Clinical trial NCT06529419: 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
Official title: A Phase 2b, Randomised, Double-Blind, Placebo-Controlled Dose Range-Finding Study to Assess Efficacy and Safety of Multiple Dose Levels of Inhaled AZD8630 Given Once Daily for 12 Weeks in Adults With Uncontrolled Asthma at Risk of Exacerbations (LEVANTE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-07-31
Enrollment: 516
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel-group treatment study with 4 arms that is patient and Investigator blinded. Patients will be randomly assigned in a 1:1:1:1 ratio to one of the 4 treatment arms.
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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

Eligibility 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

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

5. Pre-BD FEV1 ≥ 40%

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

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

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

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

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

13. 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).

Primary outcomes:
measure: Time to first CompEx Asthma event
timeFrame: 12 weeks
Secondary outcomes:
measure: Pre-BD FEV1
timeFrame: 12 weeks
measure: ACQ-6:
timeFrame: 12 weeks
measure: AQLQ12+
timeFrame: 12 weeks
measure: SGRQ
timeFrame: 12 weeks
measure: FeNO
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Laguna Niguel
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
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city: Long Beach
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city: San Diego
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city: San Jose
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city: Aurora
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city: Englewood
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city: New Haven
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state: Connecticut
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city: Jacksonville
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city: Methuen
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city: Detroit
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city: Monroe
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city: Raleigh
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city: Lima
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city: Austin
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city: American Fork
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city: Roy
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city: Alberdi
country: Argentina
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city: Caba
country: Argentina
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city: Capital Federal
country: Argentina
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city: Florencio Varela
country: Argentina
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city: Mar del Plata
country: Argentina
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city: Quilmes
country: Argentina
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city: Rosario
country: Argentina
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city: San Fernando
country: Argentina
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city: San Miguel de Tucuman
country: Argentina
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city: Duffel
country: Belgium
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city: Mechelen
country: Belgium
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city: Namur
country: Belgium
facility: Research Site
city: Chile
country: Chile
facility: Research Site
city: Curico
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Talca
country: Chile
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city: Viña del Mar
country: Chile
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city: Baotou
country: China
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city: Changchun
country: China
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city: Chifeng
country: China
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city: Chongqing
country: China
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country: China
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city: Guiyang
country: China
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city: Hangzhou
country: China
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country: China
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country: China
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city: Jinan
country: China
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city: Lanzhou
country: China
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city: Nanchang
country: China
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city: Ningbo
country: China
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city: Qingdao
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: ShiJiazhuang
country: China
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city: Taiyuan
country: China
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city: Wenzhou
country: China
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city: Xi'an
country: China
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city: Xuzhou
country: China
facility: Research Site
city: Brno
country: Czechia
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city: Hradec Králové
country: Czechia
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city: Jindrichuv Hradec
country: Czechia
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city: Kralupy nad Vltavou
country: Czechia
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city: Plzeň
country: Czechia
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city: Praha 16
country: Czechia
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country: Czechia
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city: Aalborg
country: Denmark
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city: Aarhus
country: Denmark
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city: Hvidovre
country: Denmark
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city: København NV
country: Denmark
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city: Odense
country: Denmark
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country: Denmark
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city: Vejle
country: Denmark
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city: Lyon Cedex 04
country: France
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country: France
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city: Nice Cedex 01
country: France
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country: France
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country: France
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Hong Kong
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country: Israel
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country: Israel
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country: Israel
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city: Genoa
country: Italy
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city: Milano
country: Italy
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city: Roma
country: Italy
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country: Italy
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city: Chuo-ku
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Kitakyusyu
country: Japan
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city: Kusatsu-shi
country: Japan
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country: Japan
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city: Maebashi
country: Japan
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city: Meguro-ku
country: Japan
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city: Mizunami-shi
country: Japan
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city: Nankoku-shi
country: Japan
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city: Niigata-shi
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
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city: Sapporo-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Benito Juarez
country: Mexico
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country: Mexico
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country: Mexico
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country: Mexico
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city: Monterrey
country: Mexico
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city: Monterrey
country: Mexico
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city: Mérida
country: Mexico
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city: San Juan del Rio
country: Mexico
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city: Villahermosa
country: Mexico
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city: Alkmaar
country: Netherlands
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city: Amersfoort
country: Netherlands
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city: Kezmarok
country: Slovakia
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city: Kosice
country: Slovakia
facility: Research Site
city: Levice
country: Slovakia
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city: Levice
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Topolcany
country: Slovakia
facility: Research Site
city: Topoľčany
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Observatory
country: South Africa
facility: Research Site
city: Somerset West
country: South Africa
facility: Research Site
city: Tygervalley
country: South Africa
facility: Research Site
city: Umkomaas
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Benalmádena
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Kırıkkale
country: Turkey
facility: Research Site
city: Mersin
country: Turkey
facility: Research Site
city: Chernivtsі
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: Portsmouth
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Univeristy of Michigan Hospital, Ann Arbor, MI, US
name: Njira Lugogo
role: PRINCIPAL_INVESTIGATOR
References: