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This is a Phase 2a study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of ATI-450 vs placebo in patients with moderate to severe Hidradenitis Suppurativa (HS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATI-450 | Experimental | ATI-450 50 milligrams (mg) oral tablet twice daily (BID) |
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| Placebo | Experimental | Placebo oral tablet BID |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATI-450 | Drug | Oral, small molecule MK2 inhibitor |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Abscess and Inflammatory Nodule (AN) Count at Week 12 | AN count was the sum of number of abscess and inflammatory nodules across anatomical regions. The least square (LS) mean change from baseline in the count at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model. | Baseline, Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 12 | HiSCR50 Achiever was defined as a participant having a ≥50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase in the number of abscesses, and no increase in the number of draining fistula counts from baseline. A participant was considered an achiever only if all 3 criteria mentioned above were fulfilled. Model-based estimates and 90% confidence intervals (CIs) were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline count of inflammatory abscesses and nodules was used. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajay Aggarwal | Aclaris Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aclaris Investigational Site | Birmingham | Alabama | 35244 | United States | ||
| Aclaris Investigational Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | ATI-450 | Participants received a single oral tablet of ATI-450 50 milligrams (mg) twice daily (BID) for 12 weeks. |
| FG001 | Placebo | Participants received a single oral tablet of Placebo BID for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 4, 2022 | Jul 3, 2024 |
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Randomized, double-blind, placebo-controlled study
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The blinded placebo drug is packaged to match the active study drug and will be stored under the same conditions.
| Placebo oral tablet | Drug | Placebo tablet manufactured to match ATI-450 in appearance |
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| Week 12 |
| Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS-4) at Week 12 | The IHS-4 is a validated tool used to access the HS severity and is calculated based on the clinical signs of HS: inflammatory nodules, abscesses and draining tunnels (fistulas and sinuses). The IHS-4 score = (number of nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels [fistulas/sinuses] multiplied by 4). Mild HS is a score of 3 or less, moderate HS is a score of 4-10, and severe HS is a score of 11 or higher. A decrease in score means less severity. | Baseline, Week 12 |
| Percentage of Participants Achieving NRS30 | NRS30 Achiever was defined as participants achieving at least a 30% reduction from baseline in Patient's Global Assessment of Skin Pain (PGA-SP) and at least 1 unit reduction from baseline in PGA-SP at Week 12 among participants with baseline PGA-SP ≥3. Model-based estimates and 90% CIs were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline PGA-SP was used. | Week 12 |
| Change From Baseline in Hidradenitis Suppurativa-Physician Global Assessment (HSPGA) at Week 12 | In the HS-PGA scale, the Investigators rated the counts of nodules (inflammatory and non-inflammatory) abscesses and fistulas (both draining and nondraining) and assigned a participant to 1 of 6 categories ranging from clear (0) to very severe (5). A decrease in score means a better outcome. | Baseline, Week 12 |
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12 | The DLQI is a 10-item validated questionnaire used to assess the impact of HS disease symptoms and treatment on quality of life (QoL). It consists of questions including a single "yes/no" question and questions with possible responses of "not at all," "a little," "a lot," or "very much." These questions evaluate the impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each question was scored using a 4-point scale ranging from 0 to 3 based on a participant's response: not at all/not relevant (0), a little (1), a lot (2) and very much (3). The total score of the DLQI ranged from 0 to 30 and was calculated by adding up the scores from each question. The higher the score, the greater the impact on a participant's QoL. | Baseline, Week 12 |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs are defined as AEs with an onset date on or after the date of first administration of study drug and before the date of last administration of study drug + 30 days. A summary of non-serious AEs and serious AEs, regardless of causality is located in Reported AEs section. | Baseline through Day 115 |
| ATI-450 and Metabolite (CDD-2164) Concentrations | 2 hours postdose on Days 1, 8, and 85 |
| Fort Smith |
| Arkansas |
| 72916 |
| United States |
| Aclaris Investigational Site | Encino | California | 91436 | United States |
| Aclaris Investigational Site | San Francisco | California | 94115 | United States |
| Aclaris Investigational Site | Thousand Oaks | California | 91436 | United States |
| Aclaris Investigational Site | Boca Raton | Florida | 33486 | United States |
| Aclaris Investigational Site | Hollywood | Florida | 33021 | United States |
| Aclaris Investigational Site | Tampa | Florida | 33613 | United States |
| Aclaris Investigational Site | Marietta | Georgia | 30060 | United States |
| Aclaris Investigational Site | Sandy Springs | Georgia | 30328 | United States |
| Aclaris Investigational Site | Metairie | Louisiana | 70006 | United States |
| Aclaris Investigational Site | Fort Gratiot | Michigan | 48059 | United States |
| Aclaris Investigational Site | Charlotte | North Carolina | 28277 | United States |
| Aclaris Investigational Site | Athens | Ohio | 45701 | United States |
| Aclaris Investigational Site | Mason | Ohio | 45040 | United States |
| Aclaris Investigational Site | Hershey | Pennsylvania | 17033 | United States |
| Aclaris Investigational Site | Anderson | South Carolina | 29621 | United States |
| Aclaris Investigational Site | Nashville | Tennessee | 37215 | United States |
| Aclaris Investigational Site | Houston | Texas | 77054 | United States |
| Aclaris Investigational Site | Sugar Land | Texas | 77478 | United States |
| Received at Least 1 Dose of Study Drug |
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| COMPLETED |
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| NOT COMPLETED |
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Full analysis set (FAS) population included all participants who have been randomized and administered at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | ATI-450 | Participants received a single oral tablet of ATI-450 50 mg BID for 12 weeks. |
| BG001 | Placebo | Participants received a single oral tablet of Placebo BID for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Abscess and Inflammatory Nodule (AN) Count at Week 12 | AN count was the sum of number of abscess and inflammatory nodules across anatomical regions. The least square (LS) mean change from baseline in the count at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model. | FAS population: All participants who were randomized and administered at least 1 dose of study drug. | Posted | Least Squares Mean | 90% Confidence Interval | AN count | Baseline, Week 12 |
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| Secondary | Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) at Week 12 | HiSCR50 Achiever was defined as a participant having a ≥50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase in the number of abscesses, and no increase in the number of draining fistula counts from baseline. A participant was considered an achiever only if all 3 criteria mentioned above were fulfilled. Model-based estimates and 90% confidence intervals (CIs) were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline count of inflammatory abscesses and nodules was used. | FAS population: All participants who were randomized and administered at least 1 dose of study drug. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Change From Baseline in International Hidradenitis Suppurativa Severity Score System (IHS-4) at Week 12 | The IHS-4 is a validated tool used to access the HS severity and is calculated based on the clinical signs of HS: inflammatory nodules, abscesses and draining tunnels (fistulas and sinuses). The IHS-4 score = (number of nodules multiplied by 1) + (number of abscesses multiplied by 2) + (number of draining tunnels [fistulas/sinuses] multiplied by 4). Mild HS is a score of 3 or less, moderate HS is a score of 4-10, and severe HS is a score of 11 or higher. A decrease in score means less severity. | FAS population: All participants who were randomized and administered at least 1 dose of study drug. | Posted | Least Squares Mean | 90% Confidence Interval | units on a scale | Baseline, Week 12 |
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| Secondary | Percentage of Participants Achieving NRS30 | NRS30 Achiever was defined as participants achieving at least a 30% reduction from baseline in Patient's Global Assessment of Skin Pain (PGA-SP) and at least 1 unit reduction from baseline in PGA-SP at Week 12 among participants with baseline PGA-SP ≥3. Model-based estimates and 90% CIs were produced. Firth's penalized likelihood logistic regression model with fixed effects for treatment and baseline PGA-SP was used. | Only participants in the FAS population with a baseline NRS-PGA -SP ≥3 were evaluated for this outcome measure. | Posted | Number | 90% Confidence Interval | percentage of participants | Week 12 |
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| Secondary | Change From Baseline in Hidradenitis Suppurativa-Physician Global Assessment (HSPGA) at Week 12 | In the HS-PGA scale, the Investigators rated the counts of nodules (inflammatory and non-inflammatory) abscesses and fistulas (both draining and nondraining) and assigned a participant to 1 of 6 categories ranging from clear (0) to very severe (5). A decrease in score means a better outcome. | FAS population: All participants who were randomized and administered at least 1 dose of study drug. | Posted | Least Squares Mean | 90% Confidence Interval | units on a scale | Baseline, Week 12 |
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| Secondary | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12 | The DLQI is a 10-item validated questionnaire used to assess the impact of HS disease symptoms and treatment on quality of life (QoL). It consists of questions including a single "yes/no" question and questions with possible responses of "not at all," "a little," "a lot," or "very much." These questions evaluate the impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each question was scored using a 4-point scale ranging from 0 to 3 based on a participant's response: not at all/not relevant (0), a little (1), a lot (2) and very much (3). The total score of the DLQI ranged from 0 to 30 and was calculated by adding up the scores from each question. The higher the score, the greater the impact on a participant's QoL. | FAS population: All participants who were randomized and administered at least 1 dose of study drug. | Posted | Least Squares Mean | 90% Confidence Interval | units on a scale | Baseline, Week 12 |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAEs are defined as AEs with an onset date on or after the date of first administration of study drug and before the date of last administration of study drug + 30 days. A summary of non-serious AEs and serious AEs, regardless of causality is located in Reported AEs section. | Safety population: All participants randomly assigned to study drug and who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline through Day 115 |
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| Secondary | ATI-450 and Metabolite (CDD-2164) Concentrations | Pharmacokinetic (PK) population: All participants who were randomized, took at least 1 dose of study drug, and had at least 1 evaluable PK assay. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | Nanograms per milliliter (ng/ml) | 2 hours postdose on Days 1, 8, and 85 |
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Baseline through Day 115
Safety population: All participants randomly assigned to study drug and who received at least 1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ATI-450 | Participants received a single oral tablet of ATI-450 50 mg BID for 12 weeks. | 0 | 48 | 0 | 48 | 23 | 48 |
| EG001 | Placebo | Participants received a single oral tablet of Placebo BID for 12 weeks. | 0 | 47 | 1 | 47 | 13 | 47 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hidradenitis | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 24.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operations | Aclaris Therapeutics, Inc. | 1-833-225-2747 | clinicaloperations@aclaristx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 16, 2023 | Apr 9, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D017497 | Hidradenitis Suppurativa |
| D016575 | Hidradenitis |
| ID | Term |
|---|---|
| D017192 | Skin Diseases, Bacterial |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012874 | Skin Diseases, Infectious |
| D013492 | Suppuration |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D013543 | Sweat Gland Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Units | Counts |
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| Participants |
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