Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II

NCT05047185 — Phase 2, Terminated, 34 participants, Pharvaris Netherlands B.V.

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

A Phase II, Double-blind, Placebo-controlled, Randomized, Dose-ranging, Parallel Group Study to Evaluate the Safety and Efficacy of PHA-022121 Administered Orally for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)

Registry	NCT05047185, acronym HAE CHAPTER-1
Status	Terminated - Sponsor decision. All remaining participants (21 total) were rolled over from Part 2 to study PHA022121-C307 (NCT06679881).
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: quadruple, prevention
Enrollment	34 (Actual)
Sponsor	Pharvaris Netherlands B.V. (Industry)
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 Deficiency, C1 Inhibitor Deficiency
Interventions	Deucrictibant low dose, Deucrictibant high dose, Placebo (Drug)
Dates	start 2022-04-19, primary completion 2025-06-30, completion 2025-06-30, first posted 2021-09-17, last updated 2026-08-17
Locations	19 sites in United States, Austria, Bulgaria, Canada, Germany, Ireland, Italy, Poland and 1 more countries

-Summary

This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

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+Arms and interventions

Arm	Type	Interventions	Description
Part 1: Low dose	Experimental	Drug: Deucrictibant low dose	BID low dose of deucrictibant
Part 1: High dose	Experimental	Drug: Deucrictibant high dose	BID high dose of deucrictibant
Part 1: Placebo	Placebo comparator	Drug: Placebo	BID placebo
Part 2: Open-label	Experimental	Drug: Deucrictibant high dose	BID high dose of deucrictibant

Deucrictibant low dose (Drug): Deucrictibant softgel capsules for oral use (PHVS416)
Deucrictibant high dose (Drug): Deucrictibant softgel capsules for oral use (PHVS416)
Placebo (Drug): Matching placebo capsules for oral use

+Outcome measures

Primary outcomes

Number of Investigator-confirmed Hereditary Angioedema (HAE) Attacks (Expressed as the Normalized Number of Attacks Per Month [4 Weeks] of Exposure) During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily electronic patient-reported outcome (ePRO) diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Mean rate ratio, confidence interval (CI), and p-value were estimated using a generalized linear model with Poisson distribution, with baseline attack rate included as a factor.

Secondary outcomes

Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28. Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability.
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1 [Up to Day 84]: Baseline attack rate was defined as each participant's normalized HAE attack rate (attacks per 4 weeks) prior to randomization, based on documented history or confirmed during screening. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Percent reduction from baseline was calculated for each participant by comparing the normalized treatment-period attack rate to the baseline attack rate. Participants were classified as responders if they achieved ≥50%, ≥70%, or ≥90% reduction in attack rate relative to baseline during Part 1.
Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Participants reporting no confirmed attacks over the treatment period were considered attack-free.
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Time to First Investigator-confirmed HAE Attack in the Treatment Period in Part 1 [Up to Day 84]: Time to first investigator-confirmed HAE attack was defined as days from date of first administration of study drug until the onset date of first Investigator-confirmed HAE attack. Participants without an Investigator-confirmed HAE attack during the treatment period in Part 1 were censored at the date of the last dose of study drug +1 in Part 1 or last day of the study, whichever came sooner.
Number of Investigator-confirmed HAE Attacks Resulting in a Visit to the Emergency Department or an Admission to Hospital During the Treatment Period in Part 1 [Up to Day 84]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. Only Investigator-confirmed attacks resulting in emergency department visits or hospital admissions were included.
Number of Investigator-confirmed HAE Attacks During the Treatment Period in Part 2 [Day 84 to Day 938]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. An attack will be counted as in Part 2 if it occurs after the first IMP administration in Part 2 and within 24 hours after last IMP administration in Part 2.
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 2 [Day 84 to Day 938]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28. Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability. LSM and SE were estimated using a generalized linear model with Poisson distribution.
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 2 [Day 84 to Day 938]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack. Attacks were recorded via daily ePRO diaries and confirmed by the investigator. Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28. LSM and SE were estimated using a generalized linear model with Poisson distribution.
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2 [Day 84 to Day 938]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2 [Day 84 to Day 938]: HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx). HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.

+Eligibility

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Signed and dated informed consent form
* Diagnosis of HAE type I or II
* Documented history of at least 3 HAE attacks within the last 3 consecutive months prior to screening, or a minimum of 2 HAE attacks during the screening period
* Reliable access and experience to use standard of care acute attack medications

Exclusion Criteria:

* Pregnancy or breast-feeding
* Clinically significant abnormal electrocardiogram
* Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
* Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrolment
* Abnormal hepatic function
* Abnormal renal function
* History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
* Participation in any other investigational drug study within defined period

+Posted results

Participant flow

Milestone	Part 1: Placebo	Part 1: Deucrictibant 10 mg BID	Part 1: Deucrictibant 20 mg BID
Started	11	11	12
Completed	9	11	10
Not completed	2	0	2

Outcome results

Number of Investigator-confirmed Hereditary Angioedema (HAE) Attacks (Expressed as the Normalized Number of Attacks Per Month [4 Weeks] of Exposure) During the Treatment Period in Part 1 (Primary), Least squares mean, attacks per month: Placebo 1.93 +/- 0.391; Deucrictibant 10 mg BID 0.40 +/- 0.170; Deucrictibant 20 mg BID 0.30 +/- 0.153 (p 0.0010)
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1 (Secondary), Least squares mean, attacks per month: Placebo 1.51 +/- 0.394; Deucrictibant 10 mg BID 0.26 +/- 0.150; Deucrictibant 20 mg BID 0.12 +/- 0.103
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1 (Secondary), Least squares mean, attacks per month: Placebo 1.40 +/- 0.337; Deucrictibant 10 mg BID 0.35 +/- 0.159; Deucrictibant 20 mg BID 0.10 +/- 0.089
Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1 (Secondary), Count of participants, Participants: Placebo 2; Deucrictibant 10 mg BID 9; Deucrictibant 20 mg BID 9
Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1 (Secondary), Count of participants, Participants: Placebo 0; Deucrictibant 10 mg BID 6; Deucrictibant 20 mg BID 4
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1 (Secondary), Mean, days: Placebo 13.6 +/- 9.69; Deucrictibant 10 mg BID 3.8 +/- 7.73; Deucrictibant 20 mg BID 1.8 +/- 2.25
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1 (Secondary), Mean, proportion of days: Placebo 0.163 +/- 0.1140; Deucrictibant 10 mg BID 0.044 +/- 0.0892; Deucrictibant 20 mg BID 0.021 +/- 0.0261
Time to First Investigator-confirmed HAE Attack in the Treatment Period in Part 1 (Secondary), Median, days: Placebo 9.0 (5.00 to 26.00); Deucrictibant 10 mg BID NA (19.00 to NA); Deucrictibant 20 mg BID 86.0 (13.00 to NA)
Number of Investigator-confirmed HAE Attacks Resulting in a Visit to the Emergency Department or an Admission to Hospital During the Treatment Period in Part 1 (Secondary), Least squares mean, attacks per month: Placebo 0 +/- 0; Deucrictibant 10 mg BID 0 +/- 0; Deucrictibant 20 mg BID 0 +/- 0
Number of Investigator-confirmed HAE Attacks During the Treatment Period in Part 2 (Secondary), Mean, attacks per month: Deucrictibant 20 mg BID 0.12 +/- 0.224
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 2 (Secondary), Least squares mean, attacks per month: Deucrictibant 20 mg BID 0.06 +/- 0.024
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 2 (Secondary), Least squares mean, attacks per month: Deucrictibant 20 mg BID 0.06 +/- 0.021
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2 (Secondary), Mean, days: Deucrictibant 20 mg BID 5.8 +/- 12.05
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2 (Secondary), Mean, proportion of days: Deucrictibant 20 mg BID 0.009 +/- 0.0173

Adverse events

Time frame: Double-blind treatment period: Day 0 to 84 Open-label treatment period:Day 85 to Day 938

Arm	Deaths	Serious adverse events	Other adverse events
Part 1: Placebo	0/11 (0.0%)	0/11 (0.0%)	7/11 (63.6%)
Part 1: Deucrictibant 10 mg BID	0/11 (0.0%)	0/11 (0.0%)	6/11 (54.5%)
Part 1: Deucrictibant 20 mg BID	0/12 (0.0%)	0/12 (0.0%)	7/12 (58.3%)
Part 2: Deucrictibant 20 mg BID	0/30 (0.0%)	2/30 (6.7%)	24/30 (80.0%)

Serious adverse events by term

Term	Organ system	Part 1: Placebo	Part 1: Deucrictibant 10 mg BID	Part 1: Deucrictibant 20 mg BID	Part 2: Deucrictibant 20 mg BID
Tendon injury	Injury, poisoning and procedural complications	0/11	0/11	0/12	1/30
Arthritis	Musculoskeletal and connective tissue disorders	0/11	0/11	0/12	1/30
Osteoarthritis	Musculoskeletal and connective tissue disorders	0/11	0/11	0/12	1/30

Other adverse events by term

Term	Organ system	Part 1: Placebo	Part 1: Deucrictibant 10 mg BID	Part 1: Deucrictibant 20 mg BID	Part 2: Deucrictibant 20 mg BID
Nasopharyngitis	Infections and infestations	1/11	2/11	0/12	12/30
Urinary tract infection	Infections and infestations	0/11	1/11	1/12	1/30
Gastrointestinal infection	Infections and infestations	1/11	0/11	1/12	2/30
Viral pharyngitis	Infections and infestations	0/11	1/11	0/12	0/30
Diarrhoea	Gastrointestinal disorders	0/11	1/11	1/12	2/30
Abdominal pain	Gastrointestinal disorders	1/11	1/11	0/12	4/30
Nausea	Gastrointestinal disorders	1/11	1/11	0/12	4/30
Toothache	Gastrointestinal disorders	0/11	0/11	1/12	1/30
Abdominal pain upper	Gastrointestinal disorders	2/11	0/11	0/12	1/30
Constipation	Gastrointestinal disorders	1/11	0/11	0/12	0/30
Dyspepsia	Gastrointestinal disorders	1/11	0/11	0/12	0/30
Vomiting	Gastrointestinal disorders	1/11	0/11	0/12	3/30
Gamma-glutamyltransferase increased	Investigations	0/11	1/11	1/12	1/30
Blood alkaline phosphatase increased	Investigations	0/11	1/11	0/12	0/30
Blood glucose increased	Investigations	0/11	1/11	0/12	0/30
Protein urine present	Investigations	0/11	0/11	1/12	0/30
Dysmenorrhoea	Reproductive system and breast disorders	0/11	0/11	1/12	1/30
Genital haemorrhage	Reproductive system and breast disorders	0/11	0/11	1/12	0/30
Heavy menstrual bleeding	Reproductive system and breast disorders	0/11	1/11	0/12	0/30
Vaginal discharge	Reproductive system and breast disorders	0/11	1/11	0/12	0/30
Menstruation irregular	Reproductive system and breast disorders	1/11	0/11	0/12	0/30
Chest pain	General disorders	0/11	0/11	1/12	1/30
Feeling cold	General disorders	0/11	0/11	1/12	1/30
Arthropod bite	Injury, poisoning and procedural complications	0/11	0/11	1/12	0/30
Ligament injury	Injury, poisoning and procedural complications	0/11	1/11	0/12	0/30
Ligament sprain	Injury, poisoning and procedural complications	1/11	0/11	0/12	0/30
Limb injury	Injury, poisoning and procedural complications	1/11	0/11	0/12	1/30
Muscle twitching	Musculoskeletal and connective tissue disorders	0/11	1/11	0/12	0/30
Back pain	Musculoskeletal and connective tissue disorders	1/11	0/11	0/12	0/30
Dizziness postural	Nervous system disorders	0/11	1/11	0/12	0/30
Headache	Nervous system disorders	1/11	0/11	0/12	2/30
Cough	Respiratory, thoracic and mediastinal disorders	0/11	0/11	1/12	1/30
Hot flush	Vascular disorders	0/11	1/11	0/12	0/30
Upper respiratory tract infection	Infections and infestations	0/11	0/11	0/12	5/30
Lower respiratory tract infection	Infections and infestations	0/11	0/11	0/12	2/30
Abdominal distension	Gastrointestinal disorders	0/11	0/11	0/12	2/30
COVID-19	Infections and infestations	0/11	0/11	0/12	1/30
Furuncle	Infections and infestations	0/11	0/11	0/12	1/30
Gastroenteritis	Infections and infestations	0/11	0/11	0/12	1/30
Gastroenteritis viral	Infections and infestations	0/11	0/11	0/12	1/30
Gingivitis	Infections and infestations	0/11	0/11	0/12	1/30
Herpes zoster	Infections and infestations	0/11	0/11	0/12	1/30
Lyme disease	Infections and infestations	0/11	0/11	0/12	1/30
Norovirus infection	Infections and infestations	0/11	0/11	0/12	1/30
Otitis media	Infections and infestations	0/11	0/11	0/12	1/30
Pneumonia	Infections and infestations	0/11	0/11	0/12	1/30
Respiratory tract infection	Infections and infestations	0/11	0/11	0/12	1/30
Sinusitis	Infections and infestations	0/11	0/11	0/12	1/30
Tonsillitis	Infections and infestations	0/11	0/11	0/12	1/30
Viral upper respiratory tract infection	Infections and infestations	0/11	0/11	0/12	1/30
Vulvovaginal candidiasis	Infections and infestations	0/11	0/11	0/12	1/30
Abdominal pain lower	Gastrointestinal disorders	0/11	0/11	0/12	1/30
Dental caries	Gastrointestinal disorders	0/11	0/11	0/12	1/30
Gastrooesophageal reflux disease	Gastrointestinal disorders	0/11	0/11	0/12	1/30
Tooth discolouration	Gastrointestinal disorders	0/11	0/11	0/12	1/30
Carpal tunnel syndrome	Nervous system disorders	0/11	0/11	0/12	1/30
Intercostal neuralgia	Nervous system disorders	0/11	0/11	0/12	1/30
Migraine	Nervous system disorders	0/11	0/11	0/12	1/30
Morton's neuralgia	Nervous system disorders	0/11	0/11	0/12	1/30
Myelopathy	Nervous system disorders	0/11	0/11	0/12	1/30

29 more terms not shown.

+Locations (19)

Facility	City	Country
Study site	Birmingham, Alabama	United States
Study site	Paradise Valley, Arizona	United States
Study site	St Louis, Missouri	United States
Study Site	Vienna	Austria
Study site	Sofia	Bulgaria
Study site	Ottawa, Ontario	Canada
Study site	Montreal, Quebec	Canada
Study site	Berlin	Germany
Study site	Frankfurt	Germany
Study site	Dublin	Ireland
Study site	Padua, PD	Italy
Study site	Milan	Italy
Study site	Palermo	Italy
Study site	Krakow	Poland
Study site	Brighton, England	United Kingdom
Study site	Bristol, England	United Kingdom
Study site	Cambridge, England	United Kingdom
Study site	London, England	United Kingdom
Study site	Southampton, England	United Kingdom

+Publications

Results publication: Aygoren-Pursun E, Stobiecki M, Valerieva A, Cancian M, Gompels M, Grigoriadou S, Kiani-Alikhan S, Kinaciyan T, Yang WH, Anderson J, Arcoleo F, Chapdelaine H, Conlon N, Eren E, Guarino MD, Gurugama P, Magerl M, Manning ME, Tarzi MD, Wedner HJ, Zanichelli A, Crabbe R, Mulders S, Levy J, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA. Oral deucrictibant for prophylaxis of hereditary angioedema attacks (CHAPTER-1): primary analysis of a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2026 Apr;13(4):e215-e226. doi: 10.1016/S2352-3026(26)00004-9. Epub 2026 Mar 19. PMID 41865746

+Study documents

Study Protocol (PDF, 2023-05-03)
Statistical Analysis Plan: Part 1 Data SAP (PDF, 2023-10-30)
Statistical Analysis Plan: Final Analysis SAP (PDF, 2023-10-30)

+Investigators

Marc Riedl, MD, Principal investigator, UC San Diego, La Jolla, California, United States
Emel Aygören-Pürsün, MD, Principal investigator, University Hospital Frankfurt - Goethe University, Frankfurt, Germany