A Study of DISC-3405 in Healthy Volunteers

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: DISC-3405
* Drug: DISC-3405
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. Immunization with a live or attenuated vaccine is prohibited within 4 weeks prior to study drug administration. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) or live attenuated vaccines and are not allowed. Receipt of an immunoglobulin or blood product 90 days prior to dosing History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit [more than 7 units for women or 14 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%)] or taking a product containing alcohol 2 days prior to dosing, or positive alcohol breath test at screening. History of significant drug abuse within one year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs [such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and amphetamine derivatives] within 1 year prior to screening. Positive urine drug screen, including a cotinine test at screening and on Day -1. Active infection with COVID-19. Subjects who have quarantined and are no longer deemed infectious may enroll. Subjects who received a COVID-19 vaccine within 4 weeks prior to dosing, or plan to receive COVID-19 vaccine during the time of their study participation

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose of DISC-3405<br> | Drug: DISC-3405<br>* DISC-3405 is administered as a single dose IV infusion or subcutaneous injection<br>* Other names: 9MW3011;|
| Placebo Comparator: Single Ascending Dose of Placebo<br> | Drug: Placebo<br>* Placebo is administered as a single dose IV infusion or subcutaneous injection<br>|
| Experimental: Multiple Ascending Dose of DISC-3405<br> | Drug: DISC-3405<br>* DISC-3405 is administered in multiple ascending doses as an IV infusion or subcutaneous injection<br>* Other names: 9MW3011;|
| Placebo Comparator: Multiple Ascending Dose of Placebo<br> | Drug: Placebo<br>* Placebo is administered in multiple ascending doses as an IV infusion or subcutaneous injection<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 99 days | 
| Incidence of treatment-emergent clinically abnormal physical exam |  | up to 99 days | 
| Incidence of treatment-emergent clinically significant laboratory test results |  | up to 99 days | 
| Incidence of treatment-emergent clinically significant electrocardiograms (ECGs) |  | up to 99 days | 
| Incidence of treatment-emergent clinically abnormal vital signs |  | up to 99 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma maximum measured drug concentration (Cmax) |  | up to 99 days | 
| Time of maximum concentration (Tmax) |  | up to 99 days | 
| Area under the concentration-time curve from dosing to the last measurable time point (AUC0-t) |  | up to 99 days | 
| Area under the concentration-time curve from dosing to infinity (AUC0-∞) |  | up to 99 days | 
| Drug elimination half-life (T½ el) |  | 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 | 
| Elimination rate constant (Kel) |  | up to 99 days | 
| Change from baseline of hepcidin levels |  | up to 99 days | 
| Change from baseline in transferrin saturation (TSAT) levels |  | up to 99 days | 
| Change from baseline of serum iron levels |  | up to 99 days |