FRONTIER-3: Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04570657

Collaborator

(none)

228

Enrollment

100

Locations

Arms

Anticipated Duration (Months)

2.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study D9181C00001 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of MEDI3506 in adult participants with uncontrolled moderate to severe asthma on standard of care (SOC). Up to approximately 80 sites globally will participate in this study.

Approximately 228 participants will be randomized to 3 treatment groups in a 1:1:1 ratio to receive MEDI3506 dose 1, MEDI3506 dose 2, or placebo.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: MEDI3506 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

228 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MEDI3506 in Adult Participants With Uncontrolled Moderate-to-severe Asthma

Actual Study Start Date :

Sep 16, 2020

Anticipated Primary Completion Date :

Dec 21, 2022

Anticipated Study Completion Date :

Feb 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI3506 Dose 1 Approximately 76 participants will be randomized to this arm to receive the higher dose of MEDI3506	Biological: MEDI3506 Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2
Experimental: MEDI3506 Dose 2 Approximately 76 participants will be randomized to this arm to receive the lower dose of MEDI3506	Biological: MEDI3506 Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2
Placebo Comparator: Placebo Approximately 76 participants will be randomized to this arm. Participants in this group will receive the placebo.	Drug: Placebo Participants will receive multiple doses of placebo

Arm

Intervention/Treatment

Experimental: MEDI3506 Dose 1

Approximately 76 participants will be randomized to this arm to receive the higher dose of MEDI3506

Biological: MEDI3506

Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2

Experimental: MEDI3506 Dose 2

Approximately 76 participants will be randomized to this arm to receive the lower dose of MEDI3506

Biological: MEDI3506

Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2

Placebo Comparator: Placebo

Approximately 76 participants will be randomized to this arm. Participants in this group will receive the placebo.

Drug: Placebo

Participants will receive multiple doses of placebo

Outcome Measures

Primary Outcome Measures

Change from baseline to Week 16 in pre-BD FEV1 (L) [From Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on lung function (pre-BD FEV1 [L]) between baseline and week 16, in adult participants with uncontrolled moderate-to-severe asthma.

Secondary Outcome Measures

Serum MEDI3506 concentration-time profiles from Study Day 1 until Study Day 169 [from Study Day 1 to Study Day 169 for a total of 24 weeks]
MEDI3506 serum concentrations by treatment [ Time Frame: from study Day 1 to Study Day 169] Serum samples will be collected on Day 1(predose), Day 8, as a trough sample collected prior to the next dose administration (on Days 29,57, 85 and 113) and two additional timepoints after last dose (Days 141 and 161)
ADA during the intervention and follow-up periods [from Study Day 1 to Study Day 169 for a total of 24 weeks]
1. To assess immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to severe asthma determined by prevalence of antidrug antibodies (ADA) [ Time Frame: from study Day 1 to Study Day 169] Immunogenicity prevalence measured as number of participants with ADA positive at baseline and/or post-baseline 1. To assess immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to severe asthma determined by incidence of antidrug antibodies (ADA)[ Time Frame: from study Day 1 to Study Day 169] Immunogenicity incidence measured as number of participants with positive treatment emergent ADA
Change from baseline to Week 16 in ACQ-6 score. [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control.
Proportion of participants with a decrease in ACQ-6 score of ≥ 0.5 from baseline to Week 16 [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control.
Proportion of participants achieving ACQ-6 well controlled status (defined as ACQ-6 score ≤ 0.75 at Week 16) [Week 16]
To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control.
Change from baseline in SGRQ at Week 16 [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. SGRQ = St George's Respiratory Questionnaire. Minimum score = 0. Maximum score = 100. A higher score indicates a worse health status.
Proportion of participants with a decrease in SGRQ total score of ≥ 4 points from baseline to Week 16. [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. SGRQ = St George's Respiratory Questionnaire. Minimum score = 0. Maximum score = 100. A higher score indicates a worse health status.
Change from baseline to Weeks 8 and 16 in post-BD FEV1 (L) [From baseline to Weeks 8 and 16]
To further assess the effect of MEDI3506 compared with placebo on lung function (post-BD FEV1 [L]) between baseline and weeks 8 and 16, in adult participants with uncontrolled moderate-to-severe asthma
Time to first CompEx event based on the period from baseline to Week 16 [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma
Annualised CompEx event rate [Baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma.
Percent change from baseline to Week 16 in concentration of FeNO in exhaled breath [From baseline to Week 16]
To assess the effect of MEDI3506 compared with placebo on concentration of FeNO in adult participants with uncontrolled moderate-to-severe asthma

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA

Aged 18 to < 65 years of age
Physician-diagnosed asthma of early onset, defined as development of asthma before the age of 25 years.
History of ≥ 1 asthma exacerbation in previous 24 months
Treated with medium to high dose ICS defined as total daily dose of > 250 g fluticasone dry powder or equivalent, for at least 12 months and on a stable dose for ≥ 3 months.
Stable LABA therapy for ≥ 3 months.
An ACQ-6 score ≥ 1.5.
Morning pre-BD FEV1 ≥ 40% predicted normal and > 1 L.
Morning pre-BD FEV1 < 85% predicted normal.
Participants with documented evidence of asthma as demonstrated by either:
BD reversibility, within 12 months, or at screening, or
Positive methacholine challenge test within 12 months.
Bodyweight ≥ 40 kg and BMI < 40 kg/m2.
For female participants, a negative pregnancy test.
Abide by contraception requirements for males and females
Provide informed consent

EXCLUSION CRITERIA

Participants with a positive diagnostic nucleic acid test for SARS-CoV-2.
Participants with a significant COVID-19 illness within 6 months of enrolment:
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 latent TB:
An LVEF < 45% measured by echocardiogram during screening.
A family history of heart failure.
Current smokers or recent ex-smokers i.e., have quit e cigarettes or other inhaled tobacco products ≤ 6 months prior to SV1.
Ex-smokers with a total smoking history of > 10 pack years.
As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason (prior to randomisation) that in the investigator's opinion makes it undesirable for the participant to participate in the study.
Any clinically important pulmonary disease other than asthma.
Any other clinically relevant abnormal findings on physical examination or laboratory testing, that in the opinion of the investigator or medical monitor might compromise the safety of the participant in the study or interfere with evaluation of the study intervention.
A known history of severe reaction to any medication including biologic agents or human gamma globulin therapy.
History of, or a reason to believe, a participant has a history of, drug or alcohol abuse within the past 2 years.
Current diagnosis of cancer.
History of cancer, except if treated with apparent success with curative therapy (response duration of > 5 years).
History of allogeneic bone marrow transplant.
A helminth parasitic infection diagnosed within 6 months prior to SV4 (randomisation) that has not been treated, or has not responded to SOC therapy.
An asthma exacerbation within 8 weeks.
Receiving any prohibited concomitant medications or therapies as specified in the protocol:

Known history of allergy or reaction to any component of the study intervention formulation, including hereditary fructose intolerance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Little Rock	Arkansas	United States	72205
2	Research Site	Anaheim	California	United States	92801
3	Research Site	Bakersfield	California	United States	93301
4	Research Site	Los Angeles	California	United States	90025
5	Research Site	Newport Beach	California	United States	92663
6	Research Site	Aurora	Colorado	United States	80012
7	Research Site	Denver	Colorado	United States	80230
8	Research Site	Coral Gables	Florida	United States	33134
9	Research Site	Coral Gables	Florida	United States	33134
10	Research Site	Saint Petersburg	Florida	United States	33707
11	Research Site	Ames	Iowa	United States	50010-3014
12	Research Site	Missoula	Montana	United States	59808
13	Research Site	Charlotte	North Carolina	United States	28277
14	Research Site	Dublin	Ohio	United States	43016
15	Research Site	Toledo	Ohio	United States	43617
16	Research Site	Edmond	Oklahoma	United States	73034
17	Research Site	Medford	Oregon	United States	97504
18	Research Site	Greenville	South Carolina	United States	29607
19	Research Site	Spartanburg	South Carolina	United States	29303
20	Research Site	Boerne	Texas	United States	78006
21	Research Site	Buenos Aires		Argentina	C1121 ABE
22	Research Site	Buenos Aires		Argentina	C1414AIF
23	Research Site	Caba		Argentina	C1425BEN
24	Research Site	Cordoba		Argentina	X5003DCE
25	Research Site	Florencio Varela		Argentina	1888
26	Research Site	Florida		Argentina	B1602DQD
27	Research Site	Godoy Cruz		Argentina	5501
28	Research Site	Lanus Este		Argentina	B1824KAJ
29	Research Site	Mar del Plata		Argentina	7600
30	Research Site	Mendoza		Argentina	5500
31	Research Site	Mendoza		Argentina	M5500GHB
32	Research Site	Quilmes		Argentina	B1878FNR
33	Research Site	San Miguel de Tucuman		Argentina	T4000IAQ
34	Research Site	Calgary	Alberta	Canada	T6G 2C8
35	Research Site	Edmonton	Alberta	Canada	T6G 2C8
36	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
37	Research Site	Vancouver	British Columbia	Canada	V6Z 1Y6
38	Research Site	Hamilton	Ontario	Canada	L8N 3Z5
39	Research Site	Hamilton	Ontario	Canada	L8N 4A6
40	Research Site	Pierrefonds	Quebec	Canada	H9H 4Y6
41	Research Site	Saskatoon	Saskatchewan	Canada	S7N 0W8
42	Research Site	Quebec		Canada	G1V4G5
43	Research Site	Berlin		Germany	10717
44	Research Site	Berlin		Germany	10787
45	Research Site	Berlin		Germany	12203
46	Research Site	Cottbus		Germany	03050
47	Research Site	Dresden		Germany	01069
48	Research Site	Frankfurt/Main		Germany	60389
49	Research Site	Frankfurt		Germany	60596
50	Research Site	Hamburg		Germany	22143
51	Research Site	Karlsruhe		Germany	76137
52	Research Site	Koblenz		Germany	56068
53	Research Site	Landsberg		Germany	86899
54	Research Site	Leipzig		Germany	04357
55	Research Site	Lübeck		Germany	23552
56	Research Site	Magdeburg		Germany	39120
57	Research Site	Mainz		Germany	55128
58	Research Site	Peine		Germany	31224
59	Research Site	Schwerin		Germany	19055
60	Research Site	Wiesbaden		Germany	65187
61	Research Site	Balassagyarmat		Hungary	2660
62	Research Site	Budapest		Hungary	1033
63	Research Site	Farkasgyepü		Hungary	8582
64	Research Site	Gödöllő		Hungary	2100
65	Research Site	Szeged		Hungary	6722
66	Research Site	Százhalombatta		Hungary	2440
67	Research Site	Białystok		Poland	15-044
68	Research Site	Białystok		Poland	15-540
69	Research Site	Bychawa		Poland	23100
70	Research Site	Bydgoszcz		Poland	85-231
71	Research Site	Katowice		Poland	40-648
72	Research Site	Krakow		Poland	30-033
73	Research Site	Lodz		Poland	90-302
74	Research Site	Lublin		Poland	20-362
75	Research Site	Poznań		Poland	60-214
76	Research Site	Swidnica		Poland	58-100
77	Research Site	Tarnów		Poland	33-100
78	Research Site	Wroclaw		Poland	51-162
79	Research Site	Wroclaw		Poland	54-239
80	Research Site	Wrocław		Poland	53-301
81	Research Site	Bellville		South Africa	7530
82	Research Site	Benoni		South Africa	1500
83	Research Site	Bloemfontein		South Africa	9301
84	Research Site	Bloemfontein		South Africa	9301
85	Research Site	Cape Town		South Africa	7500
86	Research Site	Cape Town		South Africa	7572
87	Research Site	Cape Town		South Africa	7700
88	Research Site	Durban		South Africa	4001
89	Research Site	Durban		South Africa	4091
90	Research Site	Johannesburg		South Africa	2113
91	Research Site	Kempton Park		South Africa	1619
92	Research Site	Middelburg		South Africa	1055
93	Research Site	Pretoria		South Africa	0002
94	Research Site	Welkom		South Africa	9460
95	Research Site	Birmingham		United Kingdom	B9 5SS
96	Research Site	Bradford		United Kingdom	BD9 6RJ
97	Research Site	Cambridge		United Kingdom	CB2 0QQ
98	Research Site	High Wycombe		United Kingdom	HP11 2QW
99	Research Site	London		United Kingdom	W1T 6AH
100	Research Site	Oxford		United Kingdom	0X3 7LE

Sponsors and Collaborators

AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT04570657

Other Study ID Numbers:

D9181C00001
2020-000789-40
140910

First Posted:

Sep 30, 2020

Last Update Posted:

Aug 3, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by AstraZeneca

Additional relevant MeSH terms:

Asthma

Study Results

No Results Posted as of Aug 3, 2022