Clinical trial • Phase III • Immunology|Rare Disease
ADX-324 for Hereditary angioedema
Phase III trial of ADX-324 for Hereditary angioedema.
Overview
- Trial Therapeutic Area
- Immunology|Rare Disease
- Trial Disease
- Hereditary angioedema
- Trial Stage
- Phase III
- Drug Modality
- Other RNA|Other
Key dates
- Initial CTIS Submission Date
- 27-06-2025
- First CTIS Authorization Date
- 22-10-2025
Trial design
Randomised, placebo: sterile normal saline (0.9% sodium chloride solution) administered to group 3 (placebo). group assignments: adx-324 treatment group 1 (dose every 6 months), adx-324 treatment group 2 (dose every 3 months). participants in group 3 are randomly assigned to receive dose 1 or dose 2 of normal saline (placebo) according to the study schedule.-controlled Phase III trial in Italy, Poland, Belgium and others.
- Randomised
- Yes
- Comparator
- Placebo: Sterile normal saline (0.9% sodium chloride solution) administered to Group 3 (placebo). Group assignments: ADX-324 Treatment Group 1 (dose every 6 months), ADX-324 Treatment Group 2 (dose every 3 months). Participants in Group 3 are randomly assigned to receive Dose 1 or Dose 2 of normal saline (placebo) according to the study schedule.
- Target Sample Size
- 90
- Trial Duration For Participant
- 175
Stratification factors
- Baseline HAE attack rate (1 to <2 attacks per 4 weeks)
- Baseline HAE attack rate (2 to <3 attacks per 4 weeks)
- Baseline HAE attack rate (≥3 per 4 weeks)
Eligibility
Recruits 90 adults.
Inclusion criteria
- {"criterion_text":"- 1. Age ≥18 years.\n- 2. Have a documented diagnosis of HAE-1or HAE-2 based upon ALL of the following (a, b, AND c): a) Documented clinical history consistent with HAE b) Diagnostic testing (historical documentation or during Screening, with option of one repeat test) that confirms 2 of the following: 1.C1-INH antigen level <50% the lower limit of normal (LLN). 2.C1-INH functional level <50% LLN. 3.C1-INH function ≥50% but ≤60% and a pathogenic mutation in the SERPING1 gene. 4.complement factor C4 level below the LLN. c) Have at least one of the following: 1.Age ≤30 years at reported HAE onset. 2.A family history consistent with HAE-1/HAE-2. 3.Complement component 1q within the normal range.\n- 3. Must experience ≥1 Investigator-confirmed HAE attacks during the first 4-weeks of Screening or ≥2 Investigator-confirmed HAE attacks in 8 weeks of Screening.\n- 4. Have access to, and the ability to use, acute HAE therapy to treat HAE attacks (e.g., plasma-derived or recombinant C1-INH concentrate or a BK2-receptor antagonist) that has been previously shown to be effective for the subject.\n- 5. Subjects must be deemed medically appropriate for on-demand treatment as the sole medicinal management."}
Exclusion criteria
- {"criterion_text":"- 1. Concurrent diagnosis of another form of recurrent angioedema (acquired angioedema, HAE with normal C1-INH, idiopathic angioedema, and recurrent angioedema associated with urticaria).\n- 2. History of alcohol or drug abuse within the previous year prior to Screening, or current evidence of substance dependence or abuse and/or self-reported alcoholic intake averaging >3 drinks/day.\n- 3. Any clinically significant medical history including, but not limited to, uncontrolled HTN, uncontrolled DM, or current cardiovascular disease, including recent acute coronary syndrome (within the past 6 months), CHF (NYHA Class III or IV), significant arrhythmias, substance abuse, significant renal disease (CKD Stage 3 eGFR<60 ml/min/1.73 m²) h/o Nephrotic Syndrome), significant hepatic disease, h/o coagulopathies or bleeding diathesis, malignancy within 5 years, active infection (viral, bacterial, fungal, or parasitic) requiring systemic antimicrobial therapy, known HIV infection or positive serology test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) during screening, Major surgery or significant traumatic injury within 30 days prior to signing the ICF.\n- 4. Exposure to any of the following LTP for HAE: a. Chronic prophylaxis with C1-INH (CINRYZE, HAEGARDA, RUCONEST) within 2 weeks prior to Screening. b.Chronic prophylaxis with berotralstat (ORLADEYO) within 3 weeks prior to Screening. c. Chronic prophylaxis with lanadelumab (TAKHZYRO) within 8 weeks prior to the Screening. d. Androgen use within 12 weeks prior to Screening.\n- 5. Exposure to any of the following medications: a. ACE inhibitors within 4 weeks prior to Screening. b. New use of or increase in dose of estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within3 months prior to Screening. Participants on a stable dose of estrogen-containing medications for ≥3 months prior to Screening are eligible.\n- 6. Received prior treatment with any RNA/DNA-based therapy for HAE (including ADX-324) or is intolerant of any prior RNA/DNA-based therapy for any condition, excluding vaccines."}
Endpoints
Primary endpoints
- {"endpoint_text":"- The time-normalized number of Investigator-confirmed HAE attacks (per month) from Study Day 22 to the Week 25 Visit for ADX 324 vs placebo.","definition_or_measurement_approach":"Time-normalized number of Investigator-confirmed HAE attacks per month measured from Study Day 22 to the Week 25 visit; comparison ADX-324 versus placebo."}
Secondary endpoints
- {"endpoint_text":"- The time-normalized number of Investigator-confirmed HAE attacks (per month) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"Same measure as primary: time-normalized investigator-confirmed HAE attacks per month from Study Day 22 to Week 25; ADX-324 vs placebo."}
- {"endpoint_text":"- The time-normalized number of Investigator-confirmed HAE attacks requiring acute HAE therapy (per month) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"Time-normalized monthly rate of investigator-confirmed HAE attacks that required acute HAE therapy, measured from Study Day 22 to Week 25; ADX-324 vs placebo."}
- {"endpoint_text":"- The time-normalized number of Investigator-confirmed HAE attacks requiring acute HAE therapy (per month) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"As above (measure repeated in listing): monthly rate of investigator-confirmed HAE attacks requiring acute therapy from Study Day 22 to Week 25; ADX-324 vs placebo."}
- {"endpoint_text":"- The time-normalized number of moderate or severe Investigator confirmed HAE attacks (per month) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"Time-normalized monthly rate of investigator-confirmed moderate or severe HAE attacks between Study Day 22 and Week 25; ADX-324 vs placebo."}
- {"endpoint_text":"- The time-normalized number of moderate or severe Investigator confirmed HAE attacks (per month) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"As above (duplicate listing): monthly rate of moderate or severe investigator-confirmed HAE attacks from Study Day 22 to Week 25."}
- {"endpoint_text":"- The proportion of participants who have not experienced an Investigator-confirmed HAE attack (HAE attack-free) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"Proportion of participants without any investigator-confirmed HAE attack between Study Day 22 and Week 25, ADX-324 versus placebo."}
- {"endpoint_text":"- The proportion of participants who have not experienced an Investigator-confirmed HAE attack (HAE attack-free) from Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"As above (duplicate listing): proportion attack-free between Study Day 22 and Week 25."}
- {"endpoint_text":"- The proportion of participants with a clinical response defined as a reduction from baseline (ie, Screening rate) in Investigator-confirmed HAE attack rate between Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"Proportion of participants achieving a clinical response defined as reduction from baseline (screening rate) in investigator-confirmed HAE attack rate between Study Day 22 and Week 25; ADX-324 vs placebo."}
- {"endpoint_text":"- The proportion of participants with a clinical response defined as a reduction from baseline (ie, Screening rate) in Investigator-confirmed HAE attack rate between Study Day 22 to the Week 25 Visit for ADX-324 vs placebo.","definition_or_measurement_approach":"As above (duplicate): proportion with reduction from baseline in investigator-confirmed HAE attack rate between Study Day 22 and Week 25."}
Recruitment
- Registry Or Advocacy Recruitment
- True, PAG (patient advocacy groups)
- Digital Remote Recruitment
- True, includes Google Ads, social media ads, website banners, PatientGO/StudyKIK patient app eDiary and Patient Concierge app, patient recruitment videos and online screener forms (country-specific digital materials).
- Planned Sample Size
- 90
- Recruitment Window Months
- 14
- Consent Approach
- Informed consent is obtained from adult participants (Age ≥18) using L1_SIS and ICF Main and related subject information materials. Optional/supplemental ICFs are provided for optional testing, mobile nursing, pregnant partner/participant, and use of patient concierge/app services. Consent and subject information documents are provided in multiple languages and country-specific versions (examples present in documents: EN, IT, PL, BE (NL/FR/EN), DE, HU, HR, FR, BG, CZ, ES).
Methods
- Online advertising: Google Ads and website banner ads (country-specific materials present: IT, PL, BE, HR, HU, FR, AT, DE, BG, CZ, ES).
- Social media advertising: social media ads, LinkedIn dark ads, social media content plans (patient-targeted).
- Healthcare professional outreach: Dr-to-dr letters, HCP ad visuals, HCP study flyers, HCP sign-up forms (to engage referring clinicians).
- Patient-targeted materials: patient brochures, patient flyers, posters with tear-off flyers, patient recruitment video/storyboard, patient study drug flyers.
- Patient advocacy engagement: PAG (patient advocacy group) letters and PAG-to-patient materials to reach advocacy networks.
- Digital patient app/remote engagement: PatientGO / StudyKIK patient app materials, Patient Concierge registration and PatientGO EULA; patient eDiary text files and app-based consent/information.
- Traditional site-based recruitment: site study visit guides, site reference cards, local posters/flyers and clinic-based referral (country/site-specific).
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 36
Italy
- Earliest CTIS Part Ii Submission Date
- 07-10-2025
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 210
- Number Of Sites
- 2
- Number Of Participants
- 6
Sites
- Site Name
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
- Department Name
- UOC Patologia Clinica-Centro Angioedema
- Contact Person Name
- Francesco Arcoleo
- Contact Person Email
- farcoleo@villasofia.it
- Site Name
- Azienda Ospedaliera di Padova
- Department Name
- UOSD Allergologia
- Contact Person Name
- Mauro Cancian
- Contact Person Email
- mcancian@unipd.it
Poland
- Earliest CTIS Part Ii Submission Date
- 22-09-2025
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 225
- Number Of Sites
- 4
- Number Of Participants
- 5
Sites
- Site Name
- Umed Clinical Trials Sp. z o.o.
- Contact Person Name
- Marcin Kurowski
- Contact Person Email
- badania.kliniczne@umed.lodz.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Klinika Alergologii i Chorob Wewnetrznych
- Contact Person Name
- Robert Pawlowicz
- Contact Person Email
- kwg@usk.wroc.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu (site 2)
- Department Name
- Klinika Alergologii i Chorob Wewnetrznych
- Contact Person Name
- Robert Pawlowicz
- Contact Person Email
- kwg@usk.wroc.pl
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
- Department Name
- Centrum Alergologii – Poradnia Alergologiczna
- Contact Person Name
- Marcin Stobiecki
- Contact Person Email
- centrumalergologii@su.krakow.pl
Belgium
- Earliest CTIS Part Ii Submission Date
- 20-09-2025
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 222
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Universitair Ziekenhuis Antwerpen
- Department Name
- Immunology – Allergology – Rheumatology
- Contact Person Name
- Didier Ebo
- Contact Person Email
- Didier.Ebo@uza.be
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Hematology, Haemostasis and Thrombosis Unit
- Contact Person Name
- Cedric Hermans
- Contact Person Email
- Cedric.hermans@saintluc.uclouvain.be
Croatia
- Earliest CTIS Part Ii Submission Date
- 19-09-2025
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 228
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- KBC Split
- Department Name
- Rheumatology and Clinical Immunology Department
- Contact Person Name
- Dijana Perkovic
- Contact Person Email
- dijana.perkovic@hotmail.com
- Site Name
- University Hospital Centre Zagreb
- Department Name
- Department of Internal Medicine
- Contact Person Name
- Marko Baresic
- Contact Person Email
- markobaresic@gmail.com
Hungary
- Earliest CTIS Part Ii Submission Date
- 22-08-2025
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 255
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Semmelweis University
- Department Name
- Internal Medicine and Haematology Clinic
- Contact Person Name
- Henriette Farkas
- Contact Person Email
- Farkas.henriette@med.semmelweis-univ.hu
Spain
- Earliest CTIS Part Ii Submission Date
- 22-09-2025
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 220
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Bellvitge University Hospital
- Department Name
- Allergology
- Contact Person Name
- Ramon Lleonart Bellfill
- Contact Person Email
- rlleonart@bellvitgehospital.cat
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Allergology
- Contact Person Name
- Alicia Prieto Garcia
- Contact Person Email
- alicia.prieto@salud.madrid.org
Bulgaria
- Earliest CTIS Part Ii Submission Date
- 09-10-2025
- Latest Decision Or Authorization Date
- 05-05-2026
- Processing Time Days
- 208
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Diagnostics And Consultation Center Convex Ltd.
- Department Name
- Not applicable
- Contact Person Name
- Anna Valerieva
- Contact Person Email
- anna.valerieva@gmail.com
Austria
- Earliest CTIS Part Ii Submission Date
- 09-10-2025
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 207
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Department of Dermatology
- Contact Person Name
- Tamar Kinaciyan
- Contact Person Email
- Tamar.kinaciyan@meduniwien.ac.at
France
- Earliest CTIS Part Ii Submission Date
- 20-09-2025
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 222
- Number Of Sites
- 4
- Number Of Participants
- 4
Sites
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Hôpital Saint Éloi - Service de Dermatologie
- Contact Person Name
- Aurélie DU-THANH
- Contact Person Email
- a-du_thanh@chu-montpellier.fr
- Site Name
- Centre Hospitalier Regional Universitaire De Tours
- Department Name
- Hôpital Bretonneau - Service Transversal d’Allergologie et Immunologie Clinique
- Contact Person Name
- Cyrille HOARAU
- Contact Person Email
- hoarauc@med.univ-tours.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Hôpital Saint Antoine - Service de Médecine Interne
- Contact Person Name
- Olivier FAIN
- Contact Person Email
- olivier.fain@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Nice
- Department Name
- Hôpital Archet 1 - Service de Médecine Interne
- Contact Person Name
- Pierre-Yves JEANDEL
- Contact Person Email
- jeandel.py@chu-nice.fr
Czechia
- Earliest CTIS Part Ii Submission Date
- 19-09-2025
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 227
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Fakultni Nemocnice V Motole
- Department Name
- Ustav imunologie 2.LF UK a FN Motol
- Contact Person Name
- Marta Sobotkova
- Contact Person Email
- marta.sobotkova@fnmotol.cz
- Site Name
- Fakultni Nemocnice Hradec Kralove
- Department Name
- Ustav klinicke imunologie and alergologie
- Contact Person Name
- Pavlina Kralickova
- Contact Person Email
- pavlina.kralickova@fnhk.cz
Germany
- Earliest CTIS Part Ii Submission Date
- 06-10-2025
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 210
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Universitäts-Hautklinik Tübingen Studienzentrum Immundermatologie
- Contact Person Name
- Sebastian Volc
- Contact Person Email
- sebastian.volc@med.uni-tuebingen.de
Sponsor
Primary sponsor
- Full Name
- Adarx Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Medrio Inc.
- Responsibilities
- sponsorDuties codes: 3, 7 (as listed)
- Name
- PPD Development LP
- Responsibilities
- Central lab for Safety & Exploratory assays; sponsorDuties codes: 15, 4
- Name
- Syneos Health Inc.
- Responsibilities
- Multiple sponsor duties (codes: 1, 10, 11, 12, 2, 5, 8)
- Name
- Cmic Inc.
- Responsibilities
- sponsorDuties code: 4
Third parties
- {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"sponsorDuties codes: 3, 7; contact kmonaghan@medrio.com","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"MyData-TRUST","duties_or_roles":"Data Protection Officer (role value provided)","organisation_type":"Industry"}
- {"country":"Australia","full_name":"Agilex Biolabs Pty Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Central lab for Safety & Exploratory assays; sponsorDuties codes: 15 (Central lab), 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Thermo Fisher Scientific Inc.","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: 1, 10, 11, 12, 2, 5, 8","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Cmic Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- ADX-324
- Active Substance
- ADX-324
- Modality
- Other RNA
- Routes Of Administration
- SUBCUTANEOUS INJECTION
- Route
- SUBCUTANEOUS INJECTION
- Authorisation Status
- prodAuthStatus:1 (as listed in productDictionaryInfo)
- Frequency
- Group 1: every 6 months; Group 2: every 3 months (per arm descriptions)
- Investigational Product Name
- Sterile normal saline (0.9% sodium chloride solution)
- Modality
- Other
- Frequency
- Placebo dosing assigned to Group 3; participants randomized to Dose 1 or Dose 2 of normal saline (per arm details)
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