Efficacy and Safety Evaluation of Inhaled AZD8630 in Adults with Uncontrolled Asthma at Risk of Exacerbations: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-514228-18-00
- Protocol
- D6830C00003
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **AZD8630** compared to placebo on the time to the first CompEx Asthma event in patients with uncontrolled asthma who are at risk of exacerbations. This is clinically relevant as it aims to determine the potential of AZD8630 to delay or prevent asthma exacerbations, which are significant events that can lead to increased morbidity and healthcare utilization in this patient population.
Secondary objectives include:
- Evaluating the effect of AZD8630 compared to placebo on lung function.
- Assessing the impact of AZD8630 on asthma symptoms, asthma control, and quality of life.
- Investigating the effect of AZD8630 on asthma-related biomarkers.
- Evaluating the pharmacokinetics (PK) of AZD8630 and anti-drug antibodies (ADA).
Participants
The clinical trial involves a total of **405 participants** diagnosed with **asthma** who remain uncontrolled despite medium to high dose inhaled corticosteroids (ICS) plus long-acting beta-agonists (LABA) and are at risk of exacerbations. The study population includes both male and female subjects, aged between 18 to 80 years. Participants were selected based on specific criteria, including a documented physician diagnosis of asthma for at least 12 months and evidence of uncontrolled asthma, as demonstrated by an Asthma Control Questionnaire (ACQ-6) score of 1.5 or higher. The trial population is characterized by a requirement for stable treatment with medium- or high-dose ICS in combination with LABA, with the dose of ICS stable for at least 30 days prior to the initial visit. Lifestyle considerations such as compliance with asthma medication and daily assessments are emphasized, with a minimum of 80% compliance required during the run-in period. The trial includes a vulnerable population, and both genders are represented. Participants must be capable of providing informed consent and meet specific health criteria, including a body mass index (BMI) within the range of 18-37 kg/m². The study does not provide additional information on specific lifestyle habits such as diet or physical activity.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy and safety of multiple dose levels of inhaled AZD8630 in adults with **uncontrolled asthma** at risk of exacerbations. The trial will span a duration of 12 weeks, with participants receiving the study drug or placebo once daily. The primary objective is to assess the effect of AZD8630 compared to placebo on the time to the first CompEx Asthma event. Secondary endpoints include evaluating changes in lung function, asthma symptoms, asthma control, quality of life, and asthma-related biomarkers.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age, lung function, and asthma history. Following successful screening, participants will be randomized and commence the treatment phase. Throughout the trial, follow-up visits will be conducted to monitor safety, adherence, and efficacy parameters. The end-of-study visit will conclude the trial, where final assessments will be made to evaluate the overall impact of the treatment.
The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with study procedures, adverse events, or withdrawal of consent. Participants must maintain at least 80% compliance with daily assessments and asthma background medication during the run-in period to remain in the study. The trial aims to provide valuable insights into the potential benefits of AZD8630 for individuals with uncontrolled asthma, contributing to the development of more effective treatment strategies.
Treatment
The clinical trial involves the administration of **AZD8630**, an experimental medication formulated as an **inhalation powder**. The active substance in AZD8630 is a **human IgG1 lambda Fab fragment against thymic stromal lymphopoietin**, which is a protein-based therapeutic agent. The medication is delivered via inhalation using the Saphira device, a capsule-based platform designed to administer dry powder contained in size 3 capsules. The Saphira device is intended for the maintenance treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). The trial protocol specifies that AZD8630 is to be administered once daily for a period of 12 weeks. The maximum treatment period for the study is 52 weeks, although the specific dosage in milligrams is not detailed in the provided data.
In addition to the experimental treatment, the study includes a **placebo** group. The placebo is referred to as "AZD8630 Placebo" and is used to maintain the double-blind nature of the trial. The placebo is administered in the same manner as the active treatment, ensuring that participants and investigators remain unaware of the treatment allocation. The placebo is designed to mimic the appearance and administration route of the active drug, although specific details about its composition are not provided.
Participant compliance with the dosing schedule is monitored throughout the study. The trial aims to assess the efficacy and safety of multiple dose levels of AZD8630 in adults with uncontrolled asthma who are at risk of exacerbations. The primary objective is to evaluate the effect of AZD8630 compared to placebo on the time to the first CompEx Asthma event. The study is conducted under the sponsorship of AstraZeneca AB, and the investigational product is not classified as an orphan drug. The trial is not designed for pediatric populations, and the Saphira device used in the study does not have a CE mark.
Efficacy
The efficacy of the investigational product AZD8630 in the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the time to the first CompEx Asthma event in patients with uncontrolled asthma at risk of exacerbations. This endpoint will provide a direct measure of the product's impact on asthma exacerbations.
Secondary endpoints will include evaluations of lung function, asthma symptoms, asthma control, quality of life, and asthma-related biomarkers. Lung function will be assessed by changes from baseline in pre-bronchodilator (Pre-BD) and post-bronchodilator (Post-BD) forced expiratory volume in one second (FEV1), pre-BD forced expiratory flow at 25-75% (FEF25-75), and forced vital capacity (FVC), both in clinical settings and at home. Home measurements will include peak expiratory flow (PEF) at specified weeks (1, 2, 4, 6, 8). Asthma symptoms and control will be evaluated using weekly mean asthma symptom diary scores, the Asthma Control Questionnaire (ACQ-6), the Asthma Quality of Life Questionnaire (AQLQ+12), the St. George's Respiratory Questionnaire (SGRQ), and the Sino-Nasal Outcome Test (SNOT-22) for patients with chronic rhinosinusitis with nasal polyposis.
Biomarker assessments will focus on changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, and total immunoglobulin E (IgE) levels. Additionally, the pharmacokinetics of AZD8630 will be evaluated by measuring serum concentrations and anti-drug antibodies (ADA) incidence and titres. These assessments will be conducted at various time points throughout the 12-week treatment period to comprehensively evaluate the efficacy of AZD8630 in the target patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient must be 18 to 80 years of age inclusive, at the time of signing the ICF
- BMI within the range 18-37 kg/m2 (inclusive) at the time of signing the informed consent at Visit 1 and at Visit 2.
- Female patients: (a) All FOCBP must have a negative serum pregnancy test result at the Screening Visit (Visit 1) and a negative urine pregnancy test on the day of randomisation (prior to randomisation; Visit 2) and must not be lactating. (b) Females of non-childbearing potential who are < 55 years old must fulfil one of the following criteria at the Screening Visit: (i) Post-menopausal, defined as amenorrhoea for ≥ 12 months following cessation of all exogenous hormonal treatments and FSH levels in the post-menopausal range (historical data for FSH will be accepted). (ii) Permanent sterilisation includes hysterectomy, bilateral oophorectomy, and bilateral salpingectomy at least 6 weeks before screening and is confirmed by the medical records or follow-up hormone level assessment. Bilateral tubal ligation is not acceptable. (c) For females aged ≥ 55 years, post-menopausal is defined as having a history of ≥ 12 months amenorrhea, without an alternative cause, following cessation of all exogenous hormonal treatments. (d) FOCBP must be willing to use highly effective contraception measures with low user dependency from signing the ICF until 20 days after last dose of study intervention. FOCBP should be stable on their chosen method of birth control for at least 3 months before first dosing.
- Male patients: (a) Male patients and their FOCBP partner must be willing to use a highly effective contraception measure and should refrain from donating sperm or fathering a child from the first day of dosing until at least 20 days after last dose of study intervention.
- Capable of giving signed informed consent.
- Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative.
- Documented physician diagnosis of asthma for at least 12 months, as evidenced by any of the following: (a) Post-BD reversibility of FEV1 ≥ 12% and ≥ 200 mL within 5 years prior to Visit 1, or (b) PEF average daily variability > 10% over a 2-week period within 5 years prior to Visit 1, or (c) Variability of FEV1 > 12% and 200 mL between any 2 clinical visits within 5 years prior to Visit 1, or (d) Positive bronchial challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 from pre-challenge of ≥ 20% with standard doses of methacholine or ≥ 15% with standardised hyperventilation, hypertonic saline, or mannitol challenge, or (e) Positive exercise challenge test within 5 years prior to Visit 1. A positive test is defined as a fall in FEV1 of > 10% and > 200 mL from pre-challenge, or (f) Significant increase in lung function after 4 weeks of anti-inflammatory treatment with ICS-containing treatment (GINA 2023) within 5 years prior to Visit 1, defined as an increase in FEV1 > 12% and 200 mL (or PEF by >20%)
- Treated with medium- or high-dose ICS (as per GINA 2023) in combination with LABA (GINA Step 4 or 5 therapy); the dose of ICS must be stable for at least 30 days prior to Visit 1. The ICS can be contained within an ICS-LABA fixed-dose combination product. Note: Treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 30 days prior to Visit 1 is allowed.
- Demonstration of uncontrolled asthma through ACQ-6 score ≥ 1.5 at both Visit 1 and Visit 2.
- Pre-BD FEV1 ≥ 40% at both Visit 1 and Visit 2.
- A pre-BD/pre-study intervention dose FEV1 at Visit 2 that has not increased by ≥ 400 ml from the pre-BD FEV1 recorded at Visit 1.
- Patient has documented evidence of any of the following: (a) A history of 1 severe exacerbation within the last 12 months and either: (i) FeNO ≥ 25 ppb at the screening and randomisation visits (Visits 1 and 2) (ii) Eosinophil count ≥ 150 cells/µL, recorded at any point in the 12 months up to and including the Screening Visit (local testing can be carried out to confirm eligibility if eosinophil count not available in medical records within the last 12 months). (b) A history of ≥ 2 severe exacerbations within 12 months of Visit 1. A severe exacerbation is defined as an episode of symptoms of asthma worsening that results in at least one of the following: OCS use for 3 consecutive days, inpatient (≥ 24 hours) hospitalisation for asthma or emergency room or equivalent visit for asthma that results in systemic CS use.
- At least 80% compliance with usual asthma background medication during the run-in period based on the daily asthma ePROs.
- Minimum 80% compliance with daily assessments. Compliance is defined as completing the daily ePROs and PEF measurements (morning and evening) at least 80% of the time during the 14-day period prior to the randomisation visit (minimum of 11 days) preceding Vi
- Any patient at GINA step 5 (i.e. on high dose ICS plus LABA) for which an injectable biologic therapy for asthma is indicated (according to local prescribing guidance) must meet the following to be included Be unable or unwilling to receive an injectable biologic, or for whom such treatment is considered contraindicated or inappropriate in the opinion of the investigator. Documentation must be provided in the source records
Exclusion Criteria
- Life-threatening asthma defined as a history of significant asthma episode(s) involving intubation, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s).
- Completed treatment for respiratory infection and/or asthma exacerbation with systemic corticosteroids and/or antibiotics for > 3 days in the 4 weeks prior to Visit 1.
- Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the patient throughout the study (b) Influence the findings of the study or their interpretation (c) Impede the patient’s ability to complete the entire duration of study
- Patients who, in the opinion of the Investigator, have evidence of active TB or are currently on treatment for active or latent TB. Investigation for active or latent TB, with interferon gamma release assay (IGRA) and/or chest X-ray, should only be considered if deemed clinically indicated by the Principal Investigator.
- Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C, as defined by: (a) Positive test for HBsAg (b) Positive test for anti-HBc: Patients who test positive for anti-HBc antibody but negative for HBsAg may be enrolled if their hepatitis B virus DNA test result is negative (c) Positive test for anti-hepatitis C antibody: Patients who test positive for antihepatitis C antibody may be enrolled if their hepatitis C viral RNA test result is negative in the absence of liver cirrhosis
- Patients with history of HIV infection or who test positive for HIV.
- Congenital long QT syndrome or prolonged QTcF > 470 ms or history of QT prolongation associated with other medications that required discontinuation of that medication.
- Current untreated or uncontrolled arrhythmia (eg, multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia). Note: Patients with clinically significant sinus nodal disease/bradycardia or type 2 second- or third-degree atrioventricular block can be included if treated with a pacemaker
- Patients with recent myocardial infarction, unstable angina pectoris, stroke, or percutaneous coronary intervention within 3 months of Visit 1 or coronary artery bypass grafting within 6 months of Visit 1.
- A helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated, or has not responded to SoC therapy.
- Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and other recreational drugs including marijuana).
- Known history of drug or alcohol abuse within the 12 months prior to Visit 1, that in the Investigator’s opinion would preclude participation in the study. The use of oral cannabis is permitted.
- Current diagnosis of cancer or unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin and cervical carcinoma-in-situ that have been treated and considered cured at the time of enrolment are not exclusionary.
- Any other clinically relevant abnormal findings on vital signs, physical examination, or clinical laboratory testing including haematology, coagulation, clinical chemistry, or ECG between Visit 1 and Visit 2, that in the opinion of the Investigator or medical monitor might compromise the safety of the patient in the study or interfere with evaluation of the study intervention. Abnormal findings include, but are not limited to: (a) ALT or AST > 2 × ULN (b) TBL > 1.5 × ULN (unless due to Gilbert’s disease) Treatment with any of the following therapeutic interventions within the specified time before Visit 1
- Treatment with marketed or investigational biologics for asthma or immunological disease within 4 months or a minimum of 5 half-lives, prior to Visit 1, whichever is longer.
- Systemic steroids within 4 weeks prior to Visit 1.
- Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 23 Jan 2025 | 5 |
 Czechia | Not Recruiting | 23 Jan 2025 | 20 |
 Denmark | Not Recruiting | 23 Jan 2025 | 20 |
 France | Not Recruiting | 23 Jan 2025 | 10 |
 Germany | Not Recruiting | 23 Jan 2025 | 15 |
 Italy | Not Recruiting | 23 Jan 2025 | 8 |
 The Netherlands | Not Recruiting | 23 Jan 2025 | — |
 Slovakia | Not Recruiting | 23 Jan 2025 | 12 |
 Spain | Not Recruiting | 23 Jan 2025 | 15 |
| Netherlands | — | — | 5 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AZD8630 | Test | INHALATION POWDER | INHALATION USE | 00 | 52 | PRD11427663 |
AZD8630 | Test | INHALATION POWDER | INHALATION USE | 00 | 52 | PRD11334986 |
AZD8630 Placebo | Placebo | N/A | — | — | — | N/A |
AZD8630 | Test | INHALATION POWDER | INHALATION USE | 00 | 52 | PRD11334985 |