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…
ID
Source
Brief title
Condition
- Other condition
- Immune disorders NEC
Synonym
Health condition
Route of administration
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety endpoints
- (Serious) adverse events ((S)AE)
- Vital signs and clinical laboratory assessment
- ECG
- Locale tolerance:
1) VAS for pain, separate for injection and insertion pain, using (1) the Faces
Pain Scales Revised (official Dutch translation); (2) 100 points VAS;
2) Irritation; itching; spontaneous reporting;
3) Clinical evaluation in a standardized manner by physician (appendix 1).
- Clinical imaging of the skin: these data might provide insight into the
mechanisms of intradermal drug delivery and might serve as future comparison
for other studies examining intradermal administration of biologicals. The
following assessments will be performed:
* Clinical photography
* Thermal imaging
* Optical coherence tomography
* Laser speckle contrast imaging
Immunogenicity endpoint
- Formation of anti-adalimumab antibodies (AAA)
Acceptability endpoints
- Questionnaire on perception, convenience, and fear for injection
Pharmacokinetic endpoints
- Area under the concentration-time curve (AUC);
- Maximal concentration (Cmax);
- Time to maximal concentration (Tmax);
- Half-life (T1/2);
- Clearance (Cl);
- Bioavailability (F).
Pharmacodynamic endpoints
- Ex vivo cytokine levels
Secondary outcome
N.A.
Background 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.
Study objective
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, and thermal imaging in the evaluation of intradermal injections
Study 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
1B) saline ID and adalimumab SC
2A) 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
Intervention
Adalimumab
Study burden and risks
Burden: measurements, SC and ID injections, local irritability, blood sampling,
lifestyle restrictions and time investment.
Risks: potential adverse events
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Eligible subjects must meet all of the following inclusion criteria at screening:
1) Healthy male / female subjects, 18 to 45 years of age, inclusive at screening;
2) Good health, based upon the results of medical history, physical examination, vital signs, ECG, and laboratory profiles of both blood and urine;
3) Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg;
4) Willing to practice an approved method of birth control and not breastfeeding throughout the study and for five months after study drug administration, as advised in the drug formulary (2). If the trial subject is female, surgical sterilization or postmenopausal status for >1 year will satisfy this requirement. All female subjects are required to have a negative pregnancy test at screening and at baseline (pre-dose);
5) Fitzpatrick skin type I-II (Caucasian type);
6) Suitable site for intradermal injection on the legs, as assessed by the investigator;
7) Able and willing to provide written informed consent.
Exclusion criteria
Eligible subjects must meet none of the following exclusion criteria at screening:
1) Immune-compromised (known or expected immune deficiency, disease, or use of medication that may affect the immune system);
2) Diagnosed with tuberculosis (TB, as per positive skin test [Mantoux] or interferon gamma release assay), or history of TB, or latent TB, or recent contact with TB (patient); having travelled to countries where TB is endemic within eight weeks of planned drug administration or planning to travel to countries where TB is endemic from the moment of drug administration until three months after the end of the study;
3) Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug (including adalimumab);
4) History of chronic infection, or infections within the past two years requiring hospitalization or administration of intravenous antibiotics;
5) Receipt of any live vaccination within three months prior to study drug administration, or intention to undergo live vaccinations from the moment of drug administration until four months after the end of study;
6) Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening;
7) Evidence of any active or chronic disease (hematologic, renal, hepatic, cardiovascular, neurologic, endocrinal, gastrointestinal, oncologic, pulmonary, immunologic, or psychiatric disorder) or condition that could interfere with, or for which the treatment of might interfere with the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, and body temperature) and ECG). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance;
8) History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent;
9) Consumption of alcohol within the 48-hour period prior to study drug administration;
10) Smoke more than 10 cigarettes per day prior to screening or use tobacco products equivalent to more than 10 cigarettes per day and/or unable to abstain from smoking whilst in the unit;
11) Positive screen for recreational drugs or alcohol;
12) Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day);
13) Unlikely to comply with the study protocol and/or to complete the study or required study procedures, including being unlikely or unable to return for follow-up visits;
14) Use of any medication (prescription or over-the-counter (OTC) within 14 days of study drug administration, or use of herbal supplements, dietary supplements or multivitamins within 7 days of study drug administration or less than five half-lives (whichever is longer), or receipt of any drug by injection within 30 days of study drug administration, with the exception of contraceptives, hormonal replacement therapies, and paracetamol (up to 4g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator;
15) Donation of over 500 mL of blood within three months prior to screening or donation of plasma within 14 days prior to screening;
16) Previous exposure to any biological;
17) Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year;
18) 18) Excessive sun exposure of the injection site area within 3 weeks of enrollment;
19) Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive adalimumab or otherwise participate in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001533-41-NL |
| CCMO | NL65800.056.18 |