Healthy Adult Participants, Hemophilia A
Conditions
Keywords
ARD001, Single Ascending Dose, Healthy Volunteers, Hemophilia A, Coagulation
Brief summary
This study is evaluating ARD001, an investigational medicine being developed for the treatment of hemophilia A. In Phase 1, healthy adult participants will receive a single dose of ARD001 or placebo to assess its safety and tolerability, how it moves through the body, its effects on blood coagulation, and whether the body develops antibodies against it. If the Phase 1 results support further study and the required regulatory and ethics approvals are obtained, Phase 2 will evaluate repeated doses of ARD001 in adults with hemophilia A. Phase 2 is not currently open for enrollment. The study is designed to determine whether ARD001 can be administered with acceptable safety and to identify doses suitable for further clinical development.
Interventions
BIOLOGICALARD001
ARD001 will be administered subcutaneously as a single dose of 0.01, 0.1, or 0.3 mg/kg in Phase 1. A multiple-dose regimen is planned for Phase 2 and will be specified in a protocol amendment before Phase 2 initiation
OTHERPlacebo
The corresponding placebo will be administered subcutaneously as a single dose in Phase 1
Sponsors
Arditus Pte Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Phase 1 is blinded to participants, investigators and designated clinical care personnel. Designated unblinded pharmacy personnel will prepare and dispense study treatment. Phase 2 is planned to be open-label.
Intervention model description
Phase 1 comprises three sequentially single-ascending dose cohorts in healthy adults, with participants randomized within each cohort to ARD001 or Placebo. Phase 2 is planned as an open-label, multiple-dose study in adults with Hemophilia A and will be further defined in a protocol amendment before initiation.
Eligibility
Sex/Gender
MALE
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Phase 1 Inclusion Criteria: * Healthy adults within the specified age and body-weight ranges * Able and willing to provide informed consent * Considered healthy based on medical history, physical examination, vital signs, electrocardiogram and laboratory assessments * Other essential criteria from the approved protocol Phase 1
Exclusion criteria
* History of severe drug or food allergy, or known allergy to ARD001 or its components * Acute infection within 14 days before dosing or fever on the planned dosing day * Clinically significant cardiovascular, coagulation, hepatic, renal or other medical abnormality * Recent use of prohibited medications within the protocol-defined washout periods * Other major exclusions from the approved protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest | From first dose through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Number and percentage of participants with treatment-emergent adverse events, serious adverse events, and adverse events of special interest will be summarised. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Anti-Drug Antibodies to ARD001 | From baseline through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Number and percentage of participants with treatment-induced or treatment-boosted binding anti-drug antibodies to ARD001. |
| Time to First Detection of Anti-Drug Antibodies to ARD001 | From first dose through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Time from first dose to the first scheduled post-baseline sample with a positive binding anti-drug antibody result. |
| Anti-Drug Antibody Titre to ARD001 | From baseline through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Binding anti-drug antibody titre in participants with a positive anti-drug antibody result. |
| Persistence of Anti-Drug Antibodies to ARD001 | From baseline through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Persistence of binding anti-drug antibodies to ARD001 based on positive results at protocol-specified post-dose assessment time points. |
| Observed Body Weight and Change From Baseline | Baseline and protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed body weight values and changes from baseline will be summarized. |
| Number of Participants With Clinically Significant Changes From Baseline in Hematology Parameters | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Hematology assessments include white blood cell count with differential (neutrophils, lymphocytes, monocytes, eosinophils and basophils), red blood cell count and indices (mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration), hemoglobin, and platelet count. The number of participants with clinically significant changes from baseline in hematology parameters will be summarized. Clinical significance will be determined by the investigator. |
| Apparent Volume of Distribution During the Terminal Phase of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Apparent volume of distribution during the terminal phase following subcutaneous administration (Vz/F) of ARD001 derived using noncompartmental analysis. |
| Apparent Clearance of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Apparent clearance following subcutaneous administration (CL/F) of ARD001 derived using noncompartmental analysis. |
| Number of Participants With Clinically Significant Changes From Baseline in Serum Chemistry Parameters | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Serum chemistry assessments include creatinine, blood urea nitrogen, sodium, potassium, magnesium, phosphate, calcium, chloride, bicarbonate, fasting blood glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total and direct bilirubin, thyroid-stimulating hormone, free thyroxine, lactate dehydrogenase, creatine kinase, C-reactive protein, and uric acid. The number of participants with clinically significant changes from baseline in serum chemistry parameters will be summarized. Clinical significance will be determined by the investigator. |
| Number of Participants With Clinically Significant Changes From Baseline in Urinalysis Parameters | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Urinalysis assessments include dipstick measurements of pH, protein, glucose, ketone, and blood, with reflex comprehensive urinalysis if abnormal as specified in the protocol. The number of participants with clinically significant changes from baseline in urinalysis parameters will be summarized. Clinical significance will be determined by the investigator. |
| Number of Participants With Clinically Significant Changes From Baseline in Coagulation Parameters | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Coagulation assessments include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and thrombin time. The number of participants with clinically significant changes from baseline in coagulation parameters will be summarized. Clinical significance will be determined by the investigator. |
| Observed Values and Change From Baseline in Systolic Blood Pressure | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed systolic blood pressure values and changes from baseline will be summarised. |
| Observed Values and Change From Baseline in Diastolic Blood Pressure | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | — |
| Observed Values and Change From Baseline in Pulse Rate | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | — |
| Observed Values and Change From Baseline in Respiratory Rate | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | — |
| Observed Values and Change From Baseline in Body Temperature | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | — |
| Observed Values and Change From Baseline in PR Interval | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed PR interval values and changes from baseline obtained from protocol-specified 12-lead electrocardiograms will be summarised. |
| Observed Values and Change From Baseline in QRS Duration | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed QRS duration values and changes from baseline obtained from protocol-specified 12-lead electrocardiograms will be summarised. |
| Observed Values and Change From Baseline in QT Interval | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed uncorrected QT interval values and changes from baseline obtained from protocol-specified 12-lead electrocardiograms will be summarised. |
| Observed Values and Change From Baseline in QTcF Interval | At baseline and at protocol-specified post-dose assessment time points through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Observed QT interval values corrected using Fridericia's formula and changes from baseline obtained from protocol-specified 12-lead electrocardiograms will be summarised. |
| Maximum Observed Serum Concentration of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Maximum observed serum concentration (Cmax) of ARD001 derived using noncompartmental analysis. |
| Time to Maximum Observed Serum Concentration of ARD001 | Time of maximum observed serum concentration (Tmax) of ARD001 derived using noncompartmental analysis. | Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) of ARD001 derived using noncompartmental analysis. |
| Area Under the Serum Concentration-Time Curve Extrapolated to Infinity | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of ARD001 derived using noncompartmental analysis. |
| Mean Residence Time From Time Zero to Infinity of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Mean residence time from time zero to infinity (MRT0-inf) of ARD001 derived using noncompartmental analysis. |
| Lag Time Before the First Measurable Serum Concentration of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Time before the first measurable non-zero serum concentration (Tlag) of ARD001 derived using noncompartmental analysis. |
| Terminal Elimination Rate Constant of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Apparent terminal elimination rate constant (λz) of ARD001 derived from the terminal portion of the serum concentration-time profile using noncompartmental analysis. |
| Area Under the Serum Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) of ARD001 derived using noncompartmental analysis. |
| Apparent Terminal Elimination Half-Life of ARD001 | From pre-dose through protocol-specified pharmacokinetic sampling through Day 29 for Cohort A1 and Day 113 for Cohorts A2 and A3. | Apparent terminal elimination half-life (t1/2) of ARD001 derived using noncompartmental analysis. |
Countries
Singapore
Outcome results
None listed