NCT04502862: MORPHEO

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

Completed Phase 4 Results posted Last updated 6 December 2024

What this trial tests

Phase 4 trial testing SAR231893 in Asthma in 202 participants. Completed in 10 November 2023.

Timeline

10 August 2020

Primary endpoint
3 October 2023

10 November 2023

Quick facts

Lead sponsor	Sanofi
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	202
Start date	10 August 2020
Primary completion	3 October 2023
Estimated completion	10 November 2023
Sites	55 locations across Italy, Netherlands, Russia, Ukraine, United Kingdom, Germany, Argentina, Canada

Drugs / interventions tested

• SAR231893 — full drug profile →
• Placebo

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

Sanofi — full company profile →

Who can join

Adults 18 to 65, any sex, with Asthma. 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.

Change From Baseline to Week 12 in Sleep Disturbance Score Using the Asthma Sleep Disturbance Questionnaire (ASDQ) Primary · Baseline (Day -6 to Day 1) up to Week 12

The ASDQ is a participant-reported outcome (PRO) measure designed to assess the impact of asthma on participants' sleep. Participants were instructed to record the severity of the disturbance of their sleep due to asthma as: 0 = slept through the night, no asthma symptoms; 1 = slept well, no night time awakenings because of asthma, but some asthma symptoms in the morning; 2 = woke up once because of asthma (may or may not include early awakening); 3 = woke up several times because of asthma (may or may not include early awakening) and 4 = bad night, awake most of the night because of asthma. T

Group	Value	95% CI
Dupilumab 200 mg Q2W	-0.88	± 0.077
Placebo	-0.81	± 0.077

Change From Baseline to Week 12 on the Number of Nocturnal Awakenings (Sleep Diary) Secondary · Baseline (Day -6 to Day 1) up to Week 12

Sleep diary is used to assess adult sleep disturbance due to asthma. Number of nocturnal awakenings was determined based on answer on question from sleep diary: "Approximately how many times did you wake up last night (not including when you woke up for the day today)?" Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Group	Value	95% CI
Dupilumab 200 mg Q2W	-0.71	± 0.080
Placebo	-0.71	± 0.080

Change From Baseline to Week 12 in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment 8a Scale Secondary · Baseline (Day 1) up to Week 12

PROMIS sleep-related impairment eight-term 8a scale was administered to assess impact of sleep-related impairment during waking hours. The questionnaire focuses on self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours, and perceived functional impairments during wakefulness associated with sleep problems or impaired alertness. It assesses sleep-related impairment over the past 7 days. Each item is rated on a 5-point scale (1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; and 5 = very much) with a raw score from 8 to 40 with higher scores in

Group	Value	95% CI
Dupilumab 200 mg Q2W	-7.20	± 0.624
Placebo	-6.51	± 0.626

Change From Baseline to Week 12 in Sleep Quality (Sleep Diary) Secondary · Baseline (Day -6 to Day 1) up to Week 12

Sleep diary is used to assess adult sleep disturbance due to asthma. Sleep quality was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Group	Value	95% CI
Dupilumab 200 mg Q2W	1.14	± 0.151
Placebo	0.97	± 0.152

Change From Baseline to Week 12 in Restorative Sleep (Sleep Diary) Secondary · Baseline (Day -6 to Day 1) up to Week 12

Sleep Diary is used to assess adult sleep disturbance due to asthma. Question about restorative sleep asks participants to recall "when they got up for the day today". Restorative sleep was assessed on a 11-point scale which ranged from 0 (worst possible sleep) to 10 (best possible sleep); higher scores indicated better outcomes. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Group	Value	95% CI
Dupilumab 200 mg Q2W	1.15	± 0.152
Placebo	1.02	± 0.152

Change From Baseline to Week 12 in Wake After Sleep Onset (WASO) (Sleep Diary) Secondary · Baseline (Day -6 to Day 1) up to Week 12

Sleep Diary is used to assess adult sleep disturbance due to asthma. WASO was calculated as time awake after initial sleep onset but before the final awakening. Baseline was calculated by averaging the data collected/recorded from Day -6 to Day 1.

Group	Value	95% CI
Dupilumab 200 mg Q2W	-30.58	± 3.945
Placebo	-26.48	± 3.962

Change From Baseline to Week 12 in WASO Based on Actigraphy Data Secondary · Baseline (Day -6 to Day 1) up to Week 12

Wrist actigraphy is a procedure that records and integrates occurrence and degree of limb movement activity over an extended recording period. The signals generated by wrist movement are sensed by a tiny microcomputer contained within watch and translated into activity counts. Algorithms have been developed to translate these activity counts or "epochs" (or "periods") that correspond to times when a person is likely to be asleep or wake. Actigraph was worn on wrist of non-dominant hand to provide estimates of duration, timing and patterns of sleep in study participants. After the watch data we

Group	Value	95% CI
Dupilumab 200 mg Q2W	-1.64	± 2.286
Placebo	-1.17	± 2.215

Change From Baseline to Week 12 in Asthma Daytime Symptom Diary (ADSD) Secondary · Baseline (Day -7 to Day -1) up to Week 12

The ADSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ADSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now. ADSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = N

Group	Value	95% CI
Dupilumab 200 mg Q2W	-1.78	± 0.192
Placebo	-1.56	± 0.193

Change From Baseline to Week 12 in Asthma Nighttime Symptom Diary (ANSD) Secondary · Baseline (Day -6 to Day -1) up to Week 12

The ANSD is a PRO measure designed to measure asthma symptoms in adult and adolescent (12 years of age and older) participants diagnosed with mild to severe asthma. ANSD assesses asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty breathing, wheezing, shortness of breath, chest tightness, chest pain, and cough. Participants were asked to complete the ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. ANSD is composed of 6 items rated using an 11-point NRS that ranges from 0 = None to 10 = as bad as

Group	Value	95% CI
Dupilumab 200 mg Q2W	-1.58	± 0.178
Placebo	-1.36	± 0.178

Change From Baseline to Week 12 in Pre-Bronchodilator Forced Expiratory Volume (Pre-BD FEV1) Secondary · Baseline (Day 1) up to Week 12

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer. For pre-BD FEV1, spirometry was performed before IMP administration and after withholding the standard of care asthma treatment which was verified before performing the measurements. Baseline was defined as the last available valid (non-missing) value up to and including the day of first dose of IMP.

Group	Value	95% CI
Dupilumab 200 mg Q2W	0.49	± 0.044
Placebo	0.27	± 0.047

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-Emergent Adverse Events Of Special Interest (TEAESIs) Secondary · From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks

AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs: AEs that developed or worsened or became serious during TEAE period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 98 days or until participant switches to commercialized dupilumab or other biologics. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongati

Any TEAE

Group	Value	95% CI
Dupilumab 200 mg Q2W	48
Placebo	46

Any TESAE

Group	Value	95% CI
Dupilumab 200 mg Q2W	3
Placebo	3

Any TEAESI

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	0

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs Secondary · From first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks

Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and weight. Criteria for PCSA: SBP: ≤95 millimeters of mercury (mmHg) and decrease from baseline ≥20 mmHg, ≥160 mmHg and increase from baseline ≥20 mmHg; DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; HR: ≤ 50 beats per minute (bpm) and decrease from baseline ≥ 20 bpm, ≥120 bpm and increase from baseline ≥ 20 bpm; Weight: ≥ 5% increase from baseline, ≥5% decrease from baseline.

SBP: ≤95 mmHg and decrease from baseline ≥20 mmHg

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	1

SBP: ≥160 mmHg and increase from baseline ≥20 mmHg

Group	Value	95% CI
Dupilumab 200 mg Q2W	1
Placebo	2

DBP: ≤45 mmHg and decrease from baseline ≥10 mmHg

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	0

DBP: ≥ 110 mmHg and increase from baseline ≥ 10mmHg

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	0

HR: ≤ 50 bpm and decrease from baseline ≥ 20 bpm

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	0

HR: ≥ 120 bpm and increase from baseline ≥ 20 bpm

Group	Value	95% CI
Dupilumab 200 mg Q2W	0
Placebo	0

Weight: ≥5% increase from baseline

Group	Value	95% CI
Dupilumab 200 mg Q2W	3
Placebo	6

Weight: ≥5% decrease from baseline

Group	Value	95% CI
Dupilumab 200 mg Q2W	5
Placebo	4

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAEs were collected from first dose of study drug (Day 1) up to 12 weeks after last dose of study drug, approximately 30 weeks. All-cause mortality (deaths) were collected from first dose of study drug (Day 1) up to end of study, approximately 39 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dupilumab 200 mg Q2W

Serious: 3/100 (3%)

Deaths: 0/100

Placebo

Serious: 3/101 (3%)

Deaths: 0/101

Serious adverse events (9 terms)

Reaction	System	Dupilumab 200 mg Q2W	Placebo
Pancreatitis Acute	Gastrointestinal disorders	—	—
Covid-19 Pneumonia	Infections and infestations	—	—
Urosepsis	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Tibia Fracture	Injury, poisoning and procedural complications	—	—
Depression Suicidal	Psychiatric disorders	—	—
Suicide Attempt	Psychiatric disorders	—	—
Nephrolithiasis	Renal and urinary disorders	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Dupilumab 200 mg Q2W	Placebo
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—

Most-reported serious reactions: Pancreatitis Acute, Covid-19 Pneumonia, Urosepsis, Fall, Tibia Fracture, Depression Suicidal, Suicide Attempt, Nephrolithiasis.

Data from ClinicalTrials.gov NCT04502862 adverse events section.

Sponsor's own description

Primary Objective:

To assess the effect of dupilumab on sleep

Secondary Objectives:

* To evaluate the effect of dupilumab on additional participant 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

Publications & conference data

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

1. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons.
   Hussain M, Liu G. · · 2024 · cited 60× · PMID 38474348 · DOI 10.3390/cells13050384
2. Dupilumab and tezepelumab in severe refractory asthma: new opportunities.
   Ragnoli B, Morjaria J, Pignatti P, Montuschi P, et al · · 2022 · cited 7× · PMID 35655942 · DOI 10.1177/20406223221097327
3. Content Validation of Patient-Reported Sleep Measures and Development of a Conceptual Model of Sleep Disturbance in Patients with Moderate-to-Severe, Uncontrolled Asthma.
   Khan AH, Kosa K, De Prado Gomez L, Whalley D, et al · · 2023 · cited 3× · PMID 36992797 · DOI 10.2147/prom.s392666