Clinical trial NCT04999527: Study to Evaluate the Safety, Tolerability, PK and PD of DISC-0974 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Disc Medicine, Inc
Sponsor class: INDUSTRY
First posted: 2021-08-11
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 71 days of monitoring
measure: Incidence of abnormal laboratory test results
timeFrame: Up to 71 days of monitoring
measure: Incidence of treatment-emergent clinically abnormal electrocardiogram (ECG)
timeFrame: Up to 71 days of monitoring
measure: Incidence of treatment-emergent clinically abnormal physical exam
timeFrame: Up to 71 days of monitoring
Secondary outcomes:
measure: Plasma maximum measured drug concentration (Cmax)
timeFrame: Up to 71 days of testing
measure: Time of maximum concentration (Tmax)
timeFrame: Up to 71 days of testing
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to 71 days of testing
measure: Plasma half-life (T½)
timeFrame: Up to 71 days of testing
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
affiliation: Disc Medicine
name: William Savage, MD, PhD
role: STUDY_DIRECTOR
References: