Ignite Creation Date:
2025-12-24 @ 7:23 PM
Ignite Modification Date:
2025-12-25 @ 5:02 PM
Study NCT ID:
NCT03607903
Status:
COMPLETED
Last Update Posted:
2021-08-03
First Post:
2018-06-08
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Adalimumab Microneedles in Healthy Volunteers
Sponsor:
Centre for Human Drug Research, Netherlands
Organization:
Study Overview
Official Title:
A Randomized, Double Blind, Placebo-controlled, Double-dummy Study to Assess Microneedle Delivery in Comparison to Subcutaneous Injection of Adalimumab in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2021-08
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:
Adalimumab (Humira, AbbVie) is a highly effective treatment for a variety of auto-immune/auto-inflammatory diseases including juvenile idiopathic arthritis (JIA). Adalimumab works by binding to tumor necrosis factor alpha (TNF), hereby preventing its interaction with the TNF receptor. In the presence of complement, adalimumab can also lyse TNF-expressing cells.
Adalimumab is administered via subcutaneous injection, which has the major drawback of being perceived as unpleasant and painful, especially during long term use for both adults and children. As subcutaneous administration may therefore eventually jeopardize treatment adherence, there is a clear need for less invasive alternatives to administer highly effective biological drugs such as adalimumab.
Microneedles may be a potential alternative for invasive drug administration. Microneedles are currently widely investigated for the administration of various vaccines. The experience with administration of biological drugs is rather limited. The sparse available data suggests similar pharmacokinetics of adalimumab when administered either subcutaneous or intradermal in healthy volunteers. Moreover, the first studies report good tolerability of microneedles. However, no systematic studies have been performed yet i) to investigate pain, acceptability, and local tolerability for intradermal versus subcutaneous adalimumab administration ii) to evaluate safety, PK and immunogenicity for intradermal versus subcutaneous adalimumab and iii) to explore the usability of optical coherence tomography, clinical photography, thermal imaging and laser speckle contrast imaging in the evaluation of intradermal injections.
This study will directly compare the pain perception and hence acceptability of a single dose (40 mg) of adalimumab administered subcutaneously (SC) versus intradermally (ID) via microneedles in healthy adult volunteers. Furthermore, the pharmacokinetic profile, pharmacodynamics, the immunogenicity and the tolerability will be assessed. This study will enable bridging to a future study in children and adolescents with JIA, in which the suitability of microneedles for the administration of adalimumab in pediatric patients will be examined. The overarching aim of these studies is to make administration of biologicals in children as pain free as possible.
Adalimumab is administered via subcutaneous injection, which has the major drawback of being perceived as unpleasant and painful, especially during long term use for both adults and children. As subcutaneous administration may therefore eventually jeopardize treatment adherence, there is a clear need for less invasive alternatives to administer highly effective biological drugs such as adalimumab.
Microneedles may be a potential alternative for invasive drug administration. Microneedles are currently widely investigated for the administration of various vaccines. The experience with administration of biological drugs is rather limited. The sparse available data suggests similar pharmacokinetics of adalimumab when administered either subcutaneous or intradermal in healthy volunteers. Moreover, the first studies report good tolerability of microneedles. However, no systematic studies have been performed yet i) to investigate pain, acceptability, and local tolerability for intradermal versus subcutaneous adalimumab administration ii) to evaluate safety, PK and immunogenicity for intradermal versus subcutaneous adalimumab and iii) to explore the usability of optical coherence tomography, clinical photography, thermal imaging and laser speckle contrast imaging in the evaluation of intradermal injections.
This study will directly compare the pain perception and hence acceptability of a single dose (40 mg) of adalimumab administered subcutaneously (SC) versus intradermally (ID) via microneedles in healthy adult volunteers. Furthermore, the pharmacokinetic profile, pharmacodynamics, the immunogenicity and the tolerability will be assessed. This study will enable bridging to a future study in children and adolescents with JIA, in which the suitability of microneedles for the administration of adalimumab in pediatric patients will be examined. The overarching aim of these studies is to make administration of biologicals in children as pain free as possible.
Detailed Description:
Objective(s)
1. To evaluate the pain, acceptability and local tolerability of intradermal microneedle injection compared to subcutaneous injection in healthy volunteers.
2. To evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of adalimumab after administration using microneedles versus subcutaneous injection in healthy volunteers.
3. To explore the usability of optical coherence tomography, clinical photography, laser speckle contrast imaging, and thermal imaging in the evaluation of intradermal injections.
Definitions Method: ID or SC injection Compound: adalimumab or saline Treatment: combination of method and compound Arm: sequence of treatments
Design This is a double blind, placebo controlled, double-dummy study. The study physician will administer the injection and is thus unblinded to the type of injection. All injection site assessments will be performed by (a) study independent member of the clinical staff.
Sterile saline injection will be used as a negative control. Subjects will receive an injection with both sterile saline (SC or ID) and adalimumab (SC or ID). Subjects will be randomized to one of the four arms:
1A) adalimumab SC and saline ID
1. B) saline ID and adalimumab SC
2. A) saline SC and adalimumab ID
2B) adalimumab ID and saline SC
The maximum duration between treatments will be 5 minutes.
After a single dose of adalimumab, pharmacokinetic, pharmacodynamics, tolerability and immunogenicity data will be collected and monitored for a total of 70 days post dose, as the half-life of adalimumab after subcutaneous injection in adults is approximately two weeks.
Investigational drug/device combination In children, adalimumab is commonly used in a dose of 40 mg SC every two weeks (1). For adults with rheumatoid arthritis the same dose is used (2). It was therefore chosen to administer adalimumab in a single dose of 40 mg in 0.4 mL either subcutaneously or intradermally in the upper thigh. For saline injection the same volume will be used.
For intradermal administration, the MicronJet600 (NanoPass Technologies) will be used (hereafter referred to as microneedle). This CE-marked microneedle consists of an array of three hollow pyramid-shaped microneedles with a length of 600 micrometer (3).
Subjects / Groups A total of 24 healthy subjects (N=6 per arm and N=12 per treatment (Adalimumab SC, Adalimumab ID, Saline SC, Saline ID).
1. To evaluate the pain, acceptability and local tolerability of intradermal microneedle injection compared to subcutaneous injection in healthy volunteers.
2. To evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of adalimumab after administration using microneedles versus subcutaneous injection in healthy volunteers.
3. To explore the usability of optical coherence tomography, clinical photography, laser speckle contrast imaging, and thermal imaging in the evaluation of intradermal injections.
Definitions Method: ID or SC injection Compound: adalimumab or saline Treatment: combination of method and compound Arm: sequence of treatments
Design This is a double blind, placebo controlled, double-dummy study. The study physician will administer the injection and is thus unblinded to the type of injection. All injection site assessments will be performed by (a) study independent member of the clinical staff.
Sterile saline injection will be used as a negative control. Subjects will receive an injection with both sterile saline (SC or ID) and adalimumab (SC or ID). Subjects will be randomized to one of the four arms:
1A) adalimumab SC and saline ID
1. B) saline ID and adalimumab SC
2. A) saline SC and adalimumab ID
2B) adalimumab ID and saline SC
The maximum duration between treatments will be 5 minutes.
After a single dose of adalimumab, pharmacokinetic, pharmacodynamics, tolerability and immunogenicity data will be collected and monitored for a total of 70 days post dose, as the half-life of adalimumab after subcutaneous injection in adults is approximately two weeks.
Investigational drug/device combination In children, adalimumab is commonly used in a dose of 40 mg SC every two weeks (1). For adults with rheumatoid arthritis the same dose is used (2). It was therefore chosen to administer adalimumab in a single dose of 40 mg in 0.4 mL either subcutaneously or intradermally in the upper thigh. For saline injection the same volume will be used.
For intradermal administration, the MicronJet600 (NanoPass Technologies) will be used (hereafter referred to as microneedle). This CE-marked microneedle consists of an array of three hollow pyramid-shaped microneedles with a length of 600 micrometer (3).
Subjects / Groups A total of 24 healthy subjects (N=6 per arm and N=12 per treatment (Adalimumab SC, Adalimumab ID, Saline SC, Saline ID).
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: