Adalimumab Microneedles in Healthy Volunteers
Condition: Pain; Injection Site
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

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).
    

Intervention name(s): Adalimumab ID; Adalimumab SC; Saline ID; Saline SC
Intervention type(s): Biological; Biological; Other; Other
Intervention description(s): Adalimumab intradermal using MicronJet600 microneedle from NanoPass; Adalimumab subcutaneous using regular needle; Saline intradermal using MicronJet600 microneedle from NanoPass; Saline subcutaneous using regular needle
Intervention MeSH terms: Adalimumab
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double blind, placebo controlled, double-dummy study.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: intradermal; adalimumab; microneedle; subcutaneous; healthy volunteers