Safety and Tolerability of BSI-045B in Healthy Adult Subjects and Patients With Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Study type: Interventional
Phase: Phase 1

Summary: 
      This randomized, double-blind, single center, placebo-controlled, phase 1 single ascending
      dose (SAD)/multiple ascending dose (MAD) study is designed to assess the safety,
      tolerability, PK, activity, immunogenicity, and PD of BSI-045B. Approximately 68 subjects
      will be enrolled. Subjects in this study include 56 healthy volunteers (HVs) and 12 patients
      with AD.

      This study is divided into 3 parts:

        1. Part A: Evaluate the safety, tolerability, PK, immunogenicity, and PD of single
           ascending doses of BSI-045B administered as a subcutaneous (SC) injection of 120, 240,
           480, and 720 mg to HVs

        2. Part B: Evaluate the safety, tolerability, PK, activity (as measured by the Eczema Area
           and Severity Index [EASI] score), immunogenicity, and PD of a single dose of BSI-045B
           administered as a SC injection of 480 mg to patients with AD

        3. Part C: Evaluate the safety, tolerability, PK, immunogenicity, and PD of multiple
           ascending doses of BSI-045B administered as five (5) SC injections of 240, 480, and 600
           mg every 7 days (Q7D) to HVs
    

Detailed description: 
      This study is a phase 1 clinical study to evaluate the safety, tolerability, immunogenicity,
      PK profile, activity, and PD of BSI-045B injection after single/multiple doses in adult HVs
      and patients with AD using a randomized, double-blind, placebo-controlled design. It consists
      of 3 parts: a SAD study in HVs, a single dose study in patients with AD, and a MAD study in
      HVs.

      Part A: Single Ascending Dose in HVs The SAD study in HVs will consist of single ascending
      doses in a 4-cohort design. Cohorts 1, 2, 3, and 4 will each consist of 8 HVs (6 Active: 2
      Placebo). The total number of HVs to be enrolled in Part A is 32.

      Subjects in Part A will be enrolled as follows:

      Cohort 1: HVs (Active:Placebo 6:2), 120 mg, single dose; n = 8 Cohort 2: HVs (Active:Placebo
      6:2), 240 mg, single dose; n = 8 Cohort 3: HVs (Active:Placebo 6:2), 480 mg, single dose; n =
      8 Cohort 4: HVs (Active:Placebo 6:2), 720 mg, single dose; n = 8 The preferred SC injection
      site is the abdomen. Multiple SC injections required for higher dose cohorts should be
      administered no more than 1 minute apart. The thigh can be used as an alternative site for SC
      injections. In Cohort 1, a 1 mL injection of 120 mg/mL (120 mg total dose) will be
      administered at a single SC injection site. In Cohort 2, a 2 mL injection of 120 mg/mL (240
      mg total dose) will be administered at a single SC injection site. In Cohort 3, two 2 mL
      injections of 120 mg/mL will be administered simultaneously at 2 separate SC injection sites
      for a total of 4 mL (480 mg total dose). In Cohort 4, three 2 mL injections of 120 mg/mL will
      be administered simultaneously at three separate SC injection sites, for a total of 6 mL (720
      mg total dose).

      Part B: Single Dose in Patients with AD The total number of patients with AD to be enrolled
      in the single-dose study in Part B is 12.

      Following a thorough assessment of safety, tolerability, and PK at Week 11 and Week 12 of the
      HVs treated with 480 mg in Part A, subjects will be enrolled into Part B (so that Day 1 of
      Part B will correspond to Day 1 of Week 13 of Part A).

      Patients with AD will be enrolled as follows:

      Cohort 1: Patients with AD (Active:Placebo 9:3), 480 mg, single dose; n = 12 The preferred SC
      injection site is the abdomen. Injections should be administered no more than 1 minute apart.
      The thigh can be used as an alternative site for SC injections. Patients with AD will be
      administered two separate 2 mL injections of 120 mg/mL simultaneously at two separate SC
      injection sites, for a total of 4 mL (480 mg total dose).

      Management of SAD HV Cohort (Part A) and Single-Dose Cohort, Patients with AD (Part B)
      Healthy volunteers and patients with AD will be admitted to the phase 1 clinical site 1 day
      before each dose administration. In this phase 1 study of BSI-045B, sentinel dosing will be
      used for each of the SAD cohorts. The first 2 HVs and AD patients in each cohort will receive
      either BSI-045B or placebo in parallel (1 Active:1 Placebo), followed by a 3 day gap to allow
      for the evaluation of safety and tolerability before administering the same dose of BSI-045B
      or placebo to the remaining HVs (5 Active:1 Placebo) or AD patients (8 Active:2 Placebo).

      Healthy volunteers and patients with AD will be confined at the clinical site to assess
      tolerability, safety, and adverse events (AEs), and for collection of blood samples for PK
      analysis. After 9 days of evaluation, HVs or patients with AD will leave the phase 1 clinic
      after completion of the clinical assessments. Follow-up visits at scheduled time points will
      be conducted to evaluate safety, tolerability, PK, immunogenicity, and biomarkers.

      All decisions concerning dose escalation will be made by a Safety Review Committee composed
      of representatives from Biosion (at a minimum, the clinical science representative and
      pharmacovigilance physician, or appropriate delegates), the Principal Investigator and an
      independent member. The Investigator, Biosion personnel, and HVs or patients will remain
      blinded throughout the study. Pharmacy staff preparing the study medications will be
      unblinded. If unblinding is necessary for a specific subject, emergency unblinding may be
      arranged after approved by the Principal Investigator and discussed with the Medical Monitor.
      Dose escalation meetings will be carried out in accordance with the Safety Review Committee
      Charter.

      Follow-up assessments will occur on Day 15 and during subsequent visits to the clinic for PK
      blood draws through Day 113 (the termination of each cohort in the SAD study). Adverse events
      will be collected through Day 113 to determine whether there are ongoing AEs, serious adverse
      events (SAEs), worsening of AEs or SAEs, or development of new AEs or SAEs. Concomitant
      medications taken after the final dose of BSI-045B or placebo will be recorded through Day
      113. Follow-up will occur during clinic visits and if abnormal, clinically significant
      findings are observed upon discharge. At the Investigator's discretion, volunteers may be
      brought back to the clinic for re-evaluation.

      Part C: Multiple Ascending Doses in HVs The MAD study will consist of multiple ascending
      doses in 3 cohorts. Cohorts 1, 2, and 3 will consist of 8 HVs (6 Active:2 Placebo). The MAD
      study will enroll a total of 24 HVs.

      The MAD Part C portion of the study will commence after pharmacokinetic and safety
      information from the 2nd cohort (240 mg total dose) of the HV SAD portion of the study has
      been evaluated and approved by the Safety Review Committee. Sequential groups of HVs will
      receive SC injections of BSI-045B Q7D for a total of 5 doses. BSI-045B (or placebo) will be
      administered as single- or multiple-site SC injection(s).

      Subjects in Part C will be enrolled as follows:

      Cohort 1: HVs (Active:Placebo 6:2), 240 mg Q7D, 5 doses; n = 8 Cohort 2: HVs (Active:Placebo
      6:2), 480 mg Q7D, 5 doses; n = 8 Cohort 3: HVs (Active:Placebo 6:2), 600 mg Q7D, 5 doses; n =
      8 Healthy volunteers will be admitted to the phase 1 clinical site 1 day before each dose
      administration and will be discharged on Day 9 (after dose 2 on Day 8), the following day, 24
      h post-dose for doses 3 and 4 and on Day 37 after dose 5. BSI-045B or placebo will be
      administered in the morning of the first day of each administration. The preferred SC
      injection site is the abdomen. Multiple SC injections required for higher dose cohorts should
      be administered no more than 1 minute apart. The thigh can be used as an alternative site for
      SC injections. For each dose administration, SC dosing should alternate between the left and
      right sides of the abdomen or left and right thigh. In Cohort 1 (240 mg), a 2 mL injection of
      120 mg/mL will be administered at a single SC injection site. For Cohort 2 (480 mg), two 2 mL
      injections of 120 mg/mL of drug or placebo will be administered simultaneously at two
      separate SC injection sites, for a total of 4 mL. In Cohort 3 (600 mg), two separate 2 mL
      injections of 120 mg/mL of drug or placebo and a 1 mL injection of 120 mg/mL will be
      administered simultaneously at 3 separate SC injection sites, for a total of 5 mL.

      Healthy volunteers will be confined to the clinic to assess safety, tolerability, PK, and
      immunogenicity. Adverse events will be recorded and blood samples will be collected for PK
      analysis. After 9 days of evaluation, HVs will leave the phase 1 clinic after the PK blood
      draw. Follow-up visits will be conducted at scheduled time points. HVs will return for
      admission to the unit 1 day prior to dosing for doses 3, 4 and 5 on Days 15, 22, and 29
      respectively, and will be discharged 24 h post dose after doses 3 and 4 and on Day 37 after
      the final dose (dose 5).
    

Intervention name(s): BSI-045B
Intervention type(s): Biological
Intervention description(s): BSI-045B will be administered weekly, subcutaneously
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment