Microneedle Patch Study in Healthy Infants/Young Children

Study Overview
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Brief Summary
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Microneedles can be prepared as a low-cost patch that is simple for patients to apply for vaccine delivery targeting the many antigen-presenting cells present in the skin. Data regarding the safety, reactogenicity, tolerability, and acceptability of a microneedle patch in children are lacking. The goal of this study is to evaluate the safety, reactogenicity, and acceptability of placement of a placebo microneedle patch to the skin of children.

Detailed Description
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Available vaccine delivery methods include intramuscular or subcutaneous injection are limited by patient needle phobia and the need for trained medical personnel. Alternative routes of vaccination that avoid hypodermic needles have previously been poorly immunogenic, require live vaccines, utilize bulky devices and/or are unsuitable for self-administration. Novel vaccine delivery methods such as microneedles can render vaccination easier and more acceptable to the public by simplifying vaccine access. Microneedles are micron-scale needles that administer vaccine directly into the skin using a simple minimally invasive approach without generating sharps waste. This study is designed to investigate the safety, reactogenicity, and acceptability of a placebo microneedle patch in children.

Official Title
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A Study to Evaluate the Safety, Reactogenicity, and Acceptability of a Placebo Microneedle Patch in Healthy Infants and Young Children

Conditions
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Vaccination, Skin Absorption

Intervention / Treatment
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* Device: Microneedle Formulation 1
* Device: Microneedle Formulation 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Legally Authorized Representative (LAR) provides written informed consent prior to any study procedures being performed. Subject is between the ages of 6 weeks and 24 months, inclusive, on the day of signing informed consent. Subject is in good health as determined by vital signs, medical history, and a targeted physical examination. LAR is able to understand and comply with required study procedures. Exclusion Criteria: Subject has an acute illness with fever (temperature >100.4 °F) within 72 hours prior to enrollment. Subject has a known chronic medical problem. Subject has known immunosuppression due to underlying illness or treatment, including (but not limited to): Human Immunodeficiency Virus (or birth to a HIV-positive mother), hepatitis B or C; organ transplant; active cancer or any history of hematologic cancer; receipt of chemotherapy or radiation therapy; congenital immunodeficiency, anatomical or functional asplenia. Subject has used long-term* high-dose** oral or parenteral glucocorticoids, or high-dose inhaled steroids.*** * Long term is defined as taken for 2 weeks or more in total at any time during the past 2 months. ** High dose defined as prednisone ≥ 20 mg total daily dose, or equivalent dose of other glucocorticoids. *** High dose defined as >800 mcg/day of beclomethasone dipropionate or equivalent. Subject has a history of an underlying skin condition (e.g., eczema, atopic dermatitis) or an open lesion (e.g., laceration, abrasion), scar, or rash in the areas of the planned microneedle patch administration which will interfere with the assessment of reactogenicity. Subject or family members have a history of keloid formation. Subject has any condition that, in the opinion of the investigator, may put the subject at increased risk of harm, may cause the subject to be unable to meet the requirements or might otherwise interfere with evaluations required by the study. Subject has received any experimental products within 30 days before study entry or plan to receive experimental products at any time during the study. Subject has received a vaccine within 7 days of enrollment or plans to receive a vaccine within 7 days after enrollment. Subject has previously received immunoglobulin or blood products.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participating infants and children will receive Microneedle Formulation 1. At least 4 infants or children must complete Day 8 without halting criteria having been met before subjects will be enrolled into the next younger age group within a Cohort. At least the first 2 children will have a microneedle patch initially applied to the skin overlying the shoulder blade. If this site is well tolerated without halting criteria having been met additional microneedle patches may be applied to the same participants and in subsequent participants to the upper arm, forearm, wrist and/or thigh. | Device: Microneedle Formulation 1<br>* Microneedle patches will be made of solid conical structures made of water-soluble excipients that from the Food and Drug Administration's Generally Recognized as Safe (GRAS) list and/or on the FDA list of inactive ingredients in approved products. The total mass of excipients delivered by placebo microneedle patch will be <1.5 mg. The adhesive backing component is made from hypoallergenic material (commercial medical tapes designed to adhere to skin). Microneedle patches will be administered topically by manual application to the skin. The sites of microneedle patch application will be cleaned with an alcohol swab and allowed to dry before the microneedle patch is applied. The microneedle patches will be packaged and provided as single patches.<br>|
| Experimental: Cohort 2<br>Participating infants and children will receive Microneedle Formulation 2. At least 4 infants or children must complete Day 8 without halting criteria having been met before subjects will be enrolled into the next younger age group within a Cohort. At least the first 2 children will have a microneedle patch initially applied to the skin overlying the shoulder blade. If this site is well tolerated without halting criteria having been met additional microneedle patches may be applied to the same participants and in subsequent participants to the upper arm, forearm, wrist and/or thigh. | Device: Microneedle Formulation 2<br>* Microneedle patches will be made of solid conical structures made of water-soluble excipients that from the Food and Drug Administration's Generally Recognized as Safe (GRAS) list and/or on the FDA list of inactive ingredients in approved products. The ratio of the excipients and excipients used will vary slightly from Formulation 1. The total mass of excipients delivered by placebo microneedle patch will be <1.5 mg. The adhesive backing component is made from hypoallergenic material (commercial medical tapes designed to adhere to skin). Microneedle patches will be administered topically by manual application to the skin. The sites of microneedle patch application will be cleaned with an alcohol swab and allowed to dry before the microneedle patch is applied. The microneedle patches will be packaged and provided as single patches.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Placebo Microneedle Patch-related Serious Adverse Events (SAE). | To evaluate safety following application of the patch topically, microneedle patch-related serious adverse events were recorded. Information collected included event description, date of onset, severity and date of resolution/stabilization of the event. Severity and relationship to study product was assessed by the Investigator or sub-investigator. | Day 1 through the Final Study Visit (Day 27 - 38) | 
| Number of Participants With Grade 3 Placebo Microneedle Patch-related Solicited Adverse Events (AE). | The occurrence of Grade 3 solicited adverse events related to the placebo microneedle patch was recorded. Solicited adverse events were irritability (fussiness), lethargy (drowsiness), decreased appetite, vomiting, and fever. The severity of these adverse events was graded on a scale from 0 to 3 where 0 = not present and 3 = significant, preventing daily activity or a fever of >102.1 degrees Fahrenheit (F). | Up to Day 8 for Patch 1, Day 8 to Day 15 if received Patches 2 and 3 | 
| Number of Participants With Solicited Application Site Reactogenicity Events. | The occurrence of solicited reactogenicity events at the application site was recorded. The solicited reactogenicity events are reactions that are common or expected to occur with application of a microneedle patch and include induration/swelling, erythema, ecchymosis, itching, pain, and tenderness. The Legally Authorized Representatives (LARs) of participants were provided with a memory aid, thermometer and ruler to record the presence of solicited symptoms and oral temperature. Reactogenicity event details were collected via review of the subject's memory aid and by interview with the subject LAR. Reactogenicity events were graded on a scale from 0 (not present) to 3 (significant or severe). | Up to Day 8 for Patch 1, Day 8 to Day 15 if received Patches 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 Placebo Microneedle Patch-related Unsolicited Adverse Events | Grade 3, patch-related unsolicited adverse events (AEs) were recorded. An adverse event is graded as Grade 3 if the event is significant or prevents daily activity. | Day 1 through the Final Study Visit (Day 27 - 38) | 
| Number of New-onset Medical Conditions (NOMC) | The number of new-onset medical conditions (NOMC) were recorded. NOMC were tabulated by overall and treatment related events. | Day 1 through the Final Study Visit (Day 27 - 38). | 
| Acceptability of Vaccination Methods | LARs were asked to state their preference for different methods of vaccine delivery, assuming that a vaccine patch were to be available in the next two years. LARs reported their preference for their child receiving 1) a vaccine by shot or nasal spray given by a healthcare worker, 2) a vaccine patch given by a healthcare worker, 3) a vaccine patch given by the LAR but monitored by a healthcare worker, or 4) a vaccine patch given by the LAR at home. LARs rated their preference on a scale from 0 (definitely not) to 10 (definitely so). | Final Visit (Day 27 - 38) | 
| Overall Experience | LARs were asked to report their overall experience with the study so far at each study visit related to Patch 1. Experiences were rated on a scale from 1 to 5 where 1 = very negative and 5 = very positive. | Day 1, Day 2, Day 8, Final Visit (Day 27-38) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Reactogenicity, Acceptability, Microneedle patch