A trial to learn how safe AZD8630 is and how well it works in adults with uncontrolled asthma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

16 Jan 2025 → ongoing

Decision date (initial)

2024-12-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-514228-18-00

ClinicalTrials.gov

NCT06529419

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Dose response, Efficacy, Therapy, Safety, Pharmacokinetic

To evaluate the effect of AZD8630 as compared to placebo on time to first CompEx Asthma event in patients with uncontrolled asthma at risk of exacerbations.

Secondary objectives 4

1. To evaluate the effect of AZD8630 as compared to placebo on lung function
2. To evaluate the effect of AZD8630 as compared to placebo on asthma symptoms, asthma control and quality of life.
3. To evaluate the effect of AZD8630 as compared with placebo on asthma-related biomarkers.
4. To evaluate the PK of AZD8630 and ADA.

Conditions and MedDRA coding

Asthma in adults who remain uncontrolled despite medium to high dose ICS plus LABA, and who are at risk of exacerbations.

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

AstraZeneca AB

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patient must be 18 to 80 years of age inclusive, at the time of signing the ICF
2. BMI within the range 18-37 kg/m2 (inclusive) at the time of signing the informed consent at Visit 1 and at Visit 2.
3. 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.
4. 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.
5. Capable of giving signed informed consent.
6. 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.
7. 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%)
8. 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.
9. Demonstration of uncontrolled asthma through ACQ-6 score ≥ 1.5 at both Visit 1 and Visit 2.
10. Pre-BD FEV1 ≥ 40% at both Visit 1 and Visit 2.
11. 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.
12. 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.
13. At least 80% compliance with usual asthma background medication during the run-in period based on the daily asthma ePROs.
14. 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
15. 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 18

1. Life-threatening asthma defined as a history of significant asthma episode(s) involving intubation, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s).
2. 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.
3. Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease.
4. 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
5. 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.
6. 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
7. Patients with history of HIV infection or who test positive for HIV.
8. Congenital long QT syndrome or prolonged QTcF > 470 ms or history of QT prolongation associated with other medications that required discontinuation of that medication.
9. 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
10. 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.
11. A helminth parasitic infection diagnosed within 24 weeks of Visit 1 that has not been treated, or has not responded to SoC therapy.
12. 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).
13. 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.
14. 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.
15. 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
16. 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.
17. Systemic steroids within 4 weeks prior to Visit 1.
18. Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first CompEx Asthma event

Secondary endpoints 4

1. To evaluate the effect of AZD8630 as compared to placebo on lung function: Change from baseline to: Measured in the clinic: 1 Pre-BD FEV1 2 Post-BD FEV1 3 Pre-BD FEF25-75 4 Pre-BD FVC 5 Post-BD FVC Measured in the home 6. PEF: Weeks 1, 2, 4, 6, 8, 7. maximum pre-BD
2. To evaluate the effect of AZD8630 as compared to placebo on asthma symptoms, asthma control and quality of life Change from baseline to: 1 Weekly mean asthma symptom diary score: 2 ACQ-6 3 AQLQ+12 4 SGRQ 5 SNOT-22 (for patients with chronic rhinosinusitis with nasal polyposis)
3. To evaluate the effect of AZD8630 as compared with placebo on asthma-related biomarkers Change from baseline to: 1 FeNO 2 Blood eosinophils 3 Total IgE
4. To evaluate the pharmacokinetics (PK) of AZD8630 and ADA AZD8630 serum concentrations and ADA (incidence and titres).

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

9 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 111 files

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

Application history

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