Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

Pharvaris Netherlands B.V.74 enrolled

Overview

This study evaluates the efficacy of orally administered deucrictibant for the acute treatment of attacks in patients with hereditary angioedema (HAE). Eligible subjects are randomized to one of three single doses of deucrictibant and placebo. The study will compare symptom relief (skin pain, skin swelling, abdominal pain) during HAE attacks and safety of each dose of deucrictibant with placebo.

In Part I of the study, patients in non-attack state receive the assigned active single dose of deucrictibant at the study center to assess pharmacokinetics (the way the body absorbs, distributes, and gets rid of the drug) and safety. In Part II of the study, patients self-administer blinded study drug at home to treat three HAE attacks with deucrictibant or placebo (cross-over).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hereditary Angioedema Hereditary Angioedema Type I Hereditary Angioedema Type II

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Signed and dated informed consent form 2. Diagnosis of HAE type I or II 3. Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months prior to screening 4. Reliable access and experience to use standard of care acute attack medications Key Exclusion Criteria: 1. Pregnancy or breast-feeding 2. Clinically significant abnormal electrocardiogram 3. Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study 4. Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment 5. Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus 6. Abnormal hepatic function 7. Abnormal renal function 8. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse 9. History of documented severe hypersensitivity to any medicinal product 10. Participation in any other investigational drug study within defined period

Locations (36)

Study site

Birmingham, Alabama, United States

Study site

Paradise Valley, Arizona, United States

Study site

San Diego, California, United States

Study site

Santa Monica, California, United States

Study site

Walnut Creek, California, United States

Study site

Chevy Chase, Maryland, United States

Study site

St Louis, Missouri, United States

Study site

Hershey, Pennsylvania, United States

Study site

Sofia, Bulgaria

Study site

Edmonton, Alberta, Canada

...and 26 more locations

Outcomes

Primary Outcomes

Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment

The primary endpoint of the study was the change of the VAS-3 (3-symptom composite visual analogue scale) score from pre-treatment to 4 hours post-treatment. The VAS-3 was calculated as the mean of the VAS scores of the 3 major HAE symptoms: skin swelling, skin pain, and abdominal pain. The VAS scores of the 3 major HAE symptoms (skin swelling, skin pain, and abdominal pain) could range between 0 (No swelling/No pain) and 100 (Extreme swelling/Excruciating pain)

Time frame: Assessed from pre-treatment to 4 hours post-treatment

Secondary Outcomes

Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score

VAS-3 scores range between 0 and 100.

Time frame: Assessed from pre-treatment to 48-hours post-treatment

Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3)

VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value \< 10. Complete symptom relief is defined as all 3 individual VAS scores are of the VAS-3 having a value of 0.

Time frame: Assessed from pre-treatment to 48 hours post-treatment

Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score

Time to a ≥50% reduction in VAS-3 composite score from the pre-treatment score.

Time frame: Assessed from pre-treatment to 48 hours post-treatment

Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment

MSCS scores range between 0 and 3. A higher score means a worse outcome.

Time frame: Pre-treatment and 4 hours post-treatment

Treatment Outcome Score (TOS) at 4 Hours Post-treatment

TOS range between -100 and 100. A positive score indicates improvement, a score of 0 indicates no change, and a negative score indicates worsening compared to pre-treatment.

Time frame: 4 hours post-treatment

Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom

Time to onset of primary symptom relief assessed by a 30% reduction in the VAS for the primary symptom within 48 hours post-treatment

Time frame: Within 48 hours post-treatment

Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours.

Proportion of blinded study drug treated attacks requiring HAE rescue medication within 12 hours post-treatment.

Time frame: Assessed at 12 hours post study drug treatment

Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment

The proportion of treated attacks with first use of HAE rescue medication within 48 hours post-treatment with PHA-022121.

Time frame: Assessed at 48 hours post study drug treatment

Time to Change in the VAS Score for Skin Pain Score - 30% Reduction

Time to change in the VAS score for Skin Pain Score - 30% reduction within 48-hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Time frame: Within 48 hours post treatment

Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment

Change in the Mean Symptom Complex Severity (MSCS) score from pre-treatment to 24 hours post-treatment. A lower MSCS score indicates a better outcome.

Time frame: 24 hours post-treatment

TOS at 24 Hours Post-treatment

Treatment outcome score at 24 hours post-treatment. A higher score indicates improvement.

Time frame: Assessed within 24 hours post treatment

Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score

MMRM analysis of Treatment Satisfaction Questionnaire for Medication (TSQM) at 48 hours post-treatment. The 11-item TSQM (version II) evaluated participant treatment satisfaction with the medication for the following scales: effectiveness, side effects, convenience, and overall satisfaction Scale scores were transformed into scores ranging from 0 to 100 and could be used to calculate a total composite score, a higher score indicating greater satisfaction.

Time frame: 48 hours post-treatment

Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score

Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Time frame: Within 48 hours post-treatment

Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours.

Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced.

Time frame: Assessed at 24 hours post-study drug treatment

Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours

Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced.

Time frame: Assessed at 48 hours post-study drug treatment

Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score

Time frame: 48 hours post-treatment

Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score

Time frame: 48 hours post-treatment

Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction

Time to change in the VAS score for Skin Swelling Score - 30% reduction within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Time frame: Within 48 hours post-treatment

Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction

Time to change in the VAS score for Abdominal Pain Score - 30% reduction within 48 hours post-treatment. VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Time frame: Within 48 hours post-treatment

Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

Overview

Conditions

Interventions

Eligibility

Locations (36)

Outcomes

Primary Outcomes

Secondary Outcomes