MORPHEO: Dupilumab Asthma Sleep Study

• Sponsor: Sanofi (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04502862
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 260
• Locations: 58
• Arms: 2
• Anticipated Duration (Months): 35.2
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To assess the effect of dupilumab on sleep

Secondary Objectives:

• To evaluate the effect of dupilumab on additional patient reported sleep outcomes

• To evaluate the effect of dupilumab on objective sleep assessment

• To evaluate the effect of dupilumab on asthma symptoms

• To evaluate the effect of dupilumab on lung function

• To evaluate the safety of dupilumab

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: SAR231893; Drug: Placebo	Phase 4

Detailed Description

Study duration per participant will be approximately 16 weeks and up to 29 weeks including up to 5 weeks screening period, a 12-week treatment period and up to 12 weeks post-treatment follow-up period

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Interim analysis for sample size re-estimationInterim analysis for sample size re-estimation
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Effect of Dupilumab on Sleep Disturbance in Patients With Uncontrolled Persistent Asthma
• Actual Study Start Date: Aug 10, 2020
• Anticipated Primary Completion Date: Apr 25, 2023
• Anticipated Study Completion Date: Jul 18, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dupilumab 2 x dupilumab injections as loading dose on Day 1, followed by 1 dupilumab maintenance dose injection every 2 weeks (Q2W) during 12 weeks	Drug: SAR231893; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous; Other Names: Dupixent
Placebo Comparator: Placebo 2 x placebo injections on Day 1, then 1 placebo injection Q2W during 12 weeks	Drug: Placebo; Pharmaceutical form: Solution for injection; Route of administration: Subcutaneous

Outcome Measures

Primary Outcome Measures

1. Change in sleep disturbance score in Asthma Sleep Disturbance Questionnaire [Baseline to Week 12]

   Change from baseline to Week 12 in sleep disturbance score using the Asthma Sleep Disturbance Questionnaire

Secondary Outcome Measures

1. Change in the number of nocturnal awakenings in Sleep Diary [Baseline to Week 12]

   Change from baseline to Week 12 in the number of nocturnal awakenings as recorded in Sleep Diary

2. Change in PROMIS sleep-related impairment assessment [Baseline to Week 12]

   Change from baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment 8a scale

3. Change in sleep quality in Sleep Diary [Baseline to Week 12]

   Change from baseline to Week 12 in sleep quality (Sleep Diary)

4. Change in restorative sleep in Sleep Diary [Baseline to Week 12]

   Change from baseline to Week 12 in restorative sleep (Sleep Diary)

5. Change in WASO in Sleep Diary [Baseline to Week 12]

   Change from baseline to Week 12 in wake after sleep onset (WASO) (Sleep Diary)

6. Change in WASO (actigraphy data) [Baseline to Week 12]

   Change from baseline to Week 12 in WASO based on actigraphy data

7. Change in daytime and nighttime asthma symptoms in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) [Baseline to Week 12]

   Change from baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD)

8. Change in pre-bronchodilator (BD) FEV1 [Baseline to Week 12]

   Change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 second (pre-BD FEV1)

9. Incidence of adverse events [Baseline up to Week 24]

   Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESI), including clinically significant changes in vital signs considered to be adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 Guidelines for ≥12 months treated with medium to high dose inhaled corticosteroid (ICS) and a second controller (ie, long-acting beta agonist, leukotriene receptor antagonist). A third controller is allowed but not mandatory. The dose regimen should be stable for at least 1 month before the study and during the screening period

• History of at least one asthma exacerbation within 1 year prior to screening. Exacerbation is defined as deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids (oral or injectable)

• Eosinophils ≥150 cells/μL and fractional exhaled nitric oxide (FeNO) ≥25 ppb during screening, prior to randomization

• NOTES:

• Historical values of blood eosinophil count meeting the eligibility criterion measured within 6 months prior to screening Visit 1 in the absence of oral corticosteroid (OCS) treatment are allowed

• FeNO value to be checked for eligibility at Visit 2 as well

• Asthma control questionnaire (ACQ)-5 ≥2.5 at screening Visit 1 and Visit 2, prior to randomization

• Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) ≤ 80% of predicted normal during screening, prior to randomization

• Exhibit bronchodilator reversibility (≥12% and 200 mL improvement in FEV1 post short-acting beta agonist administration) during screening period, prior to randomization, unless reversibility test meeting the inclusion criteria was done within 6 months prior to screening Visit 1

• Weekly average nocturnal awakenings due to asthma symptoms in the week prior to screening Visit 1 is ≥1

Exclusion criteria:

• Current smoker

• Former smoker for 10 years with a smoking history of >10 pack-years

• Asthma exacerbation during screening, prior to randomization

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

• History of or current evidence of clinically significant non-respiratory diseases that in the opinion of the investigator may interfere with the aims of the study or put the participant at undue risk

• Active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded 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 would be performed on a country by country basis, according to local guidelines if required by Regulatory Authorities or ethics boards

• Diagnosed active endoparasitic infection; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization

• History of human immunodeficiency (HIV) infection or positive HIV test at screening Visit 1

• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before screening

• Known or suspected immunodeficiency including history of invasive opportunistic infections, despite infection resolution

• Current evidence of clinically significant oncological disease

• History of systemic hypersensitivity or anaphylaxis to any biologic therapy

• Severe uncontrolled depression

• Sleep disturbances not related to asthma, including sleep apnea, hypersomnia, or insomnia secondary to chronic pain, atopic dermatitis (AD), COPD or other conditions

• Participant who works night shift (ie, any work between 8 pm and 6 am)

• Erratic sleep habits, as determined by the Investigator

• Restless leg syndrome or periodic limb movement disorder

• Chronic treatment with oral corticosteroid (OCS) for more than 2 weeks before screening Visit 1

• Participant taking sedative, anxiolytic, or hypnotic treatments, including melatonin, within 3 months before randomization

• Participant taking systemic sedative antihistamines (excluding newer generations of antihistamines) or theophylline

• Current treatment with antidepressants, lipophilic beta blockers, clonidine, opioids, or other medications known to interfere with sleep and may confound the study assessments, as determined by the Investigator

• Participant who has taken biologic therapy (including dupilumab)/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc) within 2 months or 5 half-lives before screening Visit 1, whichever is longer

• Treatment with live (attenuated) vaccine within 4 weeks before screening Visit 1

• NOTE: For participants who have vaccination with live, attenuated vaccines planned during the course of the study (based on national vaccination schedule/local guidelines), it will be determined, after consultation with a physician, whether the administration of vaccine can be postponed until after the end of the study, (i.e. after the 12 week follow-up period off-treatment or until the participant switches to commercialized dupilumab or other biologic product, whichever comes first), or preponed to before the start of the study without compromising the health of the participant:

• Participant for whom administration of live (attenuated) vaccine can be safely postponed would be eligible to enroll into the study

• Participant who have their vaccination preponed can enroll in the study only after a gap of 4 weeks following administration of the vaccine

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	Investigational Site Number :8400003	Bakersfield	California	United States	93301
2	Investigational Site Number :8400009	Los Angeles	California	United States	90048
3	Investigational Site Number :8400001	San Jose	California	United States	95117
4	Investigational Site Number :8400011	Colorado Springs	Colorado	United States	80907
5	Investigational Site Number :8400012	Sarasota	Florida	United States	34239
6	Investigational Site Number :8400004	Owensboro	Kentucky	United States	42301
7	Investigational Site Number :8400010	Bellevue	Nebraska	United States	68123
8	Investigational Site Number :8400005	Edmond	Oklahoma	United States	73034
9	Investigational Site Number :8400007	Medford	Oregon	United States	97504
10	Investigational Site Number :8400008	Charleston	South Carolina	United States	29407
11	Investigational Site Number :8400006	Boerne	Texas	United States	78006
12	Investigational Site Number :0320003	Caba	Buenos Aires	Argentina	C1414AIF
13	Investigational Site Number :0320001	Caba	Buenos Aires	Argentina	C1425FVH
14	Investigational Site Number :0320004	Rosario	Santa Fe	Argentina	S2000DEJ
15	Investigational Site Number :0320005	Rosario	Santa Fe	Argentina	S2002OJP
16	Investigational Site Number :0320002	Buenos Aires		Argentina	C1121ABE
17	Investigational Site Number :1240012	Ajax	Ontario	Canada	L1S 2J5
18	Investigational Site Number :1240005	Toronto	Ontario	Canada	M9V 4B4
19	Investigational Site Number :1240009	Quebec		Canada	G1G 3Y8
20	Investigational Site Number :1240008	Windsor		Canada	N8X 5A6
21	Investigational Site Number :2760002	Berlin		Germany	10787
22	Investigational Site Number :2760005	Frankfurt am Main		Germany	60596
23	Investigational Site Number :2760003	Hannover		Germany	30173
24	Investigational Site Number :2760001	Koblenz		Germany	56068
25	Investigational Site Number :2760004	Leipzig		Germany	04347
26	Investigational Site Number :2760006	Lübeck		Germany	23552
27	Investigational Site Number :3800006	Monserrato	Cagliari	Italy	09042
28	Investigational Site Number :3800001	Orbassano	Torino	Italy	10043
29	Investigational Site Number :3800004	Catania		Italy	95123
30	Investigational Site Number :3800005	Reggio Emilia		Italy	42123
31	Investigational Site Number :5280005	Arnhem		Netherlands	6815 AD
32	Investigational Site Number :5280001	Breda		Netherlands	4818 CK
33	Investigational Site Number :5280002	Leeuwarden		Netherlands	8934 AD
34	Investigational Site Number :6200001	Aveiro		Portugal	3810-501
35	Investigational Site Number :6200008	Coimbra		Portugal	3000-075
36	Investigational Site Number :6200007	Guimarães		Portugal	4810-061
37	Investigational Site Number :6200006	Lisboa		Portugal	1769
38	Investigational Site Number :6200003	Matosinhos		Portugal	4464-513
39	Investigational Site Number :6200004	Porto		Portugal	4202-451
40	Investigational Site Number :6430001	Moscow		Russian Federation	115093
41	Investigational Site Number :6430002	Moscow		Russian Federation	115280
42	Investigational Site Number :6430006	Moscow		Russian Federation	115478
43	Investigational Site Number :6430005	Moscow		Russian Federation	117546
44	Investigational Site Number :6430007	St-Petersburg		Russian Federation	193231
45	Investigational Site Number :6430004	St-Petersburg		Russian Federation	194354
46	Investigational Site Number :7240003	Barcelona	Barcelona [Barcelona]	Spain	08036
47	Investigational Site Number :7240001	Lugo / Lugo	Galicia [Galicia]	Spain	27003
48	Investigational Site Number :7240006	Pozuelo De Alarcón	Madrid	Spain	28223
49	Investigational Site Number :7240002	Valencia	Valenciana, Comunidad	Spain	46017
50	Investigational Site Number :7240005	Madrid		Spain	28006
51	Investigational Site Number :8040002	Ivano-Frankivsk		Ukraine	76018
52	Investigational Site Number :8040006	Ivano-Frankivsk		Ukraine	76018
53	Investigational Site Number :8040003	Kharkiv		Ukraine	61166
54	Investigational Site Number :8040008	Kyiv		Ukraine	01023
55	Investigational Site Number :8040007	Kyiv		Ukraine	01033
56	Investigational Site Number :8040005	Vinnytsya		Ukraine	21001
57	Investigational Site Number :8260001	Cambridge	Cambridgeshire	United Kingdom	CB2 2QQ
58	Investigational Site Number :8260002	London	London, City Of	United Kingdom	EC1M 6BQ

Sponsors and Collaborators

• Sanofi
• Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT04502862
• Other Study ID Numbers: LPS16677; 2020-001217-20; U1111-1249-6054
• First Posted: Aug 6, 2020
• Last Update Posted: Jul 6, 2022
• Last Verified: Jul 4, 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
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Jul 6, 2022