STOP-HAE: A Phase 3 Study of ADX-324 in HAE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Adarx Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

16 Jan 2026 → ongoing

Decision date (initial)

2025-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2025-521352-38-00

WHO UTN

U1111-1317-9190

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

To evaluate the efficacy of ADX 324 in preventing HAE attacks.

Secondary objectives 1

1. To evaluate the effects of ADX 324 on the quality and pattern of HAE attacks.

Conditions and MedDRA coding

Hereditary Angioedema

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Age ≥18 years.
2. 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.
3. 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.
4. 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.
5. 5. Subjects must be deemed medically appropriate for on-demand treatment as the sole medicinal management.

Exclusion criteria 6

1. 1. Concurrent diagnosis of another form of recurrent angioedema (acquired angioedema, HAE with normal C1-INH, idiopathic angioedema, and recurrent angioedema associated with urticaria).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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 and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 9

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Adarx Pharmaceuticals Inc.

Sponsor organisation

Adarx Pharmaceuticals Inc.

Address

5871 Oberlin Drive Suite 200

City

San Diego

Postcode

92121-3732

Country

United States

Scientific contact point

Organisation

Adarx Pharmaceuticals Inc.

Contact name

VP, Clinical Development

Public contact point

Organisation

Adarx Pharmaceuticals Inc.

Contact name

VP, Clinical Development

Third parties 7

Locations

11 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 677 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications