## Protocol Section
### Identification Module
**NCT ID:** NCT06343779

**Acronym:** RAPIDe-3

**Brief Title:** Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema

**Official Title:** A Phase 3, Randomized, Double-blind, Placebo-controlled, Cross-over Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Attacks in Adolescents and Adults With Hereditary Angioedema

#### Organization Study ID Info
**ID:** PHA022121-C306
#### Organization
**Class:** INDUSTRY
**Full Name:** Pharvaris Netherlands B.V.
### Status Module
#### Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-02

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-30

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-26

**Type:** ACTUAL

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-04-03
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-18
**Study First Submit QC Date:** 2024-03-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Pharvaris Netherlands B.V.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-period, 2-treatment cross-over study to evaluate the efficacy and safety of orally administered deucrictibant compared to placebo for the on-demand treatment of HAE attacks, including non-severe laryngeal attacks, in participants ≥12 to ≤75 years of age with HAE type 1 or type 2 (HAE-1/2), a proportion of whom are using long-term prophylactic medication for HAE.

**Detailed Description:** The study consists of a Screening Phase during which eligibility is confirmed, a Treatment Phase in which participants will be randomized and receive double blinded study drug to treat 2 qualifying HAE attacks (i.e., 2 Treatment Periods within the Treatment Phase), and an End-of-Study Follow-up Phase after the second attack treated with study drug. In addition, for adolescent participants (age ≥12 to \<18 years), PK samples are collected after administration of deucrictibant at Day 1 in a non-attack state.

### Conditions Module

**Conditions:**

- Hereditary Angioedema

- Hereditary Angioedema Type I

- Hereditary Angioedema Type II

- Hereditary Angioedema Types I and II

- Hereditary Angioedema Attack

- Hereditary Angioedema With C1 Esterase Inhibitor Deficiency

- Hereditary Angioedema - Type 1

- Hereditary Angioedema - Type 2

- C1 Esterase Inhibitor [C1-INH] Deficiency

- C1 Esterase Inhibitor Deficiency

- C1 Esterase Inhibitor, Deficiency of

- C1 Inhibitor Deficiency

**Keywords:**

- HAE

- HAE Type I

- HAE Type II

- Oral Treatment

- Bradykinin B2 Receptor Antagonists

- PHVS416

- PHA121

- On-Demand

- Deucrictibant

- Pharvaris

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 120

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Deucrictibant administered for first HAE attack, placebo administered for second HAE attack.

**Intervention Names:**

- Drug: Deucrictibant, Placebo

**Label:** Arm 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Placebo administered for first HAE attack, deucrictibant administered for second HAE attack.

**Intervention Names:**

- Drug: Deucrictibant, Placebo

**Label:** Arm 2

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm 1

- Arm 2

**Description:** Deucrictibant Soft Capsules for Oral Use

**Name:** Deucrictibant, Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.

**Measure:** Time to onset of symptom relief, defined as Patient Global Impression of Change (PGI-C) rating of at least "a little better" for 2 consecutive timepoints within 12 hours post-treatment.

**Time Frame:** Pre-treatment to 12 hours post-treatment.

#### Secondary Outcomes

**Description:** The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.

**Measure:** Proportion of study drug-treated attacks achieving PGI-C rating of at least "a little better" at 4 hours post-treatment.

**Time Frame:** Pre-treatment to 4 hours post-treatment.

**Description:** The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.

**Measure:** Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment.

**Time Frame:** Pre-treatment to 12 hours post-treatment.

**Description:** Defined as achieving ≥1 point reduction in PGI-S (5-point scale) from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment.

**Measure:** Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S).

**Time Frame:** Pre-treatment to 12 hours post-treatment.

**Description:** The PGI-S (5-point scale) is used to evaluate the severity of HAE attack symptoms.

**Measure:** Time to complete symptom resolution, defined as achieving PGI-S rating of "none" within 48 hours post-treatment.

**Time Frame:** Pre-treatment to 48 hours post-treatment.

**Description:** EoP time defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved.

**Measure:** Time to End of Progression (EoP) in attack symptoms within 12 hours.

**Time Frame:** Pre-treatment to 12 hours post-treatment.

**Description:** Rescue medication is defined as the participant's usual acute on-demand HAE treatment taken if symptoms persist or progress after study drug administration.

**Measure:** Proportion of study drug-treated attacks requiring rescue medication within 24 hours post-treatment.

**Time Frame:** Pre-treatment to 24 hours post-treatment.

**Description:** Defined as achieving PGI-S rating of "none" with one dose of study drug at 24 hours post-treatment.

**Measure:** Proportion of attacks achieving symptom resolution.

**Time Frame:** Pre-treatment to 24 hours post-treatment.

**Description:** Defined as a ≥50% reduction in AMRA composite score from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment.

**Measure:** Time to substantial symptom relief by Angioedema Symptom Rating Scale (AMRA).

**Time Frame:** Pre-treatment to 12 hours post-treatment.

**Description:** Defined as all item scores in AMRA having a value ≤10 for 2 consecutive timepoints within 24 hours post-treatment.

**Measure:** Time to almost complete or complete symptom relief by AMRA.

**Time Frame:** Pre-treatment to 24 hours post-treatment.

**Description:** Defined as all item scores in AMRA having a value ≤10 at 24 hours post-treatment.

**Measure:** Proportion of study drug-treated attacks reaching almost complete or complete symptom relief by AMRA.

**Time Frame:** Pre-treatment to 24 hours post-treatment.

**Description:** Defined as the earliest post-treatment timepoint after which every individual AMRA item is stable or improved at all subsequent timepoints.

**Measure:** Time to EoP in attack symptoms within 12 hours.

**Time Frame:** Pre-treatment to 12 hours post-treatment.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Provision of written informed consent/assent.
2. Male or female, aged ≥12 to ≤75 years at the time of providing written informed consent/assent.
3. Diagnosis of HAE-1/2.
4. History of at least 2 HAE attacks in the last 3 months before screening.
5. Experience with using standard-of-care treatment to effectively manage on-demand treatment for HAE attacks.
6. Participants on long-term prophylactic therapy with plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat, or lanadelumab) must be on a stable dose and regimen and intend to remain on the same dose for 6 months before screening and the duration of the study.
7. Capable of recording, without assistance, electronic HAE diary and ePRO data using an electronic device.
8. For adolescent participants aged ≥12 and \<18 years of age: body weight \>40 kg.
9. Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

Exclusion Criteria:

1. Any female who is pregnant, plans to become pregnant, or is breastfeeding.
2. Any diagnosis of angioedema other than HAE-1/2.
3. Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
4. Use of attenuated androgens for short-term prophylaxis within the last 30 days before the time of randomization.
5. Abnormal hepatic function.
6. Abnormal renal function (eGFR \<60 ml/min/1.73 m2).
7. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
8. Has received prior on-demand HAE treatment with deucrictibant.
9. Currently participating in any other investigational drug study or receiving other investigational treatment within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
10. Prior gene therapy for any indication at any time.
11. Use of concomitant medications that are strong inhibitors/inducers of CYP3A4 within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
12. Known hypersensitivity to study drug or any of the excipients of study drug.

**Maximum Age:** 75 Years

**Minimum Age:** 12 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** clinicaltrials@pharvaris.com

**Name:** Pharvaris Clinical Team

**Phone:** +31 (71) 203-6410

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Birmingham

**Country:** United States

**Facility:** Study Site

**State:** Alabama

**Status:** RECRUITING

**Zip:** 35209

**Location 2:**

**City:** Paradise Valley

**Country:** United States

**Facility:** Study Site

**State:** Arizona

**Status:** RECRUITING

**Zip:** 85258

**Location 3:**

**City:** Little Rock

**Country:** United States

**Facility:** Study Site

**State:** Arkansas

**Status:** RECRUITING

**Zip:** 72205

**Location 4:**

**City:** Santa Monica

**Country:** United States

**Facility:** Study Site

**State:** California

**Status:** RECRUITING

**Zip:** 90404

**Location 5:**

**City:** Walnut Creek

**Country:** United States

**Facility:** Study Site

**State:** California

**Status:** RECRUITING

**Zip:** 94598

**Location 6:**

**City:** Colorado Springs

**Country:** United States

**Facility:** Study Site

**State:** Colorado

**Status:** RECRUITING

**Zip:** 80907-6231

**Location 7:**

**City:** Chevy Chase

**Country:** United States

**Facility:** Study Site

**State:** Maryland

**Status:** RECRUITING

**Zip:** 20815

**Location 8:**

**City:** Dallas

**Country:** United States

**Facility:** Study Site

**State:** Texas

**Status:** RECRUITING

**Zip:** 75231

**Location 9:**

**City:** San Juan

**Country:** Puerto Rico

**Facility:** Study Site

**Status:** RECRUITING

**Zip:** 00918

#### Overall Officials

**Official 1:**

**Affiliation:** Pharvaris Netherlands B.V.

**Name:** Study Director, Pharvaris

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000014581

- Term: Urticaria

- ID: D000017445

- Term: Skin Diseases, Vascular

- ID: D000012871

- Term: Skin Diseases

- ID: D000006969

- Term: Hypersensitivity, Immediate

- ID: D000006967

- Term: Hypersensitivity

- ID: D000007154

- Term: Immune System Diseases

- ID: D000081208

- Term: Hereditary Complement Deficiency Diseases

- ID: D000081207

- Term: Primary Immunodeficiency Diseases

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000007153

- Term: Immunologic Deficiency Syndromes

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M4127

- Name: Angioedema

- Relevance: HIGH

- As Found: Angioedema

- ID: M27584

- Name: Angioedemas, Hereditary

- Relevance: HIGH

- As Found: C1 Esterase Inhibitor Deficiency

- ID: M28606

- Name: Hereditary Angioedema Types I and II

- Relevance: HIGH

- As Found: Hereditary Angioedema Type I

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17330

- Name: Urticaria

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19714

- Name: Skin Diseases, Vascular

- Relevance: LOW

- As Found: Unknown

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6879

- Name: Deficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2286

- Name: Hereditary Complement Deficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10199

- Name: Immunologic Deficiency Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M2285

- Name: Primary Immunodeficiency Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: T2734

- Name: Hereditary Angioedema

- Relevance: HIGH

- As Found: Hereditary Angioedema

- ID: T4202

- Name: Oculocerebral Syndrome With Hypopigmentation

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000799

- Term: Angioedema

- ID: D000054179

- Term: Angioedemas, Hereditary

- ID: D000056829

- Term: Hereditary Angioedema Types I and II

### Intervention Browse Module - Browse Branches

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M5197

- Name: Bradykinin

- Relevance: LOW

- As Found: Unknown

- ID: M10725

- Name: Kininogens

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
