Ignite Creation Date:
2024-05-06 @ 3:45 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04744363
Status:
COMPLETED
Last Update Posted:
2022-05-23
First Post:
2020-12-16
Brief Title:
Pharmacokinetics Safety and Tolerability Study of AVT04 to EU Approved and US Licensed Stelara Ustekinumab
Sponsor:
Alvotech Swiss AG
Organization:
Alvotech Swiss AG
Study Overview
Official Title:
Phase 1 FIH Randomized Double-blind Single-dose Parallel-group 3-arm Study Comparing the PK Safety Tolerability and Immunogenicity Profiles of AVT04 EU-approved Stelara and US-licensed Stelara in Healthy Adult Subjects
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Protocol Title
A Phase 1 first-in-human randomized double-blind single-dose parallel-group 3-arm study comparing the pharmacokinetic safety tolerability and immunogenicity profiles of AVT04 EU approved Stelara and US-licensed Stelara in healthy adult subjects
Short Title
A first-in-human randomized double-blind study to compare AVT04 with EU-approved Stelara and US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects
Rationale
Alvotech hereafter the Sponsor is developing AVT04 globally as a proposed biosimilar to the reference product Stelara ustekinumab for subcutaneous SC use This is a first-in-human FIH clinical study with AVT04 The study aims to demonstrate pharmacokinetic PK similarity of the proposed biosimilar test product AVT04 and the reference products EU approved Stelara and US-licensed Stelara in addition to evaluating the safety and tolerability of AVT04 when administered as a single 45 mg05 mL SC dose
A Phase 1 first-in-human randomized double-blind single-dose parallel-group 3-arm study comparing the pharmacokinetic safety tolerability and immunogenicity profiles of AVT04 EU approved Stelara and US-licensed Stelara in healthy adult subjects
Short Title
A first-in-human randomized double-blind study to compare AVT04 with EU-approved Stelara and US-licensed Stelara as a single-dose subcutaneous injection in healthy adult subjects
Rationale
Alvotech hereafter the Sponsor is developing AVT04 globally as a proposed biosimilar to the reference product Stelara ustekinumab for subcutaneous SC use This is a first-in-human FIH clinical study with AVT04 The study aims to demonstrate pharmacokinetic PK similarity of the proposed biosimilar test product AVT04 and the reference products EU approved Stelara and US-licensed Stelara in addition to evaluating the safety and tolerability of AVT04 when administered as a single 45 mg05 mL SC dose
Detailed Description:
Overall Design
This study is designed as a FIH multicenter randomized double-blind 3-arm parallel-group study of AVT04 compared with EU-approved and US-licensed Stelara when administered as a single 45 mg05 mL SC injection in healthy adult subjects
Subjects will undertake a Screening visit between Day -28 and Day -1 to determine their eligibility in the study Subjects who meet the eligibility criteria will be admitted to the study site on the day prior to dosing Day -1 during which their continued eligibility will be assessed up to Day 1 prior to dosing On Day 1 eligible subjects will be randomized and will receive a single dose of one of the following AVT04 US licensed Stelara or EU approved Stelara
A staggered sentinel dosing strategy will be implemented as a safety measure with equal numbers of subjects randomized to each treatment Sentinel Group 1 n 3 subjects 1 per group Sentinel Group 2 n 6 subjects 2 per group and Sentinel Group 3 n 9 subjects 3 per group Following investigational product IP administration there will be at least 72 hours of close observation and safety monitoring by the Principal Investigator PI for each subject and between sentinel groups ie 72 hours should have elapsed following IP administration for the last subject in each sentinel group Provided there are no significant safety or tolerability concerns or events that meet the study stopping criteria in the previous sentinel group following a safety review and discussion between the PI Medical Monitor and Sponsor the next sentinel group of subjects will be randomized and dosed Once the IP dose is deemed to be safe and well tolerated in all 3 sentinel groups the remaining subjects n 276 subjects 92 subjects per group will be randomized and dosed
Sentinel subjects will remain confined to the study site from Day -1 to Day 4 72 hours postdose all remaining subjects will be confined to the study site from Day -1 up to Day 2 24 hours postdose Following dosing PK safety tolerability and other assessments will be performed according to the Schedule of Assessments Subjects will return to the study site on an outpatient basis daily up to Day 12 then once a week from Day 15 to Day 64 followed by once every 2 weeks up to Day 78 and finally on Day 92 for the End-of-Study EOS visit
Number of Subjects
Approximately 294 healthy subjects 98 per group are planned to be enrolled at multiple study sites in New Zealand and Australia Efforts will be made to include at least 10 of subjects 30 subjects approximately 10 per group who are of Japanese origin or ethnicity defined as a second-generation Japanese person living abroad or born in Japan and both parents and grandparents are of Japanese origin
A total of 45 subjects 15 per group are planned to be included in the exploratory ex-vivo biomarker sub study
Treatment Groups and Duration
Eligible subjects will be randomly assigned in a 111 ratio to receive a single 45 mg05 mL SC dose of ustekinumab as AVT04 test product or US licensed Stelara or EU approved Stelara reference products on Day 1 Randomization will be stratified by ethnicity and body weight at Day -1 as follows Japanese non Japanese 80 kg and non-Japanese 80 kg
The study duration per subject will be approximately 17 weeks The study will consist of a 4 week Screening period a 13-week treatment period and assessment period and an EOS visit on Day 92
Study Stopping Criteria
If either of the following scenarios occur study enrollment and dosing will be halted
If 2 subjects experience a suspected unexpected serious adverse reaction defined as an adverse event AE that is serious unexpected and considered related to the IP
If the Sponsor or Investigator considers there to be an unfavorable benefit-risk ratio based on emerging safety data
If following consultation between the PI Medical Monitor and Sponsor it is considered appropriate to restart study drug administration in the remaining subjects justification will be submitted to the Health and Disability Ethics CommitteeHuman Research Ethics Committee for restarting the study
This study is designed as a FIH multicenter randomized double-blind 3-arm parallel-group study of AVT04 compared with EU-approved and US-licensed Stelara when administered as a single 45 mg05 mL SC injection in healthy adult subjects
Subjects will undertake a Screening visit between Day -28 and Day -1 to determine their eligibility in the study Subjects who meet the eligibility criteria will be admitted to the study site on the day prior to dosing Day -1 during which their continued eligibility will be assessed up to Day 1 prior to dosing On Day 1 eligible subjects will be randomized and will receive a single dose of one of the following AVT04 US licensed Stelara or EU approved Stelara
A staggered sentinel dosing strategy will be implemented as a safety measure with equal numbers of subjects randomized to each treatment Sentinel Group 1 n 3 subjects 1 per group Sentinel Group 2 n 6 subjects 2 per group and Sentinel Group 3 n 9 subjects 3 per group Following investigational product IP administration there will be at least 72 hours of close observation and safety monitoring by the Principal Investigator PI for each subject and between sentinel groups ie 72 hours should have elapsed following IP administration for the last subject in each sentinel group Provided there are no significant safety or tolerability concerns or events that meet the study stopping criteria in the previous sentinel group following a safety review and discussion between the PI Medical Monitor and Sponsor the next sentinel group of subjects will be randomized and dosed Once the IP dose is deemed to be safe and well tolerated in all 3 sentinel groups the remaining subjects n 276 subjects 92 subjects per group will be randomized and dosed
Sentinel subjects will remain confined to the study site from Day -1 to Day 4 72 hours postdose all remaining subjects will be confined to the study site from Day -1 up to Day 2 24 hours postdose Following dosing PK safety tolerability and other assessments will be performed according to the Schedule of Assessments Subjects will return to the study site on an outpatient basis daily up to Day 12 then once a week from Day 15 to Day 64 followed by once every 2 weeks up to Day 78 and finally on Day 92 for the End-of-Study EOS visit
Number of Subjects
Approximately 294 healthy subjects 98 per group are planned to be enrolled at multiple study sites in New Zealand and Australia Efforts will be made to include at least 10 of subjects 30 subjects approximately 10 per group who are of Japanese origin or ethnicity defined as a second-generation Japanese person living abroad or born in Japan and both parents and grandparents are of Japanese origin
A total of 45 subjects 15 per group are planned to be included in the exploratory ex-vivo biomarker sub study
Treatment Groups and Duration
Eligible subjects will be randomly assigned in a 111 ratio to receive a single 45 mg05 mL SC dose of ustekinumab as AVT04 test product or US licensed Stelara or EU approved Stelara reference products on Day 1 Randomization will be stratified by ethnicity and body weight at Day -1 as follows Japanese non Japanese 80 kg and non-Japanese 80 kg
The study duration per subject will be approximately 17 weeks The study will consist of a 4 week Screening period a 13-week treatment period and assessment period and an EOS visit on Day 92
Study Stopping Criteria
If either of the following scenarios occur study enrollment and dosing will be halted
If 2 subjects experience a suspected unexpected serious adverse reaction defined as an adverse event AE that is serious unexpected and considered related to the IP
If the Sponsor or Investigator considers there to be an unfavorable benefit-risk ratio based on emerging safety data
If following consultation between the PI Medical Monitor and Sponsor it is considered appropriate to restart study drug administration in the remaining subjects justification will be submitted to the Health and Disability Ethics CommitteeHuman Research Ethics Committee for restarting the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None