will be collected to measure how DISC-0974 is processed by the body and how the body responds when exposed to DISC-0974. Participants will receive a single study drug dose on Day 1; and follow-up for 10 weeks (71 days). If an undetectable DISC-0974 blood concentration is observed, the duration of follow-up will be shortened to 7 days thereafter, as feasible.

Inclusion Criteria:

• Male or female (HV only) adults aged 18 to 65 years, inclusive at the time of consent.
• Body weight ≥50 kg and body mass index (BMI) between 18 and 33, inclusive, at Screening.
• Systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 at Screening.
• No clinically significant abnormalities as determined by medical history, by results of physical examination, vital signs, ECG and lab tests at Screening.
• QTcF <450 msec at Screening.
• Estimated glomerular filtration rate >60 mL/min/1.73m2 based on the 4 parameter MDRD (Modification of Diet in Renal Disease) equation at Screening
• TSAT ≤30% at Screening, as determined in a fasting morning blood sample (06:00 to 11:00 hours).
• Hematologic parameters (red blood cell count [RBC], hemoglobin, hematocrit, platelet count, mean corpuscular volume, mean corpuscular hemoglobin concentration), serum iron, and TIBC within normal range and serum ferritin (within normal range and ≥30 ng/mL) at Screening.
• If a male with female sexual partner(s) of childbearing potential, must agree to use acceptable methods of birth control during the study and through the End of Study (EOS) visit
• If female, postmenopausal, as defined with at least 12 months natural, spontaneous amenorrhea, or at least 6 weeks following surgical menopause
• Able to understand and provide written informed consent and comply with protocol requirements

Exclusion Criteria:

• History of anemia or hematologic disorder within 1 year of Screening
• History of splenectomy
• Diagnosis or first-degree relative with a diagnosis of hemochromatosis
• History of diabetes, cardiovascular, hepatic, renal, or malabsorptive disease
• Vegan or iron-deficient diet within 3 months of Screening
• Blood transfusion within 1 year of Screening
• Whole blood donation within 6 months of Screening or plasma donation within 30 days of Screening.
• A history of alcohol or illicit drug use disorder within 3 years of Screening, as assessed by the Investigator
• Use of any tobacco- and/or nicotine-containing containing products, including e-cigarettes, vaping products, and nicotine replacement products, within 3 months of Screening
• Use of multivitamin or iron supplements within 30 days prior to Screening
• ALT or aspartate aminotransferase (AST) level above the normal range at Screening
• Positive urine pregnancy test at Screening or Baseline (Day -1).
• Positive serologic test for Hepatitis B surface antigen, Hepatitis C antibody, or human immunodeficiency virus (HIV) at Screening.
• Positive urine screen for drugs of abuse or alcohol test on admission to the study center
• Use of any systemic prescription medication within 14 days of Screening, non-iron containing dietary supplements, or non-prescription drugs within 7 days of dosing.
• History of a major surgical procedure within 60 days of Screening or planned surgical procedure within 90 days of dosing.
• A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug.
• History or presence or any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions.