Safety and Tolerability of BSI-045B in Healthy Adult Subjects and Patients With Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial to Evaluate Safety and Tolerability of BSI-045B mAb Injection in Healthy Adult Subjects and Patients With Atopic Dermatitis

Status Completed

Clinical Trial 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

Clinical Trial 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). ;

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

• NCT number: NCT05114889
• Study type: Interventional
• Source: Biosion, Inc.
• Status: Completed
• Phase: Phase 1
• Start date: October 25, 2021
• Completion date: February 15, 2023