FRONTIER-4: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04631016

Collaborator

(none)

144

Enrollment

126

Locations

Arms

31.3

Anticipated Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult subjects with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD) Chronic Bronchitis	Biological: MEDI3506 Other: Placebo	Phase 2

Detailed Description

Study D9180C00002 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy and safety of MEDI3506 in adult participants with moderate to severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Approximately 100 sites globally will participate in this study. Approximately 144 participants will be randomized to 2 treatment groups in a 1:1 ratio to receive MEDI3506 or placebo.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomised to recieve either MEDI3506 or placebo.Participants will be randomised to recieve either MEDI3506 or placebo.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Investigational product only will be prepared and administrated by unmasked personnel.

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of MEDI3506 in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis (FRONTIER 4)

Actual Study Start Date :

Dec 14, 2020

Anticipated Primary Completion Date :

Jul 24, 2023

Anticipated Study Completion Date :

Jul 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI3506 Approximately 72 participants will be randomized to receive MEDI3506	Biological: MEDI3506 Dose 1
Placebo Comparator: Placebo Approximately 72 participants will be randomized to receive placebo	Other: Placebo Dose 1

Arm

Intervention/Treatment

Experimental: MEDI3506

Approximately 72 participants will be randomized to receive MEDI3506

Biological: MEDI3506

Dose 1

Placebo Comparator: Placebo

Approximately 72 participants will be randomized to receive placebo

Other: Placebo

Dose 1

Outcome Measures

Primary Outcome Measures

Change from baseline to Week 12 in pre-bronchdilator forced expiratory volume in 1 second (FEV1) measured in clinic. [From Baseline to Week 12]
To assess the effects of MEDI3506 compared with placebo on pulmonary function in participants with COPD and chronic bronchitis.

Secondary Outcome Measures

Area under the PK concentration- time curve, during the intervention and follow up periods. [From Study Day 1 to Week 36]
To assess the PK of MEDI3506 in participants with COPD and chronic bronchitis.
Peak plasma concentration (Cmax) profile during the intervention and follow up periods [From Study Day 1 to Week 36]
To assess the PK of MEDI3506 in participants with COPD and chronic bronchitis.
Anti-drug antibodies during the intervention and follow-up periods. [From Study Day 1 to Week 36]
To assess the immunogenicity of MEDI3506 compared with placebo in participants with COPD and chronic bronchitis.
Time to first COPDCompEx event based on the period from baseline to 4 weeks after last dose (Week 28) [From Baseline to Week 28]
To assess the effect of MEDI3506 on COPDCompEx event in participants with COPD and chronic bronchitis
Change from baseline to Week 12 in E-RS:COPD [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score = 0 Max Score= 40
Change from baseline to Week 12 in Mean Breathless, cough and sputum scale (BCSS) Score [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=12
Change from baseline to Week 12 in Cough Visual Analogue Scale (VAS) item [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on respiratory symptoms in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=100
Change from baseline to Week 12 in St Georges Respiratory Questionnaire (SGRQ) total score [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on disease impact in participants with COPD and chronic bronchitis. Higher score indicates worse outcome. Min Score= 0 Max Score=100
Proportion of participants with a decrease in St Georges Respiratory Questionnaire (SGRQ) total score of ≥ 4 points from baseline to Week 12 [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on disease impact in participants with COPD and chronic bronchitis. Responder endpoint 'yes' and 'no'. 'No' is the worse outcome.
Change from baseline to Week 12 in Airway Oscillometry parameter difference between R5 and R20 (R5-R20) [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis.
Change from baseline to Week 12 in Airway Oscillometry parameter Area under Reactance Curve (AX). [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis.
Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 20Hz (R20) . [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis.
Change from baseline to Week 12 in Airway Oscillometry parameter resistance at 5Hz (R5) [From Baseline to Week 12]
To assess the effect of MEDI3506 compared with placebo on airway resistance and reactance in participants with COPD and chronic bronchitis.
At Week 12, ratio to baseline in: Daily (ie, 24 hour) cough frequency, Night time cough frequency, Awake time cough frequency [Week 12]
To evaluate the effect of MEDI3506 compared with placebo on objective cough measures in participants with COPD and chronic bronchitis.
Change from baseline in pre-BD and post-BD FEV1 through Week 28 [From Baseline to Week 28]
To evaluate the effect of MEDI3506 or placebo on lung function by extent of baseline emphysema on CT scan
Change from baseline in pre-BD and post BD FVC through Week 28 [From Baseline to Week 28]
To evaluate the effect of MEDI3506 or placebo on lung function by extent of baseline emphysema on CT scan

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of informed consent
Participant must be 40 to 80 years of age inclusive, at the time of signing the ICF..
Participants who are current or ex-smokers with a tobacco history of ≥ 10 pack-years.
Participants who have a documented history of COPD for at least 1 year.
Participants who have a post-BD FEV1/FVC < 0.70 and a post-BD FEV1 >= 20% and < 80% predicted normal value at screening. Centralized spirometry will be used for this criteria assessment.
Participants who have a physician confirmed participant history of chronic bronchitis as defined as presence of cough and sputum on most days for ≥ 3 months/year in at least the 2 year period immediately prior to SV1(Screening)
Participants who have an average BCSS score of ≥ 2 in cough and ≥ 2 in sputum domains assessed over 14 days preceding SV3
Participants who have a documented stable regimen of dual therapy or triple therapy for ≥ 3 months prior to enrolment; there should have been no change in treatment after the previous exacerbation prior to entering into the study. Where dual therapy consists of ICS + LABA or LABA + LAMA, and triple therapy consists of ICS + LABA + LAMA.
Participants who have a documented history of ≥ 1 moderate or severe AECOPD requiring systemic corticosteroids and/or antibiotics for at least 3 days duration (or 1 injection of depot formulation), or hospitalization for reason of AECOPD in the previous 24 months.
Body mass index within the range 18 to 40 kg/m2 (inclusive).
Female participants of childbearing potential, must have negative pregnancy tests.
Male and female participants must follow protocol contraceptive guidance.

Exclusion Criteria:

Participants with a positive diagnostic nucleic acid test for SARS-CoV-2 at screening. Subjects with mild or asymptomatic disease could be rescreened.
Participants with a significant COVID-19 illness within 6 months of enrolment
As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason which in the investigator's opinion makes it undesirable for the participant to participate in the study.
Current or past diagnosis of asthma which persisted beyond age of 25 years
Clinically important pulmonary disease other than COPD, radiological findings, and/or laboratory findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1 of ≥ 400 mL or ≥ 25% of SV1 FEV1.
Any other clinically relevant abnormal findings on physical examination, laboratory testing; or chest CT scan, which in the opinion of the investigator or medical monitor may compromise the safety of the participant in the study or interfere with evaluation of the study intervention or reduce the participant's ability to participate in the study.

Chest CT scan findings requiring further investigation or repeat CT surveillance before SV14

A family history of heart failure.
A LVEF < 45% measured by echocardiogram.
History of a clinically significant infection (viral, bacterial, or fungal) within 4 weeks.
History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past 2 years prior to screening.
Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV.
Evidence of active or untreated latent TB.
Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up.
Participants currently receiving background therapy that is not approved by regulatory authorities in the country of study for COPD are not eligible for the study.
History of treatment with cardiotoxic medications (eg, as part of cancer therapy) including thiazolidinedione's.
Treatment with broad spectrum antibiotic within 4 weeks prior to randomization (Day 1).
Receiving any of the prohibited concomitant medications as specified in the CSP.
Inability to perform technically acceptable spirometry.

Additional inclusion and exclusion criteria's applies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Sheffield	Alabama	United States	35660
2	Research Site	Tucson	Arizona	United States	85724
3	Research Site	Newport Beach	California	United States	92663
4	Research Site	Westminster	California	United States	92683
5	Research Site	Denver	Colorado	United States	80206
6	Research Site	Newark	Delaware	United States	19713
7	Research Site	Clearwater	Florida	United States	33765
8	Research Site	Kissimmee	Florida	United States	34746
9	Research Site	Ormond Beach	Florida	United States	32174
10	Research Site	Winter Park	Florida	United States	32789
11	Research Site	Lakeside Park	Kentucky	United States	41017
12	Research Site	White Marsh	Maryland	United States	21162
13	Research Site	Ann Arbor	Michigan	United States	48197
14	Research Site	New Bern	North Carolina	United States	28562
15	Research Site	Columbus	Ohio	United States	43215
16	Research Site	Oklahoma City	Oklahoma	United States	73120
17	Research Site	Medford	Oregon	United States	97504
18	Research Site	Philadelphia	Pennsylvania	United States	19140
19	Research Site	Pittsburgh	Pennsylvania	United States	15212
20	Research Site	Pittsburgh	Pennsylvania	United States	15213
21	Research Site	Clinton	South Carolina	United States	29325
22	Research Site	North Charleston	South Carolina	United States	29406
23	Research Site	Spartanburg	South Carolina	United States	29303
24	Research Site	Boerne	Texas	United States	78006
25	Research Site	Richmond	Virginia	United States	23298
26	Research Site	Everett	Washington	United States	98208
27	Research Site	Vancouver	Washington	United States	98664
28	Research Site	Nedlands		Australia	6009
29	Research Site	South Brisbane		Australia	4101
30	Research Site	Spearwood		Australia	6163
31	Research Site	Tarragindi		Australia	4121
32	Research Site	Calgary	Alberta	Canada	T2N 4Z6
33	Research Site	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
34	Research Site	Ajax	Ontario	Canada	L1S 2J5
35	Research Site	Newmarket	Ontario	Canada	L3Y 5G8
36	Research Site	Montreal	Quebec	Canada	H1M 1B1
37	Research Site	Montreal	Quebec	Canada	H4A 3J1
38	Research Site	Sherbrooke	Quebec	Canada	J1L 0H8
39	Research Site	Trois-Rivières	Quebec	Canada	G8T 7A1
40	Research Site	Saskatoon	Saskatchewan	Canada	S7N 0W8
41	Research Site	Quebec		Canada	G1G 3Y8
42	Research Site	Quebec		Canada	G1N 4V3
43	Research Site	Quebec		Canada	G2J 0C4
44	Research Site	Brno		Czechia	625 00
45	Research Site	Olomouc		Czechia	775 21
46	Research Site	Pisek		Czechia	397 01
47	Research Site	Praha 4		Czechia	140 46
48	Research Site	Rokycany		Czechia	337 22
49	Research Site	Hvidovre		Denmark	2650
50	Research Site	København NV		Denmark	2400
51	Research Site	Naestved		Denmark	4700
52	Research Site	Odense C		Denmark	5000
53	Research Site	Vejle		Denmark	7100
54	Research Site	Ålborg		Denmark	9000
55	Research Site	Bamberg		Germany	96049
56	Research Site	Berlin		Germany	10717
57	Research Site	Berlin		Germany	13187
58	Research Site	Darmstadt		Germany	64283
59	Research Site	Hannover		Germany	D-30173
60	Research Site	Leipzig		Germany	04107
61	Research Site	Mainz		Germany	55128
62	Research Site	Marburg		Germany	35037
63	Research Site	Balassagyarmat		Hungary	2660
64	Research Site	Budapest		Hungary	1033
65	Research Site	Debrecen		Hungary	4032
66	Research Site	Edelény		Hungary	3780
67	Research Site	Farkasgyepü		Hungary	8582
68	Research Site	Gödöllő		Hungary	2100
69	Research Site	Hajdúnánás		Hungary	4080
70	Research Site	Pécs		Hungary	7635
71	Research Site	Tatabánya		Hungary	2800
72	Research Site	Ashkelon		Israel	7830604
73	Research Site	Haifa		Israel	34362
74	Research Site	Jerusalem		Israel	91031
75	Research Site	Jerusalem		Israel	91120
76	Research Site	Rehovot		Israel	7661041
77	Research Site	Breda		Netherlands	4818 CK
78	Research Site	Eindhoven		Netherlands	5623EJ
79	Research Site	Heerlen		Netherlands	6419 PC
80	Research Site	Rotterdam		Netherlands	3045 PM
81	Research Site	Rotterdam		Netherlands	3083 AN
82	Research Site	Zutphen		Netherlands	7207 AE
83	Research Site	Auckland		New Zealand	0626
84	Research Site	Christchurch		New Zealand	8013
85	Research Site	Tauranga		New Zealand	3110
86	Research Site	Wellington		New Zealand	6021
87	Research Site	Białystok		Poland	15-044
88	Research Site	Bydgoszcz		Poland	85-079
89	Research Site	Katowice		Poland	40-648
90	Research Site	Krakow		Poland	31-501
91	Research Site	Poznań		Poland	60-693
92	Research Site	Rzeszów		Poland	35-051
93	Research Site	Tarnów		Poland	33-100
94	Research Site	Wroclaw		Poland	54-239
95	Research Site	Wrocław		Poland	50-981
96	Research Site	Bellville		South Africa	7530
97	Research Site	Cape Town		South Africa	7700
98	Research Site	Cape Town		South Africa	7764
99	Research Site	Durban		South Africa	4001
100	Research Site	Johannesburg		South Africa	2113
101	Research Site	Panorama		South Africa	7500
102	Research Site	Alzira		Spain	46600
103	Research Site	L'Hospitalet de Llobregat		Spain	08907
104	Research Site	Laredo		Spain	39770
105	Research Site	Madrid		Spain	28007
106	Research Site	Málaga		Spain	29010
107	Research Site	Mérida		Spain	06800
108	Research Site	Salamanca		Spain	37007
109	Research Site	Santander		Spain	39010
110	Research Site	Zaragoza		Spain	50009
111	Research Site	Changhua		Taiwan	50006
112	Research Site	Kaohsiung		Taiwan	807
113	Research Site	Kaohsiung		Taiwan	83301
114	Research Site	Keelung		Taiwan	20448
115	Research Site	Taipei City		Taiwan	110
116	Research Site	Taipei City		Taiwan	114
117	Research Site	Taipei		Taiwan	235
118	Research Site	Taoyuan City		Taiwan	333
119	Research Site	Bradford		United Kingdom	BD9 6RJ
120	Research Site	Bristol		United Kingdom	BS105NB
121	Research Site	Edinburgh		United Kingdom	EH16 4SA
122	Research Site	London		United Kingdom	EC1A 7BE
123	Research Site	Newcastle-Upon-Tyne		United Kingdom	NE7 7DN
124	Research Site	Watford		United Kingdom	WD18 0HB
125	Research Site	Wishaw		United Kingdom	ML2 0DP
126	Research Site	Wythenshawe		United Kingdom	M23 9QZ