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Business reasons.
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This is a multicenter, randomized, double-blind, placebo-controlled phase 1b/2a study designed to evaluate the safety of an investigational product called ATR-04, to reduce the severity of epidermal growth factor receptor inhibitor (EGFRI) associated papulopustular rash on the face. This study will be performed at 10-12 clinical sites, with potentially a virtual component. Approximately 60 eligible subjects will participate. A subject's participation in the study will be up to a maximum of 86 days (up to 28 days for Screening, 28 days of BID treatment, and a 30 day no treatment follow-up period).
The primary objective of this study is to evaluate the safety and tolerability of ATR-04 compared to placebo.
This is a multicenter, randomized, double-blind, placebo-controlled phase 1b/2a study designed to evaluate the safety of an investigational product called ATR-04 to reduce the severity of epidermal growth factor receptor inhibitor (EGFRI) associated papulopustular rash on the face. This study will be performed at 10-12 clinical sites, with potentially a virtual component. After informed consent is obtained, subjects will enter a screening period for up to 28 days to determine eligibility prior to randomization.
Approximately 60 eligible subjects, will be randomized to receive ATR-04 or a placebo, in a ratio of 1:1.
On Day 1, subjects will be instructed on study medication administration technique, the first application by the subject will be observed in person, via telehealth or via video connection and the subject will be monitored for adverse events (AEs) for at least 20 minutes.
Subjects will perform twice daily (BID) study assigned medication applications for 28 days. Subjects will have in person or virtual visits throughout the study. Subjects will return all study materials (i.e. diary cards, and study medication containers, swabs) either in person or via mail on Day 29 for their End of Treatment visit.
Beginning on Day 1, subjects will be assessed for safety. In addition, subjects' faces will be examined and assessed utilizing the Investigator Global Assessment (IGA) in person or via a virtual visit. Subjects will complete the Quality of Life (QoL) tool and standardized digital photographs will be taken.
A subject's participation in the study will be up to a maximum of 86 days (up to 28 days for Screening, 28 days of BID treatment, and a 30 day no treatment follow-up period).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATR-04 | Experimental | The intervention is an ointment that will be applied topically BID for 28 days. It will be supplied in small aluminum foil packets. Packets of study medication will be labeled with Subject Kit numbers to ensure the double-blind treatment. |
|
| Placebo | Placebo Comparator | Placebo ointment will be applied topically BID for 28 days. It will be supplied in small aluminum foil packets. Packets of study medication will be labeled with Subject Kit numbers to ensure the double-blind treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATR-04 | Drug | ATR-04 is a proprietary formulated product containing lyophilized SEΔΔΔ, a Staphylococcus epidermidis genetically modified to be auxotrophic to D-alanine as the active ingredient. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), incidence of abnormal laboratory values, abnormal physical exams and abnormal vital signs. | Safety and tolerability of ATR-04 compared to placebo as assessed by incidence and severity of Adverse Events (AEs), Serious Adverse Events (SAEs), laboratory values, physical exams and vital signs. | Through study completion, on average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of ATR-04 assessed by IGA. | Assess the efficacy of ATR-04 compared to placebo to mitigate the severity of EGFRI-associated skin effects as assessed by IGA. | Up to Day 29 |
| Proportion of Subjects with Moderate or Severe Rash |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Endpoint to Evaluate Change in EGFRI Skin Rash Microbiome | Evaluate the microbiome of EGFRI skin rashes as determined by shotgun sequencing. | Through study completion, on average of 1 year |
| Exploratory Endpoint to Evaluate the Change in Skin Microbiome Associated with EGFRI Therapy |
Inclusion Criteria:
Exclusion Criteria:
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| ID | Term |
|---|---|
| D012393 | Rosacea |
| ID | Term |
|---|---|
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| Placebo | Other | Placebo |
|
Difference in proportion of subjects with moderate or severe facial rash as assessed by IGA.
| Up to Day 29 |
| Difference in Subjects That Require Additional Therapies | Difference in number of subjects that require additional therapies for the facial rash, such as antibiotics or steroids for ATR-04 compared to placebo. | Up to Day 29 |
| Difference in Quality of Life (QoL) of Subjects | Difference in QoL of subjects on ATR-04 compared to placebo as assessed by FACT-EGFRI-18. Score ranges from 0-72, with higher scores indicating better outcomes. | Up to Day 58. |
| Difference in Number of Inflammatory Lesions | Difference in number of inflammatory lesions on face for subjects on ATR-04 compared to placebo. | Up to Day 29. |
| Difference in Proportion of Subjects That Stop/Decrease EGFRI Therapy | Difference in proportion of subjects that stop or decrease dose of EGFRI therapy. | Up to Day 29. |
Evaluate the change in skin microbiome associated with EGFRI therapy as determined by shotgun sequencing. |
| Through study completion, on average of 1 year |