STAR-0215 for Hereditary Angioedema

Not currently recruiting at 29 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests STAR-0215, a treatment for hereditary angioedema (HAE), which causes sudden and painful swelling attacks. The trial aims to gather information on the long-term safety of STAR-0215 and its effectiveness when administered every 3 or 6 months as a subcutaneous injection. Individuals diagnosed with HAE (Type 1 or Type 2) who have not participated in a previous STAR-0215 trial might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in HAE treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that STAR-0215 is being tested for safety and effectiveness in treating hereditary angioedema (HAE). Earlier studies found STAR-0215 to be safe. Participants experienced fewer and less severe HAE attacks, and fewer required extra medication. These results suggest that most patients tolerate the treatment well. While researchers gather more long-term information, current evidence supports its potential safety for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for hereditary angioedema?

Unlike the standard treatments for hereditary angioedema, which often involve frequent dosing schedules, STAR-0215 offers a potentially game-changing approach with its extended dosing intervals. Researchers are excited about STAR-0215 because it can be administered every 3 to 6 months, significantly reducing the burden of frequent treatments. Additionally, STAR-0215 is delivered via subcutaneous injection, which might be more convenient compared to some existing therapies. This treatment's innovative approach could lead to improved quality of life for patients with hereditary angioedema by simplifying their treatment regimen.

What evidence suggests that STAR-0215 could be an effective treatment for hereditary angioedema?

Research shows that STAR-0215, also known as navenibart, may reduce the frequency and severity of attacks in people with hereditary angioedema (HAE). Early studies found that 50% of patients experienced no attacks for six months. Patients also reported fewer severe attacks and less need for emergency medication. Navenibart blocks plasma kallikrein, a protein involved in causing HAE attacks. Initial research indicates that the body tolerates it well and that it has long-lasting effects. This promising evidence suggests it could be a useful option for managing HAE. Participants in this trial will receive STAR-0215 in different dosing regimens to evaluate its effectiveness and safety. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ir.astriatx.com ir.astriatx.com/news-releases/news-release-details/astria-therapeutics-announces-positive-initial-results-alpha

Astria Therapeutics Announces Positive Initial Results from ... Navenibart demonstrated overall attack-freedom of 50% over six months, which is the longest period of follow-up for all 16 patients to date.

2. jacionline.org jacionline.org/article/S0091-6749(24)01898-0/fulltext

Treatment with Navenibart (STAR-0215) Reduces Attack ... This interim analysis suggests that navenibart reduces the burden of HAE, assessed by reduction in HAE attack frequency, severity and use of rescue medication.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06842823

NCT06842823 | A Study of Navenibart in Participants With ... The goal of this clinical trial is to evaluate the efficacy and safety of navenibart compared to placebo in preventing HAE attacks in participants with HAE.

4. sciencedirect.com sciencedirect.com/science/article/pii/S108112062500153X

Safety and pharmacokinetics of long-acting plasma ... In this first-in-human study, up to 1200 mg of navenibart was well tolerated and demonstrated an extended half-life with durable plasma kallikrein inhibition.

5. astriatx.com astriatx.com/our-science/our-pipeline/star-0215/

Navenibart (STAR-0215) Navenibart is in clinical development for the treatment of hereditary angioedema. Based on positive results from the ALPHA-STAR Phase 1b/2 trial in people ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06007677

NCT06007677 | A Long-term Study of STAR-0215 in ... 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 ...