Clinical trial NCT06189508: A Study to Evaluate Single Subcutaneous Doses of NXT007 Among Injection Sites Abdomen, Upper Arm, and Thigh in Healthy Male Participants
Official title: An Open-Label, Parallel-Group Phase I Study to Evaluate the Relative and Absolute Bioavailability of Single Subcutaneous Doses of NXT007 Among Injection Sites Abdomen, Upper Arm, and Thigh in Healthy Male Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male Participants
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2024-01-03
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase I, open-label, non-randomized, parallel-group, single-dose study in healthy adult male participants. The aim is to investigate the relative bioavailability (rBA) of NXT007 among subcutaneous (SC) injection sites (abdomen, upper arm, and thigh) and the absolute bioavailability (aBA) of SC NXT007 administration. In addition, the pharmacodynamic, safety, tolerability, and immunogenicity of a single dose of NXT007 following SC or intravenous (IV) administration are assessed.


Eligibility criteria: Inclusion Criteria:

* Overtly healthy as determined by medical evaluation that includes medical history, physical examination, vital signs, laboratory tests, and 12-lead ECG
* Body mass index (BMI) within the range of 18.5 to 30.0 kg/m\^2
* Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm

Exclusion Criteria:

* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data
* History of allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies; or known hypersensitivity to any constituent of the product
* Clinically relevant medical history and/or family history or signs of thromboembolic disease such as deep vein thrombosis
* FVIII activity ≥120 International Units per decilitre (IU/dL) at screening
* Clinically significant abnormality on electrocardiogram (ECG) at screening such as QTcF after 10-minute supine rest \>450 milliseconds (ms); marked resting bradycardia (mean heart rate \<40 beats per minute \[bpm\]); marked resting tachycardia (mean heart rate \>100 bpm); or any other clinically significant ECG abnormality
* Supine systolic blood pressure at screening ≥140 millimetres of mercury (mm Hg) or \<90 mm Hg or supine diastolic blood pressure at screening ≥90 mm Hg or \<40 mm Hg
* Clinically significant abnormality on protein C activity (chromogenic assay), activated protein C resistance test, protein S free antigen, and/or antithrombin III activity levels
* Poor peripheral venous access
* Any other reason that, in the judgment of the investigator, would render the participants unsuitable for study participation

Primary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of NXT007
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Maximum Observed Plasma Concentration (Cmax) of NXT007
timeFrame: At prespecified timepoints from Day 1 until Day 253
Secondary outcomes:
measure: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUC0-last) of NXT007
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Time to Maximum Observed Plasma Concentration (tmax) of NXT007
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Apparent Terminal Half-Life (t1/2) of NXT007
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Apparent Clearance (CL/F) of NXT007 SC Administration
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Total Body Clearance (CL) of NXT007 IV Administration
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Volume of Distribution at Steady State of NXT007 IV Administration
timeFrame: At prespecified timepoints from Day 1 until Day 253
measure: Incidence and Severity of Adverse Events
timeFrame: From the single dose of study treatment (Day 1) until study completion (Day 253)
measure: Number of Participants with Abnormal Laboratory Values in Clinical Chemistry Parameters
timeFrame: From the single dose of study treatment (Day 1) until study completion (Day 253)
measure: Number of Participants with Abnormal Laboratory Values in Hematology Parameters
timeFrame: From the single dose of study treatment (Day 1) until study completion (Day 253)
measure: Change from Baseline in Pulse Rate at Specified Timepoints
timeFrame: Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253
measure: Change from Baseline in Tympanic Temperature at Specified Timepoints
timeFrame: Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253
measure: Change from Baseline in Systolic Blood Pressure at Specified Timepoints
timeFrame: Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253
measure: Change from Baseline in Diastolic Blood Pressure at Specified Timepoints
timeFrame: Baseline, Days 1, 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253
measure: Change from Baseline in Heart Rate at Specified Timepoints, as Measured by Electrocardiogram
timeFrame: Baseline, Days 1, 2, 8, 22, 43, 71, 141, and 253
measure: Change from Baseline in RR, PR, QRS, QT, and QTcF Intervals at Specified Timepoints, as Measured by Electrocardiogram
timeFrame: Baseline, Days 1, 2, 8, 22, 43, 71, 141, and 253
measure: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) at Specified Timepoints
timeFrame: Baseline, Days 1, 2, 8, 15, 18, 20, 22, 29, 43, 57, 71, 85, 113, 141, 169, 197, 225, and 253
measure: Change from Baseline in the Maximum Concentration of Thrombin Generated at Specified Timepoints
timeFrame: Baseline, Days 1, 18, 20, and 22
measure: Prevalence of Anti-Drug Antibodies (ADAs) to NXT007 at Baseline and Incidence of ADAs to NXT007 During the Study
timeFrame: From Baseline until Day 253
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research - Auckland
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: