C1 Esterase Inhibitor Deficiency, C1 Inhibitor Deficiency, Hereditary Angioedema, Hereditary Angioedema Attack, Hereditary Angioedema - Type 1, Hereditary Angioedema - Type 2, Hereditary Angioedema Type I, Hereditary Angioedema Type II, Hereditary Angioedema Types I and II, Hereditary Angioedema With C1 Esterase Inhibitor Deficiency
Conditions
Keywords
HAE, HAE Type I, HAE Type II, Oral Treatment, Bradykinin B2 Receptor Antagonists, PHVS416, PHA121, PHA-022121, Deucrictibant
Brief summary
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.
Detailed description
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).
Interventions
DRUGDeucrictibant
deucrictibant soft capsules for oral use
DRUGPlacebo
Matching placebo capsules for oral use
Sponsors
Pharvaris Netherlands B.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment | Assessed 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3) | Assessed from pre-treatment to 48 hours post-treatment | 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 to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score | Assessed from pre-treatment to 48 hours post-treatment | Time to a ≥50% reduction in VAS-3 composite score from the pre-treatment score. |
| Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment | Pre-treatment and 4 hours post-treatment | MSCS scores range between 0 and 3. A higher score means a worse outcome. |
| Treatment Outcome Score (TOS) at 4 Hours Post-treatment | 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 to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom | Within 48 hours post-treatment | Time to onset of primary symptom relief assessed by a 30% reduction in the VAS for the primary symptom within 48 hours post-treatment |
| Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours. | Assessed at 12 hours post study drug treatment | Proportion of blinded study drug treated attacks requiring HAE rescue medication within 12 hours post-treatment. |
| Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment | Assessed at 48 hours post study drug treatment | The proportion of treated attacks with first use of HAE rescue medication within 48 hours post-treatment with PHA-022121. |
| Time to Change in the VAS Score for Skin Pain Score - 30% Reduction | Within 48 hours post treatment | 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. |
| Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment | 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 to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score | Assessed from pre-treatment to 48-hours post-treatment | VAS-3 scores range between 0 and 100. |
| Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score | 48 hours post-treatment | 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 to Onset of Primary Symptom Relief by 50% Reduction in VAS Score | Within 48 hours post-treatment | 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. |
| Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Assessed at 24 hours post-study drug treatment | Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced. |
| Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Assessed at 48 hours post-study drug treatment | Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 hours has been experienced. |
| Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score | 48 hours post-treatment | 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. |
| Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score | 48 hours post-treatment | 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 to Change in the VAS Score for Skin Swelling Score - 30% Reduction | Within 48 hours post-treatment | 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 to Change in the VAS Score for Abdominal Pain Score - 30% Reduction | Within 48 hours post-treatment | 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. |
| TOS at 24 Hours Post-treatment | Assessed within 24 hours post treatment | Treatment outcome score at 24 hours post-treatment. A higher score indicates improvement. |
Countries
Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 89 patients were screened, of which 74 patients were enrolled and randomized to the 3 PHA-022121 cohorts as follows: 25 participants to the 30 mg cohort, 25 participants to the 20 mg cohort, and 24 participants to the 10 mg cohort. From Part I to Part II, participants remained at their randomly assigned dose level. The majority of screen failures were due to inclusion criterion not met.
Pre-assignment details
In Part I, participants in a quiescent state received a single dose of PHA-022121 at the assigned dose (10, 20, or 30 mg) to assess PK and safety. In Part II, participants received 2 single doses of PHA-022121 (10, 20, or 30 mg) and one single dose of placebo to assess efficacy and safety. Each participant administered their randomly assigned dose (either 10, 20, or 30 mg) for each of the 3 qualifying HAE attacks according to 1 of the 3 randomly assigned treatment sequences (crossover design).
Participants by arm
| Arm | Count |
|---|---|
| PHA-022121 Low Dose - 10 mg Part I: Single low dose of PHA-022121 (10 mg), non-attack state. | 24 |
| PHA-022121 Medium Dose - 20 mg Part I: Single medium dose of PHA-022121 (20 mg), non-attack state. | 25 |
| PHA-022121 High Dose - 30 mg Part I: Single high dose of PHA-022121 (30 mg), non-attack state. | 25 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part II (Self-administration, Efficacy) | Participants Met Primary Analysis Criteria | 6 | 9 | 8 |
| Part II (Self-administration, Efficacy) | Withdrawal by Subject | 2 | 3 | 5 |
| Part I (Non-Attack, Safety) | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PHA-022121 Medium Dose - 20 mg | PHA-022121 High Dose - 30 mg | Total | PHA-022121 Low Dose - 10 mg |
|---|---|---|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 13.89 | 41.4 years STANDARD_DEVIATION 15.38 | 43.3 years STANDARD_DEVIATION 14.41 | 42.9 years STANDARD_DEVIATION 14.15 |
| Age, Customized Adults (18-64 years) | 24 Participants | 23 Participants | 69 Participants | 22 Participants |
| Age, Customized From 65-84 years | 1 Participants | 2 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 0 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 22 Participants | 24 Participants | 64 Participants | 18 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 1 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 25 Participants | 71 Participants | 22 Participants |
| Sex: Female, Male Female | 17 Participants | 15 Participants | 49 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 25 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 | 0 / 25 | 0 / 38 | 0 / 29 | 0 / 36 | 0 / 21 | 0 / 16 | 0 / 22 | 0 / 53 |
| other Total, other adverse events | 2 / 23 | 2 / 24 | 4 / 25 | 3 / 38 | 1 / 29 | 2 / 36 | 3 / 21 | 1 / 16 | 2 / 22 | 4 / 53 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 | 0 / 25 | 0 / 38 | 0 / 29 | 0 / 36 | 0 / 21 | 0 / 16 | 0 / 22 | 0 / 53 |
Outcome results
Primary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment | -14.83 Score on a scale | Standard Error 1.833 |
| PHA-022121 Medium Dose - 20 mg | Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment | -13.10 Score on a scale | Standard Error 2.111 |
| PHA-022121 High Dose - 30 mg | Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment | -14.37 Score on a scale | Standard Error 1.975 |
| Placebo | Change of the 3-symptom Composite Visual Analogue Scale (VAS-3) Score From Pre-treatment to 4 Hours Post-treatment | 1.92 Score on a scale | Standard Error 1.596 |
p-value: <0.000195% CI: [-21.52, -11.97]Mixed model repeated measures
p-value: <0.000195% CI: [-20.22, -9.81]Mixed model repeated measures
p-value: <0.000195% CI: [-21.27, -11.29]Mixed model repeated measures
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment | -1.65 Score on a scale | Standard Error 0.117 |
| PHA-022121 Medium Dose - 20 mg | Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment | -1.50 Score on a scale | Standard Error 0.123 |
| PHA-022121 High Dose - 30 mg | Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment | -1.68 Score on a scale | Standard Error 0.122 |
| Placebo | Change in Mean Symptom Complex Severity Score From Pre-treatment to 24 Hours Post-treatment | -1.20 Score on a scale | Standard Error 0.163 |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment | -1.08 Score on a scale |
| PHA-022121 Medium Dose - 20 mg | Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment | -0.91 Score on a scale |
| PHA-022121 High Dose - 30 mg | Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment | -0.68 Score on a scale |
| Placebo | Change in the Mean Symptom Complex Severity (MSCS) Score From Pre-treatment to 4 Hours Post-treatment | -0.29 Score on a scale |
p-value: <0.000195% CI: [-1.11, -0.46]Mixed model repeated measures
p-value: 0.000895% CI: [-0.97, -0.26]Mixed model repeated measures
p-value: 0.029195% CI: [-0.73, -0.04]Mixed model repeated measures
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours. | 7 Attacks requiring HAE rescue medication |
| PHA-022121 Medium Dose - 20 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours. | 3 Attacks requiring HAE rescue medication |
| PHA-022121 High Dose - 30 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours. | 2 Attacks requiring HAE rescue medication |
| Placebo | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 12 Hours. | 31 Attacks requiring HAE rescue medication |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks | 37 Attacks requiring HAE rescue medication |
| PHA-022121 Low Dose - 10 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks requiring HAE rescue medication | 9 Attacks requiring HAE rescue medication |
| PHA-022121 Medium Dose - 20 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks requiring HAE rescue medication | 3 Attacks requiring HAE rescue medication |
| PHA-022121 Medium Dose - 20 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks | 28 Attacks requiring HAE rescue medication |
| PHA-022121 High Dose - 30 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks | 31 Attacks requiring HAE rescue medication |
| PHA-022121 High Dose - 30 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks requiring HAE rescue medication | 4 Attacks requiring HAE rescue medication |
| Placebo | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks | 51 Attacks requiring HAE rescue medication |
| Placebo | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 24 Hours. | Number of treated attacks requiring HAE rescue medication | 37 Attacks requiring HAE rescue medication |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks | 37 Attacks requiring HAE rescue medication |
| PHA-022121 Low Dose - 10 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks requiring HAE rescue medication | 9 Attacks requiring HAE rescue medication |
| PHA-022121 Medium Dose - 20 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks requiring HAE rescue medication | 4 Attacks requiring HAE rescue medication |
| PHA-022121 Medium Dose - 20 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks | 28 Attacks requiring HAE rescue medication |
| PHA-022121 High Dose - 30 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks | 31 Attacks requiring HAE rescue medication |
| PHA-022121 High Dose - 30 mg | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks requiring HAE rescue medication | 5 Attacks requiring HAE rescue medication |
| Placebo | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks | 51 Attacks requiring HAE rescue medication |
| Placebo | Proportion of Study Drug Treated Attacks Requiring HAE Rescue Medication Within 48 Hours | Number of treated attacks requiring HAE rescue medication | 37 Attacks requiring HAE rescue medication |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score | 3.3 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score | 4.0 Hours |
| PHA-022121 High Dose - 30 mg | Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score | 4.0 Hours |
| Placebo | Time to a ≥50% Reduction in VAS-3 Composite Score From the Pre-treatment Score | 22.8 Hours |
p-value: <0.000195% CI: [2.41, 8.59]Marginal Cox Proportional Hazards Model
p-value: 0.000395% CI: [1.8, 7.38]Marginal Cox Proportional Hazards Model
p-value: <0.000195% CI: [2.26, 6.63]Marginal Cox Proportional Hazards Model
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction | 1.9 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction | 1.4 Hours |
| PHA-022121 High Dose - 30 mg | Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction | 2.9 Hours |
| Placebo | Time to Change in the VAS Score for Abdominal Pain Score - 30% Reduction | 20.0 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Change in the VAS Score for Skin Pain Score - 30% Reduction | 2.9 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Change in the VAS Score for Skin Pain Score - 30% Reduction | 3.4 Hours |
| PHA-022121 High Dose - 30 mg | Time to Change in the VAS Score for Skin Pain Score - 30% Reduction | 2.7 Hours |
| Placebo | Time to Change in the VAS Score for Skin Pain Score - 30% Reduction | 22.8 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction | 2.5 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction | 3.5 Hours |
| PHA-022121 High Dose - 30 mg | Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction | 3.8 Hours |
| Placebo | Time to Change in the VAS Score for Skin Swelling Score - 30% Reduction | 23.3 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point. Medians are as follows: Low Dose 10 mg - NA (
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment | NA Hours |
| PHA-022121 Medium Dose - 20 mg | Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment | NA Hours |
| PHA-022121 High Dose - 30 mg | Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment | NA Hours |
| Placebo | Time to First HAE Rescue Medication Use for Study Drug-treated Attacks Within 48 Hours Post-treatment | 6.0 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3) | 5.8 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3) | 20.0 Hours |
| PHA-022121 High Dose - 30 mg | Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3) | 20.0 Hours |
| Placebo | Time to Onset of Almost Complete or Complete Symptom Relief by Visual Analogue Scale (VAS-3) | 42.0 Hours |
p-value: 0.000195% CI: [1.61, 4.38]Marginal Cox Proportional Hazards Model
p-value: <0.000195% CI: [2.81, 9.22]Cox Proportional Hazards Model
p-value: 0.012795% CI: [1.19, 4.27]Marginal Cox Proportional Hazards Model
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom | 2.0 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom | 3.0 Hours |
| PHA-022121 High Dose - 30 mg | Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom | 2.9 Hours |
| Placebo | Time to Onset of Primary Symptom Relief Assessed by a 30% Reduction in the VAS for the Primary Symptom | 23.3 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score | 2.9 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score | 4.5 Hours |
| PHA-022121 High Dose - 30 mg | Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score | 4.0 Hours |
| Placebo | Time to Onset of Primary Symptom Relief by 50% Reduction in VAS Score | 22.8 Hours |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score | 2.1 Hours |
| PHA-022121 Medium Dose - 20 mg | Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score | 2.7 Hours |
| PHA-022121 High Dose - 30 mg | Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score | 2.5 Hours |
| Placebo | Time to Onset of Symptom Relief by ≥30% Reduction in Visual Analogue Scale (VAS-3) Composite Score From the Pre-treatment Score | 8.0 Hours |
p-value: <0.000195% CI: [2.01, 7.2]Marginal Cox Proportional Hazards Model
p-value: 0.002195% CI: [1.5, 6.3]Marginal Cox Proportional Hazards Model
p-value: <0.000195% CI: [2.1, 6.19]Marginal Cox Proportional Hazards Model
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | TOS at 24 Hours Post-treatment | 94.44 Score on a scale | Standard Deviation 21.183 |
| PHA-022121 Medium Dose - 20 mg | TOS at 24 Hours Post-treatment | 93.60 Score on a scale | Standard Deviation 21.19 |
| PHA-022121 High Dose - 30 mg | TOS at 24 Hours Post-treatment | 94.44 Score on a scale | Standard Deviation 16.013 |
| Placebo | TOS at 24 Hours Post-treatment | 76.92 Score on a scale | Standard Deviation 38.813 |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PHA-022121 Low Dose - 10 mg | Treatment Outcome Score (TOS) at 4 Hours Post-treatment | 60.52 Score on a scale |
| PHA-022121 Medium Dose - 20 mg | Treatment Outcome Score (TOS) at 4 Hours Post-treatment | 59.08 Score on a scale |
| PHA-022121 High Dose - 30 mg | Treatment Outcome Score (TOS) at 4 Hours Post-treatment | 67.44 Score on a scale |
| Placebo | Treatment Outcome Score (TOS) at 4 Hours Post-treatment | -3.62 Score on a scale |
p-value: <0.000195% CI: [40.35, 87.91]Mixed model repeated measures
p-value: <0.000195% CI: [36.71, 88.67]Mixed model repeated measures
p-value: <0.000195% CI: [46.09, 96.03]Mixed model repeated measures
Secondary
Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience 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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score | 80.56 Score on a scale | Standard Deviation 16.569 |
| PHA-022121 Medium Dose - 20 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score | 83.08 Score on a scale | Standard Deviation 23.096 |
| PHA-022121 High Dose - 30 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score | 77.55 Score on a scale | Standard Deviation 20.229 |
| Placebo | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Convenience Domain Score | 76.07 Score on a scale | Standard Deviation 27.441 |
Secondary
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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score | 79.17 Score on a scale | Standard Deviation 23.179 |
| PHA-022121 Medium Dose - 20 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score | 70.45 Score on a scale | Standard Deviation 30.29 |
| PHA-022121 High Dose - 30 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score | 72.92 Score on a scale | Standard Deviation 23.085 |
| Placebo | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Effectiveness Domain Score | 65.38 Score on a scale | Standard Deviation 23.532 |
Secondary
Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction 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
Population: Part I efficacy data not collected, consistent with and pre-specified in the study protocol. Includes all participants with evaluable data who completed the relevant assessment time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PHA-022121 Low Dose - 10 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score | 82.50 Score on a scale | Standard Deviation 18.907 |
| PHA-022121 Medium Dose - 20 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score | 80.68 Score on a scale | Standard Deviation 29.702 |
| PHA-022121 High Dose - 30 mg | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score | 76.74 Score on a scale | Standard Deviation 22.113 |
| Placebo | Treatment Satisfaction Questionnaire for Medication Scores at 48 Hours Post-treatment - Satisfaction Domain Score | 64.10 Score on a scale | Standard Deviation 24.623 |