Respiratory Disease
Conditions
Brief summary
This goal of the open-label single dose study is to evaluate and compare the safety, tolerability, pharmacokinetic (PK), and immunogenicity of AIO-001 using two different formulations in 16 healthy volunteers.
Detailed description
This is an open-label single dose, parallel group, 24-week, Phase 1 study in 16 healthy participants. The study is designed to evaluate and compare the safety, tolerability, PK, and immunogenicity of AIO-001 using two different formulations (Formulation A and Formulation B) in 16 healthy volunteers (8 receiving each formulation). The study will include a screening visit from Day -28 to Day -2. Eligible participants will be admitted to the clinical site on Day -1 and will be confined until completion of the assessments on Day 3. Participants will return to the clinical site for outpatient visits for study assessments and laboratory tests.
Interventions
DRUGAIO-001
AIO-001 Solution for SC injection.
Sponsors
Aiolos Bio, Inc., a GSK Company
Syneos Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Able to understand the study procedures and provide signed informed consent to participate in the study. 2. Male or female. 3. Non-smokers. Light smokers (no more than 5 cigarettes daily \[approximately 50 to 60 mg of nicotine per day\], or products with equivalent amount of nicotine within 3 months prior to screening) may be permitted. 4. ≥18 and ≤55 years of age. 5. BMI \>18.5 and \<32.0 kg/m2 and body weight ≥45.0 kg. 6. Healthy participants.
Exclusion criteria
1. Any clinically significant abnormal finding at physical examination at screening. 2. 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, or QuantiFERON®-TB tuberculosis (TB) test at screening. 3. Positive pregnancy test or lactating female participant. 4. Positive urine drug screen or alcohol breath test. 5. History of anaphylaxis, or severe allergy. 6. Previous exposure to thymic stromal lymphopoietin antibody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From Day 1 up to Day 169 | An AE was defined as any untoward medical occurrence in a participant or clinical trial participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs were defined as AEs that commence on or after the time of study drug administration. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Baseline (Day -1) up to Day 169 | Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature measurements. The clinically significant changes were based on investigator's judgement. |
| Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram Parameters | Baseline (Day -1) up to Day 169 | The electrocardiogram parameters included heart rate, PR interval, QT interval, corrected QT (QTcF using Fridericia's formula) interval and QRS. The clinically significant changes were based on investigator's judgement. |
| Number of Participants With Clinically Significant Changes in Physical Examination Findings | Baseline (Day -1) up to Day 169 | Physical examination included assessments of the following: head, eyes, ears, nose, throat, neck, chest, lungs, abdomen, musculoskeletal, dermatological, cardiovascular/peripheral vascular, and general neurological examination. The clinically significant changes were based on investigator's judgement. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | Baseline (Day -1) up to Day 169 | Clinical laboratory parameters included biochemistry, hematology, and urinalysis assessment. The clinically significant changes were based on investigator's judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC0-last) of AIO-001 | Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. |
| Number of Participants With Positive Anti-drug Antibody (ADA) to AIO-001 | Up to Day 169 | ADA-positive participant was defined as participant with at least one treatment-induced or treatment-boosted ADA-positive sample at any time during the treatment or follow-up observation period. Anti-AIO-001 antibodies were evaluated in serum samples. Serum samples were screened for antibodies binding to AIO-001. |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of AIO-001 | Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose | Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. The residual area was greater than 20% in 15 out of the total of 16 participants and therefore the estimation of AUC0-inf may be non-identifiable. |
| Maximal Observed Concentration (Cmax) of AIO-001 | Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose | Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. |
| Time to Maximal Observed Concentration (Tmax) of AIO-001 | Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose | Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. |
| Terminal Elimination Half-life (T½) of AIO-001 | Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose | Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. The residual area was greater than 20% in 15 out of the total of 16 participants and therefore the estimation of T½ may be non-identifiable. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AIO-001: Formulation A Participants received 400 mg of 100 mg/ml AIO-001, administered as 4\*1.0 ml SC injection on Day 1. | 8 |
| AIO-001: Formulation B Participants received 400 mg of 182 mg/ml AIO-001, administered as 2\*1.1 ml SC injection on Day 1. | 8 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | AIO-001: Formulation B | Total | AIO-001: Formulation A |
|---|---|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 10.48 | 33.1 years STANDARD_DEVIATION 8.79 | 33.5 years STANDARD_DEVIATION 7.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 14 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 8 | 6 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram Parameters
The electrocardiogram parameters included heart rate, PR interval, QT interval, corrected QT (QTcF using Fridericia's formula) interval and QRS. The clinically significant changes were based on investigator's judgement.
Time frame: Baseline (Day -1) up to Day 169
Population: The safety population included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram Parameters | 0 Participants |
| AIO-001: Formulation B | Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters
Clinical laboratory parameters included biochemistry, hematology, and urinalysis assessment. The clinically significant changes were based on investigator's judgement.
Time frame: Baseline (Day -1) up to Day 169
Population: The safety population included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| AIO-001: Formulation B | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Physical Examination Findings
Physical examination included assessments of the following: head, eyes, ears, nose, throat, neck, chest, lungs, abdomen, musculoskeletal, dermatological, cardiovascular/peripheral vascular, and general neurological examination. The clinically significant changes were based on investigator's judgement.
Time frame: Baseline (Day -1) up to Day 169
Population: The safety population included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Clinically Significant Changes in Physical Examination Findings | 0 Participants |
| AIO-001: Formulation B | Number of Participants With Clinically Significant Changes in Physical Examination Findings | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature measurements. The clinically significant changes were based on investigator's judgement.
Time frame: Baseline (Day -1) up to Day 169
Population: The safety population included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| AIO-001: Formulation B | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a participant or clinical trial participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs were defined as AEs that commence on or after the time of study drug administration.
Time frame: From Day 1 up to Day 169
Population: The safety population included all participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| AIO-001: Formulation B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of AIO-001
Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. The residual area was greater than 20% in 15 out of the total of 16 participants and therefore the estimation of AUC0-inf may be non-identifiable.
Time frame: Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose
Population: The PK population included all participants who had at least 1 measured PK concentration following dosing. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AIO-001: Formulation A | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of AIO-001 | 7092.12 day*mcg/mL | Geometric Coefficient of Variation 30.49 |
| AIO-001: Formulation B | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of AIO-001 | 8088.05 day*mcg/mL | Geometric Coefficient of Variation 22.92 |
Secondary
Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC0-last) of AIO-001
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose
Population: The PK population included all participants who had at least 1 measured PK concentration following dosing. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AIO-001: Formulation A | Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC0-last) of AIO-001 | 4608.31 day*microgram per milliliter(day*mcg/mL) | Geometric Coefficient of Variation 30.04 |
| AIO-001: Formulation B | Area Under the Concentration-time Curve From Time Zero Until the Last Observed Concentration (AUC0-last) of AIO-001 | 4935.31 day*microgram per milliliter(day*mcg/mL) | Geometric Coefficient of Variation 18.18 |
Secondary
Maximal Observed Concentration (Cmax) of AIO-001
Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose
Population: The PK population included all participants who had at least 1 measured PK concentration following dosing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AIO-001: Formulation A | Maximal Observed Concentration (Cmax) of AIO-001 | 43.69 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 35.83 |
| AIO-001: Formulation B | Maximal Observed Concentration (Cmax) of AIO-001 | 47.49 micrograms per milliliter (mcg/mL) | Geometric Coefficient of Variation 22.22 |
Secondary
Number of Participants With Positive Anti-drug Antibody (ADA) to AIO-001
ADA-positive participant was defined as participant with at least one treatment-induced or treatment-boosted ADA-positive sample at any time during the treatment or follow-up observation period. Anti-AIO-001 antibodies were evaluated in serum samples. Serum samples were screened for antibodies binding to AIO-001.
Time frame: Up to Day 169
Population: The immunogenicity population included all participants who received any amount of AIO-001 and had at least one post-dose ADA measurement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AIO-001: Formulation A | Number of Participants With Positive Anti-drug Antibody (ADA) to AIO-001 | 0 Participants |
| AIO-001: Formulation B | Number of Participants With Positive Anti-drug Antibody (ADA) to AIO-001 | 4 Participants |
Secondary
Terminal Elimination Half-life (T½) of AIO-001
Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods. The residual area was greater than 20% in 15 out of the total of 16 participants and therefore the estimation of T½ may be non-identifiable.
Time frame: Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose
Population: The PK population included all participants who had at least 1 measured PK concentration following dosing. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AIO-001: Formulation A | Terminal Elimination Half-life (T½) of AIO-001 | 104.34 day | Standard Deviation 24.11 |
| AIO-001: Formulation B | Terminal Elimination Half-life (T½) of AIO-001 | 119.35 day | Standard Deviation 45.2 |
Secondary
Time to Maximal Observed Concentration (Tmax) of AIO-001
Blood samples were collected at indicated time points for PK analysis of AIO-001. PK analysis was conducted using standard non-compartmental methods.
Time frame: Pre-dose, 12, 24, 48, 72, 96, 120, 168, 240, 336, 504, 672, 1008, 1344, 1680, 2016, 2688, 3360, and 4056 hours post-dose
Population: The PK population included all participants who had at least 1 measured PK concentration following dosing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AIO-001: Formulation A | Time to Maximal Observed Concentration (Tmax) of AIO-001 | 13.55 day |
| AIO-001: Formulation B | Time to Maximal Observed Concentration (Tmax) of AIO-001 | 17.43 day |