Atopic Dermatitis
Conditions
Brief summary
The study is a multicenter clinical trial and is designed as a proof-of-concept study to evaluate the efficacy, safety, tolerability, PK, immunogenicity, and PD of BSI-045B following SC injections. The study will enroll patients with moderate to severe AD to receive the 300 mg treatment. BSI-045B wil be firstly given weekly during Week 1 to Week 4, and then every 2 weeks (Q2W) to Week 24.
Detailed description
This study is a Phase 2a, proof-of-concept clinical study designed to evaluate the efficacy, safety, tolerability, PK, immunogenicity, and PD of BSI-045B injection in patients with moderate to severe AD. The study will be unblinded. Following a loading dose of BSI-045B (300 mg) SC QW for 4 weeks, patients will move to maintanence 300 mg SC Q2W through Week 24. There will be a 12-week Follow-up Period after treatment. A Safety Steering Committee (SSC) will monitor the study to identify questions concerning safety. The primary efficacy endpoint is the proportion of patients with ≥EASI75 at Week 26 (2 weeks after last dose at Week 24), compared with baseline (Day1). Additional efficacy outcomes also include other scores on EASI, Investigator's Global Assessment (IGA), Facial IGA, and Peak Pruritus Numerical Rating Scale (PP-NRS). Efficacy assessments will be conducted at Screening, within the first hour prior to dosing on Day 1, at all subsequent visits, and at the time of early withdrawal from the study.
Interventions
DRUGBSI-045B
Patients will be treated with BSI-045B.
Sponsors
Biosion, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Main inclusion Criteria: * In the opinion of the Investigator, the patient is capable of understanding and complying with protocol requirements. * The patient signs and dates a written ICF prior to the initiation of any study procedures. * The patient has a diagnosis of AD (according to the criteria established by Hanifin and Rajka, 1980). The diagnosis of AD must have been present for at least 1 year, and the patient's AD must have been active for at least 3 months. * The patient is aged 18 to 65 years, inclusive at the time of consent. Patients of any gender are eligible. * The EASI is ≥12 at Screening and on Day 1. * The score on the IGA is ≥3 (scale of 0 to 4) at Screening and on Day 1. * The total body surface area (BSA) affected by AD is ≥10% as assessed by the physical examination at Screening and on Day -1. * The patient has not received prior treatment with topical or systemic medications OR the patient has active disease despite topical or systemic treatment as per the Investigator at the time of screening. * A male patient who is non-sterilized and sexually active with a female partner of childbearing potential, and female patient of childbearing potential who is sexually active with a non-sterilized male partner agrees to use highly effective contraception from the time of signing the ICF throughout the duration of the study and for 90 days (\ 5 half lives) after the last dose of study drug. Main
Exclusion criteria
* The patient has another dermatologic condition that might confound a diagnosis of AD or a treatment assessment. * The patient has any clinically significant illness that may affect the safety, increase the risk for seizure or lower the seizure threshold, or potentially confound the study results. * The patient has abnormal laboratory values during the Screening Period: ALT and/or AST \> 1.5 ULN, total bilirubin ≥ 1.5 mg/dL, estimated glomerular filtration rate (GFR) \< 60 mL/min (based on Cockcroft-Gault calculation), hemoglobin≤ 10 g/dL, platelet count ≤ 150 ×103/µL, creatine kinase \> 2.5×ULN. * The patient has a history of anaphylaxis following biologic therapy. * The patient has a history of allergy to corticosteroids, diphenhydramine, hydroxyzine, cetirizine, or fexofenadine. * The patient has a history of a clinically significant infection within 4 weeks prior to Screening. * The patient has been diagnosed with a helminthic parasitic infection within 6 months prior to Screening. * The patient has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Screening or is unwilling to agree to abstain from alcohol and drugs (including cannabinoids) throughout the study. * The patient had a major surgical or major dental procedure within 8 weeks prior to Screening. * The patient is pregnant or lactating or intends to become pregnant or donate ova before, during, or within 90 days (\ 5 half-lives) since the last dose of study drug. * If male, the patient intends to donate sperm during this study or within 90 days (\ 5 half-lives) since the last dose of study drug. * The patient has a history of neurologic abnormalities including abnormal electroencephalography, brain injury including traumatic injury, perinatal cerebropathy, postnatal brain damage, blood-brain barrier abnormality, and cavernous angioma. * The patient has a history of cerebral arteriosclerosis. * The patient has a history of cancer. Patients with localized basal cell carcinoma, localized squamous cell carcinoma of the skin, or carcinoma in situ of the cervix may be included in the study if they have completed curative treatment at least 12 months prior to Screening. Patients with other malignant tumors may be included if they have completed curative treatment at least 5 years prior to the first dose of study drug. * The patient has a positive test result for hepatitis B surface antigen (HbsAg), antihepatitis C virus (HCV), a history of active tuberculosis, a positive test result for human immunodeficiency virus (HIV), or a known history of HIV infection at Screening. * The patient has poor peripheral venous access. * The patient has donated or lost ≥ 450 mL of blood (including plasmapheresis) or had a transfusion of any blood product within 90 days prior to the first dose of study drug. * The patient has an abnormal ECG at Screening or on Day -1. In the case of a corrected QT interval (Fridericia) (QTcF) \> 450 ms or \> 470 ms (patients with bundle branch block) or PR interval outside the range of 115 to 220 ms, assessment may be repeated once for eligibility determination at Screening and/or on Day -1. * The patient has a supine systolic blood pressure \< 90 or \> 144 mm Hg or a supine diastolic blood pressure \< 50 or \> 94 mm Hg at Screening or on Day -1. If out of range, assessment may be repeated once for eligibility determination at Screening and/or on Day -1. * The patient has a resting heart rate \< 40 or \> 90 bpm (not on ECGs) and considered clinically significant by the Investigator at Screening or on Day 1. If out of range, the assessment may be repeated once for eligibility determination at Screening and/or on Day -1. * The patient plans to use any other prohibited medication or undergo any prohibited procedure during the study. Oral antibiotics are permitted. Bleach baths are not permitted. * The patient has a risk of suicide on the Patient Health Questionnaire-2 (PH 2) or in the judgment of the Investigator, or the patient has made a suicide attempt or has a history of deliberate self-harm in the 6 months prior to Screening. * The patient is compulsorily detained for a medical or psychiatric illness. * The patient or their immediate family are personnel at the clinical site. * The patient is unable to comply with restrictions and prohibited activities/treatments as listed in the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 26 | Week 26 | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. |
| Safety Profile of Study Treatment | Day 1 to Week 36 | Number of Participants With Treatment-emergent Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters | Weeks 4, 24, and 26 | BSI-045B Serum Concentration |
| Immunogenicity Following BSI-045B Treatment | Day 1 to Week 36 | Number of Participants With Anti-BSI-045B Anti-drug Antibodies (ADA) Following BSI-045B Treatment |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving Facial IGA 0/1 at Week 26 | Day 1 to Week 36 | The facial IGA is an instrument used in clinical trials to rate the severity of the subject's facial AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| Exploratory Endpoint, Proportions of Patients Achieving at Least 50%, 90% Reductions in EASI | Week 26 | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. |
| Exploratory Endpoint, Conjunctivitis | Day 1 to Week 36 | Occurence of conjunctivitis |
| Percent Change From Baseline in EASI at Each Visit | Day 1 to Week 36 | The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. |
| Exploratory Endpoint, Proportion of Patients Achieving Investigator's Global Assessment (IGA) 0 or 1 at Week 26 | Day 1 to Week 36 | The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| Exploratory Endpoint, Percentage Changes in Peak Pruritus Numerical Rating Scale (PP-NRS) at Week 26 | Day 1 to Week 36 | Patients will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 300 mg BSI-045B 300 mg SC QW × 4 weeks, then BSI-045B 300 mg SC Q2W through Week 24
BSI-045B: Patients will be treated with BSI-045B. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | 300 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 43.5 years STANDARD_DEVIATION 14.27 |
| BMI | 28.08 kg/m2 STANDARD_DEVIATION 3.536 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 5 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Proportion of Patients Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 26
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Time frame: Week 26
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg | Proportion of Patients Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 26 | 94.1 percentage of patients achieved EASI75 |
Primary
Safety Profile of Study Treatment
Number of Participants With Treatment-emergent Adverse Events
Time frame: Day 1 to Week 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg | Safety Profile of Study Treatment | 13 Participants |
Secondary
Immunogenicity Following BSI-045B Treatment
Number of Participants With Anti-BSI-045B Anti-drug Antibodies (ADA) Following BSI-045B Treatment
Time frame: Day 1 to Week 36
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 300 mg | Immunogenicity Following BSI-045B Treatment | Patients with positive ADA during the study | 1 Participants |
| 300 mg | Immunogenicity Following BSI-045B Treatment | Patients with positive ADA during treatment period | 0 Participants |
| 300 mg | Immunogenicity Following BSI-045B Treatment | Patients with positive ADA during follow-up period | 1 Participants |
Secondary
Pharmacokinetic Parameters
BSI-045B Serum Concentration
Time frame: Weeks 4, 24, and 26
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg | Pharmacokinetic Parameters | serum concentration at Week 4 | 68811.694 ng/mL | Standard Deviation 23168.04 |
| 300 mg | Pharmacokinetic Parameters | serum concentration at Week 24 | 63876.475 ng/mL | Standard Deviation 27824.166 |
| 300 mg | Pharmacokinetic Parameters | serum concentration at Week 26 | 54324.171 ng/mL | Standard Deviation 25546.549 |
Other Pre-specified
Exploratory Endpoint, Conjunctivitis
Occurence of conjunctivitis
Time frame: Day 1 to Week 36
Other Pre-specified
Exploratory Endpoint, Percentage Changes in Peak Pruritus Numerical Rating Scale (PP-NRS) at Week 26
Patients will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Time frame: Day 1 to Week 36
Other Pre-specified
Exploratory Endpoint, Proportion of Patients Achieving Investigator's Global Assessment (IGA) 0 or 1 at Week 26
The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Time frame: Day 1 to Week 36
Other Pre-specified
Exploratory Endpoint, Proportions of Patients Achieving at Least 50%, 90% Reductions in EASI
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Time frame: Week 26
Other Pre-specified
Percent Change From Baseline in EASI at Each Visit
The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Time frame: Day 1 to Week 36
Other Pre-specified
Proportion of Patients Achieving Facial IGA 0/1 at Week 26
The facial IGA is an instrument used in clinical trials to rate the severity of the subject's facial AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Time frame: Day 1 to Week 36