A Dose Range-Finding Study to Assess the Efficacy and Safety of Multiple Dose Levels of AZD8630 in Adults With Uncontrolled Asthma at Risk of Exacerbations (Levante)

AstraZeneca

Status and phase: Enrolling; Phase 2

Conditions: Asthma

Treatments: Device: Inhaler; Drug: AZD8630; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06529419

D6830C00003

Details and patient eligibility

About

A dose range-finding study to assess the efficacy and safety of multiple dose levels of AZD8630 administered via a dry powder inhaler in adults with uncontrolled asthma at risk of exacerbations, receiving medium -to -high dose inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA).

Full description

This is a Phase II, randomised, placebo-controlled, double-blind, dose range-finding, multi-centre study to assess the efficacy and safety of inhaled AZD8630 administered at 3 doses via an inhaler in adult patients with uncontrolled asthma, at risk of an exacerbation. The study duration up to 57 weeks for participants in the optional safety extension study and up to 17 weeks for those not included. The maximal treatment period is up to 52 weeks.

This study will be conducted in approximately 220 centres in 20-25 countries. Approximately 516 patients will be randomised globally

Enrollment: 516 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Principal inclusion criteria (abbreviated):

1. Patient must be 18 to 80 years of age inclusive

2. Documented physician diagnosis of asthma for at least 12 months, with objective evidence of asthma (spirometric, bronchial challenge, exercise challenge or therapeutic response) within the last 5 years

3. Uncontrolled asthma (i.e. ACQ-6 ≥ 1.5)

4. Pre-BD FEV1 ≥ 40%

5. A history of asthma exacerbations within the last 12 months

6. & 9. Compliant with asthma background mediation, daily ePROs and daily home spirometry.

7. BMI within the range 18-37 kg/m2 (inclusive)

8. Female patients of child bearing potential must not be pregnant and agree to use highly effective contraception.

9. Male patients and their female partners of childbearing potential must agree to use highly effective contraception.

10. Capable of giving signed informed consent.

Principal exclusion criteria (abbreviated):

1. History of life-threatening asthma

2. Recently completed treatment for respiratory infection and/or asthma exacerbation

3. Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease.

4. Any disorder that is not stable in the opinion of the Investigator and could:

   1. Affect the safety of the patient throughout the study
   2. Influence the findings of the study or their interpretation
   3. 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.

6. Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C

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.

10. Patients with recent myocardial infarction, unstable angina pectoris, stroke, percutaneous coronary intervention or coronary artery bypass grafting.

11. A helminth parasitic infection diagnosed 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 ago.

13. Known history of drug or alcohol abuse within 12 months, that in the Investigator's opinion would preclude participation in the study.

14. Current diagnosis of cancer or unresectable cancer that has not been in complete remission for at least 5 years.

15. Any other clinically relevant abnormal findings 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.

16. Treatment with marketed or investigational biologics within 4 months or a minimum of 5 half-lives.

17. Treatment with Systemic steroids within 4 weeks.

18. Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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516 participants in 4 patient groups, including a placebo group

AZD8630 dose A

Experimental group

Description:

Inhaled AZD8630 administered at a dose A

Treatment:

Drug: AZD8630

Device: Inhaler

AZD8630 dose B

Experimental group

Description:

Inhaled AZD8630 administered at a dose B

Treatment:

Drug: AZD8630

Device: Inhaler

AZD8630 dose C

Experimental group

Description:

Inhaled AZD8630 administered at a dose C

Treatment:

Drug: AZD8630

Device: Inhaler

Placebo

Placebo Comparator group

Description:

Inhaled placebo

Treatment:

Drug: Placebo

Device: Inhaler