Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema (RAPIDe-3)

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

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.

Study Overview

• Status: Recruiting
• 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
• Intervention / Treatment: Drug: Deucrictibant, Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pharvaris Clinical Team; Phone Number: +31 (71) 203-6410; Email: clinicaltrials@pharvaris.com

Study Locations

• United States
  • Arizona
    • Paradise Valley, Arizona, United States, 85258
      • Recruiting
      • Study Site
  • California
    • Walnut Creek, California, United States, 94598
      • Recruiting
      • Study Site
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Recruiting
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Deucrictibant administered for first HAE attack, placebo administered for second HAE attack.	Drug: Deucrictibant, Placebo; Deucrictibant Soft Capsules for Oral Use
Experimental: Arm 2; Placebo administered for first HAE attack, deucrictibant administered for second HAE attack.	Drug: Deucrictibant, Placebo; Deucrictibant Soft Capsules for Oral Use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.	Pre-treatment to 12 hours post-treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of study drug-treated attacks achieving PGI-C rating of at least "a little better" at 4 hours post-treatment.	The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.	Pre-treatment to 4 hours post-treatment.
Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment.	The PGI-C (7-point scale) is used to evaluate the change in the HAE attack symptoms as compared to pre-treatment.	Pre-treatment to 12 hours post-treatment.
Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S).	Defined as achieving ≥1 point reduction in PGI-S (5-point scale) from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment.	Pre-treatment to 12 hours post-treatment.
Time to complete symptom resolution, defined as achieving PGI-S rating of "none" within 48 hours post-treatment.	The PGI-S (5-point scale) is used to evaluate the severity of HAE attack symptoms.	Pre-treatment to 48 hours post-treatment.
Time to End of Progression (EoP) in attack symptoms within 12 hours.	EoP time defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved.	Pre-treatment to 12 hours post-treatment.
Proportion of study drug-treated attacks requiring rescue medication within 24 hours post-treatment.	Rescue medication is defined as the participant's usual acute on-demand HAE treatment taken if symptoms persist or progress after study drug administration.	Pre-treatment to 24 hours post-treatment.
Proportion of attacks achieving symptom resolution.	Defined as achieving PGI-S rating of "none" with one dose of study drug at 24 hours post-treatment.	Pre-treatment to 24 hours post-treatment.
Time to substantial symptom relief by Angioedema Symptom Rating Scale (AMRA).	Defined as a ≥50% reduction in AMRA composite score from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment.	Pre-treatment to 12 hours post-treatment.
Time to almost complete or complete symptom relief by AMRA.	Defined as all item scores in AMRA having a value ≤10 for 2 consecutive timepoints within 24 hours post-treatment.	Pre-treatment to 24 hours post-treatment.
Proportion of study drug-treated attacks reaching almost complete or complete symptom relief by AMRA.	Defined as all item scores in AMRA having a value ≤10 at 24 hours post-treatment.	Pre-treatment to 24 hours post-treatment.
Time to EoP in attack symptoms within 12 hours.	Defined as the earliest post-treatment timepoint after which every individual AMRA item is stable or improved at all subsequent timepoints.	Pre-treatment to 12 hours post-treatment.

Collaborators and Investigators

• Sponsor: Pharvaris Netherlands B.V.
• Investigators: Study Director: Study Director, Pharvaris, Pharvaris Netherlands B.V.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: March 18, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHVS416; PHA121; On-Demand; Deucrictibant; Pharvaris
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
• Other Study ID Numbers: PHA022121-C306

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No