Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Adult Patients With Uncontrolled Moderate to Severe Asthma

• Sponsor: Sanofi (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05097287
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 1,828
• Locations: 89
• Arms: 2
• Anticipated Duration (Months): 69.9
• Patients Per Site: 20.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is an interventional, randomized, parallel group, treatment, Phase 3b/4, double blind, 2-arm study to assess the effect of dupilumab compared to standard of care therapy on preventing or slowing the rate of lung function decline in adult patients with uncontrolled moderate to severe asthma.

The estimated duration is 4±1 weeks of screening and run-in period, followed by a 3-year double blinded treatment period. There will be a post-treatment follow-up (FU) period up to 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Dupilumab; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 1828 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Patients With Uncontrolled Moderate to Severe Asthma
• Actual Study Start Date: Dec 16, 2021
• Anticipated Primary Completion Date: Jun 28, 2025
• Anticipated Study Completion Date: Oct 15, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab Dupilumab administered every 2 weeks (Q2W) after an initial loading dose (2 injections) on Day 1	Drug: Dupilumab; solution for injection subcutaneous
Placebo Comparator: Placebo Matching placebo administered Q2W after an initial loading dose (2 injections) on Day 1	Drug: Placebo; solution for injection subcutaneous

Outcome Measures

Primary Outcome Measures

1. Rate of change from week 8 to week 52 on post-BD FEV1 slope in FeNO population [Week 8 to Week 52]

   Rate of change from week 8 to week 52 on post-bronchodilator (BD) forced expiratory volume in one second (FEV1) slope in FeNO population.

Secondary Outcome Measures

1. Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population [Week 8 to Week 52]

   Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population.

2. Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population [Week 8 to Week 104]

   Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population.

3. Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations [Baseline to Week 52]

   Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations.

4. Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations [Baseline to Week 52]

   Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations.

5. Annualized severe exacerbation rate during the 52-week period in FeNO and Total populations [Baseline to Week 52]

   Exacerbation defined as a deterioration of asthma requiring use of systemic corticosteroids for ≥3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids.

6. Change from baseline to week 52 in fractional exhaled nitric oxide (FeNO) levels in FeNO and Total populations [Baseline to Week 52]

   Change from baseline to week 52 in FeNO levels in FeNO and Total populations.

7. Change from baseline to week 52 in Asthma Control Questionnaire 7 items (ACQ-7) in FeNO and Total populations [Baseline to Week 52]

   ACQ-7 was designed to measure both the adequacy of asthma control and change in asthma control. A global score ranges between 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.

8. Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations [Baseline to Week 52]

   Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations.

9. Change from baseline to week 52 in Forced Vital Capacity (FVC) in FeNO and Total populations [Baseline to Week 52]

   Change from baseline to week 52 in FVC in FeNO and Total populations.

10. Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population [Week 8 to Week 104]

    Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population.

11. Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations [Baseline to Week 104]

    Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations.

12. Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations [Baseline to Week 104]

    Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations.

13. Annualized severe exacerbation rate during the 104-week period in FeNO and Total populations [Baseline to Week 104]

    Exacerbation defined as a deterioration of asthma requiring use of systemic corticosteroids for ≥3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids.

14. Change from baseline to week 104 in FeNO levels in FeNO and Total populations [Baseline to Week 104]

    Change from baseline to week 104 in FeNO levels in FeNO and Total populations.

15. Change from baseline to week 104 in ACQ-7 in FeNO and Total populations [Baseline to Week 104]

    ACQ-7 was designed to measure both the adequacy of asthma control and change in asthma control. A global score ranges between 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.

16. Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations [Baseline to Week 104]

    Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations.

17. Change from baseline to week 104 FVC in FeNO and Total populations [Baseline to Week 104]

    Change from baseline to week 104 FVC in FeNO and Total populations.

18. Change from baseline to week 52 in Asthma Quality Of Life Questionnaire with Standardized Activities (AQLQ(S)) in FeNO and Total populations [Baseline to Week 52]

    The AQLQ (S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to patients as a result of their asthma. A global score is calculated ranging from 1 to 7. Higher scores indicate better quality of life.

19. Change from baseline to week 104 in AQLQ(S) in FeNO and Total populations [Baseline to Week 104]

    The AQLQ (S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to patients as a result of their asthma. A global score is calculated ranging from 1 to 7. Higher scores indicate better quality of life.

20. Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations [Week 8 to Week 156]

    Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations.

21. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Baseline to Week 168]

    Incidence of TEAEs and SAEs.

22. Incidence of adverse events of special interest (AESIs) [Baseline to Week 168]

    Incidence of AESIs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant must be at least 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.

• Patients with a physician diagnosis of asthma (according to Global Initiative for Asthma (GINA) 2021) for ≥12 months

• Treatment with medium to high dose inhaled corticosteroids (ICS) (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta-2 adrenergic receptor agonists (LABA), LTRA) with a stable dose ≥1 month prior to Visit 1. Patients requiring a third controller for their asthma will be considered eligible for this study, and it should also be on stable dose ≥1 month prior to Visit 1.

• Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal for adults at Visits 1 and 2, prior to randomization

• Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.

• Bronchodilator reversibility (≥ 12% and 200 mL improvement in FEV1 post short-acting beta agonists (SABA) administration) during the screening period, prior to randomization, unless reversibility test meeting the inclusion criteria was done within 12 months prior to Visit 1.

• FeNO ≥35 ppb at Visit 2, prior to randomization. Up to 550 patients can be enrolled with baseline FeNO<35 ppb at Visit 2

• History of ≥1 severe exacerbation(s) in the previous year before V1 defined as a deterioration of asthma requiring:

• Use of systemic corticosteroids for ≥3 days; or

• Hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids. - - - -

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, emphysema, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome).

• Severe asthma exacerbation requiring treatment with systemic corticosteroid (SCS) in the past month before visit 1 or during the screening period.

• Current acute bronchospasm or status asthmaticus.

• Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated peripheral eosinophil counts.

• Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study. Examples include, but are not limited to, participants with short life expectancy, uncontrolled diabetes, cardiovascular conditions, severe renal conditions (eg, participants on dialysis), or other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in the study documents (chart notes, case report forms [CRFs], etc).

• Patients with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed on a country by country basis, according to local guidelines if required by regulatory authorities or ethics boards, or if TB is suspected by the investigator

• Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.

• Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.

• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals or receiving only symptomatic treatment (e.g. influenza or COVID-19) within 2 weeks before the screening visit (Visit 1) or during the screening period.

• History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).

• Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period

• Current smoker (cigarette or e-cigarette) or cessation of smoking within 6 months prior to Visit 1.

• Previous smoker with a smoking history >10 pack-years.

• History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.

• Any biologic therapy (including experimental treatments and dupilumab) or any other biologic therapy/immunosuppressant/immunomodulators within 4 weeks prior to V1 or 5 half-lives, whichever is longer.

• Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit) or during the screening period.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cullman Research Center, LLC-Site Number:8400001	Cullman	Alabama	United States	35055
2	Syed Research Consultants, LLC-Site Number:8400015	Sheffield	Alabama	United States	35660
3	Del Sol Research Management, LLC-Site Number:8400017	Tucson	Arizona	United States	85712
4	Kern Research, Inc-Site Number:8400037	Bakersfield	California	United States	93301
5	ASCADA Research-Site Number:8400076	Fullerton	California	United States	92835
6	NewportNativeMD, Inc-Site Number:8400054	Newport Beach	California	United States	92663
7	Allianz Research Institute-Site Number:8400018	Westminster	California	United States	92683
8	Central Florida Pulmonary Group, PA-Site Number:8400035	Altamonte Springs	Florida	United States	32701
9	Florida Center for Allergy and Asthma Research-Site Number:8400032	Aventura	Florida	United States	33180
10	Pulmonary & Sleep of Tampa Bay-Site Number:8400046	Brandon	Florida	United States	33511
11	Omega Research-Site Number:8400023	DeBary	Florida	United States	32713
12	Florida Lung, Asthma, and Sleep Specialists-Site Number:8400098	Kissimmee	Florida	United States	34746
13	Floridian Clinical Research-Site Number:8400091	Miami Lakes	Florida	United States	33016
14	Biotech Pharmaceutical Group, LLC-Site Number:8400073	Miami	Florida	United States	33155
15	Ivetmar Medical Group LLC-Site Number:8400063	Miami	Florida	United States	33155
16	Research Institute of South Florida-Site Number:8400079	Miami	Florida	United States	33173
17	HMD Research LLC-Site Number:8400024	Orlando	Florida	United States	32819
18	Alpha Clinical Research Georgia-Site Number:8400116	Atlanta	Georgia	United States	30312
19	Allergy & Asthma Specialists, PSC-Site Number:8400007	Owensboro	Kentucky	United States	42301
20	Avant Research Associates LLC-Site Number:8400117	Crowley	Louisiana	United States	70526
21	Javara Inc-Site Number:8400087	Annapolis	Maryland	United States	21401
22	Allergy Asthma Specialists of Maryland-Site Number:8400119	White Marsh	Maryland	United States	21162
23	Genesis Clinical Research & Consulting-Site Number:8400050	Fall River	Massachusetts	United States	02723
24	University of Michigan-Site Number:8400030	Ann Arbor	Michigan	United States	48109
25	Revival Research Institute, LLC-Site Number:8400097	Dearborn	Michigan	United States	48126
26	Revive Research Institute-Site Number:8400100	Lathrup Village	Michigan	United States	48076
27	Romedica, LLC-Site Number:8400043	Rochester	Michigan	United States	48307
28	Great Lakes Research Institute-Site Number:8400111	Southfield	Michigan	United States	48055
29	Respiratory Medicine Research Institute of Michigan, PLC-Site Number:8400107	Ypsilanti	Michigan	United States	48197
30	Nebraska Medical Research Institute, Inc.-Site Number:8400055	Bellevue	Nebraska	United States	68123
31	Mid Hudson Medical Research PLLC-Site Number:8400031	New Windsor	New York	United States	12553-7754
32	Great Lakes Medical Research-Site Number:8400010	Westfield	New York	United States	14787
33	Tryon Medical Partners-Site Number:8400088	Charlotte	North Carolina	United States	28277
34	Clinical Research of Gastonia-Site Number:8400012	Gastonia	North Carolina	United States	28054
35	Advanced Respiratory and Sleep Medicine-Site Number:8400056	Huntersville	North Carolina	United States	28078
36	Lapis Clinical Research At BlueSkies Family Medicine-Site Number:8400112	Mooresville	North Carolina	United States	28117
37	Toledo Institute of Clinical Research-Site Number:8400051	Toledo	Ohio	United States	43617
38	Vital Prospects Clinical Research Institute, P.C.-Site Number:8400093	Tulsa	Oklahoma	United States	74138
39	Temple Lung Center-Site Number:8400038	Philadelphia	Pennsylvania	United States	19140
40	Allergy & Clinical Immunology Associates-Site Number:8400042	Pittsburgh	Pennsylvania	United States	15241
41	National Allergy and ENT-Site Number:8400092	Charleston	South Carolina	United States	29420
42	Bogan Sleep Consultants-Site Number:8400102	Columbia	South Carolina	United States	29201
43	ADAC Research, PA-Site Number:8400026	Greenville	South Carolina	United States	29607
44	Health Concepts-Site Number:8400006	Rapid City	South Dakota	United States	57702
45	TTS Research-Site Number:8400009	Boerne	Texas	United States	78006
46	C & R Research Services USA-Site Number:8400067	Houston	Texas	United States	77022
47	Biopharma Informatic-Site Number:8400062	Houston	Texas	United States	77043
48	Clear Brook Medical Associates-Site Number:8400080	Houston	Texas	United States	77089
49	Metroplex Pulmonary and Sleep Center-Site Number:8400014	McKinney	Texas	United States	75069
50	Texas Institute of Cardiology-Site Number:8400003	McKinney	Texas	United States	75071
51	DM Clinical Research-Site Number:8400103	Tomball	Texas	United States	77375
52	Eastern Virginia Medical School (EVMS) Medical Group - Otola-Site Number:8400011	Norfolk	Virginia	United States	23507
53	Investigational Site Number :1240010	Moncton	New Brunswick	Canada	E1G 5C4
54	Investigational Site Number :1240018	Niagara Falls	Ontario	Canada	L2H 1H5
55	Investigational Site Number :1240011	Toronto	Ontario	Canada	M5G 1E2
56	Investigational Site Number :1240001	Toronto	Ontario	Canada	M5T 3A9
57	Investigational Site Number :1240007	Toronto	Ontario	Canada	M9V 4B4
58	Investigational Site Number :1240014	Montreal	Quebec	Canada	H1M 1B1
59	Investigational Site Number :1240002	Quebec		Canada	G1G 3Y8
60	Investigational Site Number :1240003	Windsor		Canada	N8X 5A6
61	Investigational Site Number :3000009	Palaio Faliro, Athens		Greece	17562
62	Investigational Site Number :3480004	Hajdúnánás		Hungary	4080
63	Investigational Site Number :3480007	Mosonmagyaróvár		Hungary	9200
64	Investigational Site Number :3480001	Százhalombatta		Hungary	2440
65	Investigational Site Number :4100007	Busan	Busan-gwangyeoksi	Korea, Republic of	602-739
66	Investigational Site Number :4100006	Daegu	Daegu-gwangyeoksi	Korea, Republic of	705-717
67	Investigational Site Number :4100008	Wonju	Gangwon-do	Korea, Republic of	26426
68	Investigational Site Number :4100010	Incheon	Incheon-gwangyeoksi	Korea, Republic of	21431
69	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03080
70	Investigational Site Number :4100009	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03312
71	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	05030
72	Investigational Site Number :4100004	Seoul	Seoul-teukbyeolsi	Korea, Republic of	120-752
73	Investigational Site Number :4100005	Seoul	Seoul-teukbyeolsi	Korea, Republic of	135-710
74	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi	Korea, Republic of	138-878
75	Investigational Site Number :4840002	Guadalajara	Jalisco	Mexico	44100
76	Investigational Site Number :4840001	Durango		Mexico	34000
77	Investigational Site Number :4840005	Monterrey		Mexico	66465
78	Investigational Site Number :4840003	Veracruz		Mexico	91910
79	Investigational Site Number :7030002	Spisska Nova Ves		Slovakia	05201
80	Investigational Site Number :7100006	Benoni		South Africa	1500
81	Investigational Site Number :7100002	Pretoria		South Africa	0009
82	Investigational Site Number :7920007	Ankara		Turkey	06100
83	Investigational Site Number :7920008	Ankara		Turkey	06520
84	Investigational Site Number :7920003	Balcali Adana		Turkey	01330
85	Investigational Site Number :7920001	Istanbul		Turkey	34303
86	Investigational Site Number :7920006	Izmir		Turkey	35100
87	Investigational Site Number :7920004	Kirikkale		Turkey	71450
88	Investigational Site Number :7920002	Mersin		Turkey	33343
89	Investigational Site Number :8260002	Bradford		United Kingdom	BD9 6DA

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05097287
• Other Study ID Numbers: LPS16676; 2021-003903-16
• First Posted: Oct 28, 2021
• Last Update Posted: Jul 13, 2022
• Last Verified: Jul 12, 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: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Jul 13, 2022