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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: DISC-0974
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteer: Single Ascending Dose of DISC-0974<br>Single Intravenous (IV) or Subcutaneous (SC) ascending dose in healthy volunteers | Drug: DISC-0974<br>* DISC-0974 is administered (IV infusion or Subcutaneous Injection) as a single dose<br>|
| Experimental: Healthy Volunteer: Single Ascending Dose of Placebo<br>Single Intravenous (IV) or Subcutaneous (SC) ascending dose in healthy volunteers | Drug: Placebo<br>* Placebo is administered (IV infusion or Subcutaneous Injection) as a single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Up to 71 days of monitoring | 
| Incidence of abnormal laboratory test results |  | Up to 71 days of monitoring | 
| Incidence of treatment-emergent clinically abnormal electrocardiogram (ECG) |  | Up to 71 days of monitoring | 
| Incidence of treatment-emergent clinically abnormal physical exam |  | Up to 71 days of monitoring | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma maximum measured drug concentration (Cmax) |  | Up to 71 days of testing | 
| Time of maximum concentration (Tmax) |  | Up to 71 days of testing | 
| Area under the concentration-time curve (AUC) |  | Up to 71 days of testing | 
| Plasma half-life (T½) |  | Up to 71 days of testing |