STAR-0215 for Hereditary Angioedema

Recruiting at 22 trial locations

Overseen By Christopher Morabito, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Astria Therapeutics, Inc.

Must not be taking: ACE inhibitors, Estrogens, Androgens, others

Disqualifiers: Chronic angioedema, HAE Type III, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 5 years

56 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you should not have used angiotensin-converting enzyme inhibitors, estrogen-containing medications, or certain androgens shortly before the trial. Additionally, if you are on preventive therapies for HAE, there are specific timeframes you must follow before participating.

What data supports the effectiveness of the drug STAR-0215 (Navenibart) for hereditary angioedema?

While there is no direct data on STAR-0215 (Navenibart) for hereditary angioedema, similar treatments like donidalorsen have shown effectiveness in reducing attack frequency and improving quality of life in patients with hereditary angioedema. ^{1 2 3 4 5}

How does the drug STAR-0215 (Navenibart) differ from other treatments for hereditary angioedema?

STAR-0215 (Navenibart) is unique because it may offer a novel mechanism of action or administration route compared to existing treatments like stanozolol, which is an androgen, and ecallantide, a protein inhibitor. While stanozolol requires careful dose management due to side effects, and ecallantide is used for acute attacks, STAR-0215 could provide a different approach, potentially with fewer side effects or a more convenient dosing schedule. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this trial is to enable the collection of information about long-term safety and clinical activity of STAR-0215 in participants with hereditary angioedema (HAE). Participants will receive repeat doses of STAR-0215 for up to 5 years.

Eligibility Criteria

This trial is for people with hereditary angioedema who participated in a previous STAR-0215 study and met certain conditions. They shouldn't have used ACE inhibitors, estrogen medications, or androgens recently, nor should they have other chronic angioedema types or be on preventive HAE therapies without consulting the medical monitor.

Inclusion Criteria

Open to participants from STAR-0215-201 (NCT05695248) who have met specific conditions related to completion of the trial or entry into the Run-In period

Discontinued STAR-0215-201 (for reasons other than safety) after having completed at least 84 days of trial follow-up since their last dose of STAR-0215 (eligibility requires consultation with the Medical Monitor)

Exclusion Criteria

I have not taken ACE inhibitors or estrogen medications in the last 28 days.

I have used specific medications for preventing HAE attacks as per the given timelines.

I have been diagnosed with a chronic form of angioedema other than hereditary.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repeat doses of STAR-0215 for up to 5 years

5 years

Every 3 months for first 2 years, every 6 months for next 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• STAR-0215

Trial Overview The trial tests the long-term safety and effectiveness of repeated doses of STAR-0215 in individuals with hereditary angioedema. It's designed to last up to five years, gathering extensive data on how well this treatment works over time.

Participant Groups

Group I: Dose Regimen 3 (Arm D): STAR-0215 Experimental Treatment 1 Intervention

STAR-0215 will be administered as a subcutaneous injection.

Group II: Dose Regimen 2 (Arm B): STAR-0215 Experimental Treatment 1 Intervention

Participants will receive STAR-0215 every 6 months.

Group III: Dose Regimen 1 (Arm C): STAR-0215 Experimental Treatment 1 Intervention

STAR-0215 will be administered as a subcutaneous injection.

Group IV: Dose Regimen 1 (Arm A): STAR-0215 Experimental Treatment 1 Intervention

Participants will receive STAR-0215 every 3 months.

Who Is Running the Clinical Trial?

Astria Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

310+

Findings from Research

Patients with hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) tend to be older at disease onset and experience more abdominal and laryngeal attacks compared to those with HAE type I.

Icatibant is effective for treating angioedema attacks in both HAE-nC1 INH and HAE type I, but it takes longer to resolve attacks in HAE-nC1 INH patients, with no serious side effects reported, highlighting its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. Bouillet, L., Boccon-Gibod, I., Launay, D., et al.[2018]

Conestat alfa (Ruconest) is the first recombinant C1 esterase inhibitor specifically developed to treat acute attacks in patients with hereditary angioedema, a condition that causes severe swelling.

This treatment represents a significant advancement in managing hereditary angioedema, providing a targeted approach to alleviate symptoms during acute episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conestat alfa (ruconest): first recombinant c1 esterase inhibitor for the treatment of acute attacks in patients with hereditary angioedema. Cruz, MP.[2022]

In a 2-year interim analysis of a phase 2 open-label extension study involving 17 patients, donidalorsen demonstrated a remarkable 96% reduction in the frequency of hereditary angioedema (HAE) attacks compared to baseline, indicating strong efficacy.

The treatment was well tolerated with no serious adverse events reported, suggesting that donidalorsen is a safe option for managing HAE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema. Petersen, RS., Bordone, L., Riedl, MA., et al.[2023]

Cinryze (C1-esterase inhibitor) provided significant relief from hereditary angioedema attacks in children, with a median time to relief of 30 minutes compared to 2 hours for placebo, demonstrating its efficacy in acute management.

In prophylaxis, Cinryze reduced the frequency of attacks by about 50%, with the median monthly attack rate dropping from 3.0 to 0.39, indicating its effectiveness in preventing future episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. Lumry, W., Manning, ME., Hurewitz, DS., et al.[2013]

In a study of 28 patients with hereditary angioedema (HAE) with normal C1-INH, Berinert® was found to be effective in treating acute attacks, with 22 out of 38 assessed attacks showing improvement within 60 minutes of treatment.

No severe adverse effects were reported, indicating that Berinert® is a safe treatment option for patients with HAE, including those with F12 gene mutations or unknown origins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor: clinical characteristics and treatment response with plasma-derived human C1 inhibitor concentrate (Berinert®) in a French cohort. Bouillet, L., Boccon-Gibod, I., Gompel, A., et al.[2017]

Stanozolol is an effective treatment for hereditary angioedema, allowing patients to manage their symptoms with a gradual adjustment to the minimal effective dose, which can lead to reduced frequency of attacks.

While 18 out of 37 patients experienced side effects, primarily related to liver function and hormonal changes, these were manageable by adjusting the dosage, indicating that with careful monitoring, stanozolol can be safely used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema: a decade of management with stanozolol. Sheffer, AL., Fearon, DT., Austen, KF.[2019]

Ecallantide, a 30 mg subcutaneous treatment, significantly improved symptoms of acute hereditary angioedema (HAE) within 4 hours compared to placebo, as shown in two phase III trials (EDEMA3 and EDEMA4).

The treatment was generally well tolerated, with most adverse events being mild to moderate, and no serious side effects occurring in more than 10% of patients, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ecallantide: in acute hereditary angioedema. Garnock-Jones, KP.[2021]

Budesonide demonstrated a strong ability to inhibit the release of key inflammatory cytokines (IL-4, IL-6, IL-8, GM-CSF, and TNF-alpha) from human mast cells, showing greater potency than the systemic steroid dexamethasone and the H1 antagonist desloratadine.

The study found that the inhibitory effects of budesonide were time- and concentration-dependent, with IL-4 being the most affected cytokine, indicating its potential effectiveness in managing allergic and inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitory effects of budesonide, desloratadine and dexamethasone on cytokine release from human mast cell line (HMC-1). Zhao, Y., Leung, PC., Woo, KS., et al.[2022]

In a study of 32 patients with moderate-to-severe scalp seborrhoeic dermatitis, the combination calcipotriol plus betamethasone dipropionate (CBD) gel showed significant efficacy, with 59.4% of patients achieving complete clearance by week 10.

The treatment also led to marked improvements in itching and discomfort scores, indicating that CBD gel could be a valuable option for patients who do not respond well to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Combination Calcipotriol plus Betamethasone Dipropionate Gel in the Treatment of Moderate-to-Severe Scalp Seborrhoeic Dermatitis. Yap, FB.[2022]

Clobetasol propionate 0.05% emulsion foam is effective in treating moderate-to-severe atopic dermatitis and mild-to-moderate plaque-type psoriasis, with significantly higher treatment success rates compared to vehicle foam in two phase III studies involving 874 participants aged 12 years and older.

While the foam is generally safe, reversible suppression of the hypothalamic-pituitary-adrenal axis was observed in 27% of adults and 47% of younger children (ages 6-12), indicating a need for caution in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clobetasol propionate emulsion formulation foam 0.05%: review of phase II open-label and phase III randomized controlled trials in steroid-responsive dermatoses in adults and adolescents. Kimball, AB., Gold, MH., Zib, B., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Conestat alfa (ruconest): first recombinant c1 esterase inhibitor for the treatment of acute attacks in patients with hereditary angioedema. [2022]

3. Denmark pubmed.ncbi.nlm.nih.gov

A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. [2013]

5. France pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor: clinical characteristics and treatment response with plasma-derived human C1 inhibitor concentrate (Berinert®) in a French cohort. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Hereditary angioedema: a decade of management with stanozolol. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ecallantide: in acute hereditary angioedema. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibitory effects of budesonide, desloratadine and dexamethasone on cytokine release from human mast cell line (HMC-1). [2022]

9. Oman pubmed.ncbi.nlm.nih.gov

The Role of Combination Calcipotriol plus Betamethasone Dipropionate Gel in the Treatment of Moderate-to-Severe Scalp Seborrhoeic Dermatitis. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Clobetasol propionate emulsion formulation foam 0.05%: review of phase II open-label and phase III randomized controlled trials in steroid-responsive dermatoses in adults and adolescents. [2013]