A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Characteristics of DISC-3405 in Adult Healthy Male and Female Volunteers
Overview
- Phase
- Phase 1
- Intervention
- DISC-3405
- Conditions
- Healthy Volunteer
- Sponsor
- Disc Medicine, Inc
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This phase 1 study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of DISC-3405 in adult male and female healthy volunteers.
Detailed Description
Each enrolled subject will receive one single or multiple doses of DISC-3405 or placebo. During the study, subjects will be evaluated for safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of DISC-3405. In the single ascending dose (SAD) phase, a sentinel group of two subjects will be dosed first: one with DISC-3405, and the other with placebo; the randomization and blinding will be maintained. The remaining subjects for the cohort will be dosed at least 24 hours after the last sentinel dosing following approval from the principal investigator. Subsequent multiple ascending dose (MAD) cohorts will only enroll after a sufficient safety observation period for the SAD cohort, accordingly there will be no sentinel participants for cohorts in MAD. DISC-3405 or placebo will be administered as an IV infusion or subcutaneous injection. Subjects will have end-of-study (EOS) follow-up visits on Day 99 after the last administration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and female subjects, non-smokers, ages 18-65 (inclusive) at the time of signing the informed consent
- •No clinically significant medical history and in good health as determined by detailed medical history
- •Body mass index (BMI) 18.0 - 33.0 kg/m2 (inclusive) and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females
Exclusion Criteria
- •History of severe infection within 4 weeks prior to administration; signs and symptoms of any active infection regardless of severity within 2 weeks prior to administration.
- •History of hypersensitivity to similar drugs to DISC-3405 or their excipients.
- •Use of any prescription drugs, herbal supplements, or nonprescription drugs, including oral anti-histamines (for seasonal allergies), within 1 month or 5 half-lives (whichever is longer) prior to study drug administration, or dietary supplements within 1 week prior to study drug administration, unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with the study. Over-the-counter multivitamins will not be permitted. If needed, paracetamol/acetaminophen (up to 2 grams daily) may be used but must be documented in the Concomitant medications/Significant non-drug therapies page of the source data. Any questions of concomitant medications should be directed to the Sponsor.
- •Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
- •Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing
- •Pregnant, or nursing females.
- •A history of clinically significant psychiatric and psychological condition that, in the judgment of the investigator, may interfere with the planned treatment and follow-up, affect subject compliance, or place the subject at high risk from treatment-related complications
- •Abnormal and clinically significant ECG (QT-interval corrected according to Fridericia's formula \[QTcF\] \> 450 msec).
- •Clinically significant abnormal vital signs at screening (systolic blood pressure \[SBP\] \<90 mmHg or ≥140 mmHg; diastolic blood pressure \[DBP\] \<50 mmHg or ≥90 mmHg; heart rate \<50 beats per minute \[bpm\] or \>100 bpm).
- •Clinically significant abnormal laboratory test results or positive serology test results for hepatitis b surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen and antibody at screening.
Arms & Interventions
Single Ascending Dose of DISC-3405
Intervention: DISC-3405
Single Ascending Dose of Placebo
Intervention: Placebo
Multiple Ascending Dose of DISC-3405
Intervention: DISC-3405
Multiple Ascending Dose of Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of adverse events
Time Frame: up to 99 days
Incidence of treatment-emergent clinically abnormal physical exam
Time Frame: up to 99 days
Incidence of treatment-emergent clinically significant electrocardiograms (ECGs)
Time Frame: up to 99 days
Incidence of treatment-emergent clinically abnormal vital signs
Time Frame: up to 99 days
Incidence of treatment-emergent clinically significant laboratory test results
Time Frame: up to 99 days
Secondary Outcomes
- Plasma maximum measured drug concentration (Cmax)(up to 99 days)
- Area under the concentration-time curve from dosing to the last measurable time point (AUC0-t)(up to 99 days)
- Time of maximum concentration (Tmax)(up to 99 days)
- Drug elimination half-life (T½ el)(up to 99 days)
- Change from baseline in transferrin saturation (TSAT) levels(up to 99 days)
- Area under the concentration-time curve from dosing to infinity (AUC0-∞)(up to 99 days)
- Volume of plasma cleared (CL)(up to 99 days)
- Trough Concentration (Ctrough)(up to 99 days)
- Volume of Distribution (Vd)(up to 99 days)
- Change from baseline of hepcidin levels(up to 99 days)
- Elimination rate constant (Kel)(up to 99 days)
- Change from baseline of serum iron levels(up to 99 days)