NCT02238483

A Phase IIa Study to Investigate the Efficacy and Safety of AZD7624 in Chronic Obstructive Pulmonary Disease (COPD) Patients While on Maintenance Therapy

Completed Phase 2 Results posted Last updated 24 May 2018

What this trial tests

Phase 2 trial testing AZD7624 1.0 mg in Chronic Obstructive Pulmonary Disease COPD in 213 participants. Completed in 4 April 2016.

Timeline

28 October 2014

Primary endpoint
4 April 2016

4 April 2016

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	213
Start date	28 October 2014
Primary completion	4 April 2016
Estimated completion	4 April 2016
Sites	41 locations across South Africa, Netherlands, Peru, Chile, Argentina, United States

Drugs / interventions tested

• AZD7624 1.0 mg — full drug profile →
• Placebo

Conditions studied

• Chronic Obstructive Pulmonary Disease COPD — all drugs for Chronic Obstructive Pulmonary Disease COPD →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 40 to 85, any sex, with Chronic Obstructive Pulmonary Disease COPD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to First Moderate to Severe COPD Exacerbation or Early Drop-out Related to Worsening of COPD Symptoms Primary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

Group	Value	95% CI
AZD7624	NA	5 – NA
Placebo	118.0	4 – NA

Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs Related to Worsening of COPD Symptoms (i.e. Composite Endpoint, ExDo) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1).

Group	Value	95% CI
AZD7624	2.16	± 0.80
Placebo	1.62	± 0.63

Time to First Event of Moderate or Severe COPD Exacerbations or Early Drop-out (Including Drop-outs Due to Any Cause) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

Group	Value	95% CI
AZD7624	NA	5 – NA
Placebo	118.0	4 – NA

Annual Event Rate of Moderate and Severe COPD Exacerbations and Early Drop-outs (Including Drop-outs Due to Any Cause) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

For the production of summary statistics, the annual event rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Event Rate = No. of Events\*365.25 / (Follow-up date - Date of randomization + 1).

Group	Value	95% CI
AZD7624	2.17	± 0.80
Placebo	1.55	± 0.60

Time to First Moderate or Severe Exacerbation Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

Group	Value	95% CI
AZD7624	NA	5 – NA
Placebo	NA	4 – NA

Annual Exacerbation Rate of Moderate and Severe Exacerbations Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).

Group	Value	95% CI
AZD7624	2.12	± 0.78
Placebo	1.42	± 0.56

Time to First Moderate or Severe Exacerbation (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

Group	Value	95% CI
AZD7624	NA	6 – NA
Placebo	NA	4 – NA

Annual Exacerbation Rate of Moderate and Severe Exacerbations (Where Worsening of COPD Symptoms is Defined as Anthonisens Criteria Fulfilled) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).

Group	Value	95% CI
AZD7624	1.23	± 0.39
Placebo	1.09	± 0.37

Time to First Symptom Defined Exacerbation (as Defined by the Exacerbation of Chronic Pulmonary Disease Tool [EXACT] Daily Diary) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

Group	Value	95% CI
AZD7624	NA	3 – NA
Placebo	NA	2 – NA

Annual Exacerbation Rate of Symptom Defined Exacerbations (as Defined by the EXACT Daily Diary) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

For the production of summary statistics, the annual exacerbation rate per subject is calculated, and standardized per a 52-week period according to the formula described below. Annual Exacerbation Rate = No. of Exacerbations\*365.25 / (Follow-up date - Date of randomization + 1).

Group	Value	95% CI
AZD7624	1.96	± 0.54
Placebo	2.33	± 0.64

Symptoms of COPD (Using the EXACT for Respiratory Symptoms [E-RS] Total Score, a Subset of Items From the EXACT Diary) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

The EXACT for Respiratory Symptoms (E-RS) scale is a derivative instrument comprising a subset of 11 of the EXACT items to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.

Group	Value	95% CI
AZD7624	-0.21	± 0.88
Placebo	0.17	± 0.91

Health Related Quality of Life (as Assessed by St Georges Respiratory Questionnaire for COPD Patients [SGRQ-C]) Secondary · Up to Week 12 treatment discontinuation visit (in some patients this visit was delayed beyond the planned Day 84, up to maximum of 118 days)

The SGRQ-C is a modified version of the St. George's Respiratory Questionnaire, which has been developed to measure the impact of respiratory disease on health status. The SGRQ-C includes 14 questions in 3 domains: symptoms; activity; and impacts. Scores range from 0 to 100 with higher scores indicating benefit. Change in total score from pre study-treatment baseline to Week 12 end of treatment visit are reported.

Group	Value	95% CI
AZD7624	-4.03	± 19.574
Placebo	-5.11	± 17.809

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs) were collected from informed consent throughout the study until follow-up (Week 14). Adverse events (AEs) were collected from Visit 2 (start of OCS treatment) throughout the study until follow-up (Week 14).. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD7624

Serious: 11/108 (10%)

Deaths: —

Placebo

Serious: 11/105 (10%)

Deaths: —

Serious adverse events (12 terms)

Reaction	System	AZD7624	Placebo
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Angina unstable	Cardiac disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Coronary artery occlusion	Cardiac disorders	—	—
Biliary colic	Hepatobiliary disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Urosepsis	Infections and infestations	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—
Syncope	Nervous system disorders	—	—

Other adverse events (15 terms — click to expand)

Reaction	System	AZD7624	Placebo
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Influenza	Infections and infestations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Bronchitis	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Asthenia	General disorders	—	—
Fatigue	General disorders	—	—
Hypertension	Vascular disorders	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—
Sinusitis	Infections and infestations	—	—
Oedema peripheral	General disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Chronic obstructive pulmonary disease, Angina unstable, Cardiac arrest, Coronary artery occlusion, Biliary colic, Cholelithiasis, Back pain, Musculoskeletal chest pain.

Data from ClinicalTrials.gov NCT02238483 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether AZD7624 can reduce acute Chronic Obstructive Pulmonary Disease (COPD) exacerbations in patients on COPD maintenance therapy with a history of frequent acute exacerbations.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel approaches to the management of noneosinophilic asthma.
   Thomson NC. · · 2016 · cited 82× · PMID 26929306 · DOI 10.1177/1753465816632638
2. Atypical p38 Signaling, Activation, and Implications for Disease.
   Burton JC, Antoniades W, Okalova J, Roos MM, et al · · 2021 · cited 52× · PMID 33920735 · DOI 10.3390/ijms22084183
3. The development of AZD7624 for prevention of exacerbations in COPD: a randomized controlled trial.
   Patel NR, Cunoosamy DM, Fagerås M, Taib Z, et al · · 2018 · cited 37× · PMID 29628759 · DOI 10.2147/copd.s150576
4. Emerging pharmaceutical therapies for COPD.
   Lakshmi SP, Reddy AT, Reddy RC. · · 2017 · cited 35× · PMID 28790817 · DOI 10.2147/copd.s121416
5. p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.
   Ahmadi A, Ahrari S, Salimian J, Salehi Z, et al · · 2023 · cited 25× · PMID 37919729 · DOI 10.1186/s12964-023-01337-4
6. Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects.
   Xu Y, Thakur A, Zhang Y, Foged C. · · 2021 · cited 24× · PMID 33525500 · DOI 10.3390/pharmaceutics13020177
7. Kinase inhibitors in the treatment of obstructive pulmonary diseases.
   Defnet AE, Hasday JD, Shapiro P. · · 2020 · cited 17× · PMID 32361678 · DOI 10.1016/j.coph.2020.03.005
8. The COPD Pipeline XXXII.
   Gross N. · · 2016 · cited 1× · PMID 28848893 · DOI 10.15326/jcopdf.3.3.2016.0150