NCT02753764

Brief Summary

This is a double-blind, placebo controlled 4 week crossover study to investigate the efficacy and safety of AZD7624 (an inhaled p38 inhibitor) in corticosteroid resistant (CR) asthmatics. For the purpose of this study 10 symptomatic CR asthma patients with a FEV1% predicted \<80% and normal bronchodilator response, 10 CS asthmatics and 10 healthy controls will be recruited.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2017

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 18, 2016

Completed
10 days until next milestone

First Posted

Study publicly available on registry

April 28, 2016

Completed
8 months until next milestone

Study Start

First participant enrolled

January 1, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 25, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 25, 2019

Completed
Last Updated

August 21, 2019

Status Verified

August 1, 2019

Enrollment Period

2.2 years

First QC Date

April 18, 2016

Last Update Submit

August 19, 2019

Conditions

Corticosteroid Resistant (CR) Asthmatics

Outcome Measures

Primary Outcomes (2)

  • P38 MAPK activation (as measured by phosphorylation) in the whole blood samples by flow cytometry.

    4 months

  • P38 MAPK activation in the whole blood samples by flow cytometry and p38 MAPK expression in BAL and induced sputum macrophages by immunostaining and microscopy imaging before and after p38 inhibitor treatment vs placebo in CR asthma patients

    Evaluate MAPK activation in the whole blood samples by flow cytometry and pMAPK expression in BAL and induced sputum macrophages by immunostaining and microscopy imaging before and after p38 inhibitor AZD7624 treatment vs placebo.

    4 months

Study Arms (4)

Normal control

NO INTERVENTION

Health volunteers will be recruited as an additional control group.

Corticosteroid sensitive (CS) asthmatics

OTHER

After the initial visit, asthmatics will be given oral prednisone for 1 week and patients will return for the spirometer assessment. Patients will be defined as CR if \<10% improvement in FEV1 % predicted is observed and as CS in \>12% improvement in FEV1% predicted is observed.

Drug: prednisone

Corticosteroid resistant (CR) asthmatics active

ACTIVE COMPARATOR

The study will have a 1 week oral corticosteroid (OSC) run-in period. Subjects unresponsive to OCS will be defined as corticosteroid resistant (CR) and randomized to two crossover treatment sequences consisting of 4 weeks of inhaled AZD7624 or placebo, followed by 4 weeks of a washout period, and another 4 weeks of placebo or ASD7624

Drug: AZD7624Drug: prednisoneDrug: Placebo

Corticosteroid resistant (CR) asthmatics placebo

PLACEBO COMPARATOR

The study will have a 1 week oral corticosteroid (OSC) run-in period. Subjects unresponsive to OCS will be defined as corticosteroid resistant (CR) and randomized to two crossover treatment sequences consisting of 4 weeks of inhaled AZD7624 or placebo, followed by 4 weeks of a washout period, and another 4 weeks of placebo or ASD7624

Drug: AZD7624Drug: prednisoneDrug: Placebo

Interventions

AZD7624DRUG
Corticosteroid resistant (CR) asthmatics activeCorticosteroid resistant (CR) asthmatics placebo
prednisoneDRUG

oral prednisone 20 mg bid for one week

Corticosteroid resistant (CR) asthmatics activeCorticosteroid resistant (CR) asthmatics placeboCorticosteroid sensitive (CS) asthmatics
PlaceboDRUG
Corticosteroid resistant (CR) asthmatics activeCorticosteroid resistant (CR) asthmatics placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Asthmatic Subjects
  • Males and women of non-childbearing potential aged 18-65 of any racial or ethnic background, who are physically and mentally able to cooperate with the proposed tests and procedures and who are able to give informed consent.
  • Asthma defined by symptoms and/or a doctor's diagnosis compatible with asthma as per 2014 GINA Guidelines.
  • Symptomatic patients (ACQ\>1.25) with FEV1 % predicted 80%, currently taking ICS or ICS/LABA. Patients should demonstrate normal bronchodilator response, i.e. there must be equal or greater than 12% or 200ml improvement in FEV1 post-bronchodilator (albuterol).
  • Females must have a negative pregnancy test at Visit 1, must not be lactating and must be of non-childbearing potential, by fulfilling one of the following criteria:
  • Postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all possible exogenous hormonal treatments and luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range (at Visit 1)
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
  • Males must be surgically sterile or agree to use an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of investigational product to prevent pregnancy in a partner.
  • A weight of ≥50 kg (measured at Visit 1)
  • Healthy Controls
  • Subjects must be 18 to 65 years old, who are physically and mentally able to cooperate with the proposed tests and procedures and who are able to give informed consent.
  • They must have no respiratory or cardiac symptoms (cough, phlegm, wheeze, dyspnea) and no physician diagnosed cardiac or respiratory disease.
  • No allergic history.
  • FEV1≥ 80%
  • Females must have a negative pregnancy test at Visit 1, must not be lactating and must be of non-childbearing potential, by fulfilling one of the following criteria:
  • +3 more criteria

You may not qualify if:

  • An FEVl \<60% predicted post albuterol bronchodilator.
  • Oral steroid use within the past 6 weeks.
  • Acute respiratory illness within 6 weeks of the study.
  • Another pulmonary disease expected to affect participation in the study or the measurements to be examined.
  • Pregnancy.
  • Smoking in last year or prior smoking history of more than 10 pack years.
  • Previous randomization to treatment in the present study (at Visit 1)
  • Participation in another clinical study with any novel investigational medicine product within 3 months before the first dose of investigational product in this study (at Visit 4)
  • Previously intake of any p38 inhibitor (same class as AZD7624)
  • Significant disease or disorder other than asthma (e.g. cardiovascular; pulmonary as e.g. tuberculosis and cystic fibrosis; gastrointestinal, liver; neurological; musculoskeletal; endocrine; metabolic; malignant; psychiatric; major physical impairment) which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or influence the results of the study, or the patient's ability to participate in the study (at Visit 1)
  • Any clinically relevant abnormal findings in clinical chemistry, haematology and urinalysis, which, in the opinion of the investigator, may put the patient at risk because of participation in the study (for CR patients only at Visit 3a)
  • Any clinically relevant abnormal findings in physical examination, pulse or blood pressure which, in the opinion of the investigator, may put the patient at risk because of participation in the study (at Visit 1)
  • History or family history of muscle diseases (at Visit 1)
  • Abnormal vital signs, after 10 minutes supine rest, defined as any of the following (CR patients, at Visit 3a):
  • Systolic blood pressure (SBP) above 140 mmHg if \<60 years of age and above 150 mmHg if ≥60 years of age
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

AZD7624Prednisone

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prinicipal Investigator

Study Record Dates

First Submitted

April 18, 2016

First Posted

April 28, 2016

Study Start

January 1, 2017

Primary Completion

February 25, 2019

Study Completion

February 25, 2019

Last Updated

August 21, 2019

Record last verified: 2019-08

Locations

US(1)