A Phase 3 interventional study of Dupilumab Prefilled Syringe and Placebo Injection in Asthma Control, sponsored by Université de Sherbrooke. Recruiting at 5 sites in 3 countries. Open to participants aged 18 Years to 79 Years. Per ClinicalTrials.gov, last updated 2026-11-06.
Sponsored by Université de Sherbrooke · Phase 3, Interventional, and Treatment
This study tests whether an asthma medication called dupilumab can help people achieve complete asthma control (called "remission") when given earlier in their disease, before asthma becomes severe. Currently, most people with asthma only receive advanced treatments like biologics after their condition has worsened significantly and caused lung damage. This study explores whether treating high-risk patients earlier could prevent asthma attacks and lung function decline, potentially achieving remission before permanent damage occurs. The study is looking for adults aged 18-79 with moderate asthma who have had at least one asthma attack requiring steroid pills in the past 2 years, use medium or high-dose inhaled steroids regularly, have high levels of inflammation markers in their blood and breath tests, but don't yet meet criteria for severe asthma requiring biologic therapy. Participants receive either dupilumab or placebo injections every 2 weeks for one year, alongside their regular asthma medications. They attend clinic visits every 3 months for breathing tests, questionnaires, and safety monitoring. Neither participants nor doctors know who receives the real medication until the study ends. The goal is to learn whether early treatment with dupilumab helps more people achieve complete asthma control compared to standard care alone, potentially changing how asthma is treated from "waiting until severe" to "preventing severe disease." The study runs in Canada, the United Kingdom, and Australia, involving 150 participants
Asthma is a prevalent chronic respiratory disease for which 44% of people require oral corticosteroids (OCS) every year 1 . Whilst asthma is still managed on a damage-based schema allowing for unacceptable toxicities and irreversible airway remodelling, dupilumab and other type-2 targeting biologics have taught us that people with the highest type-2 inflammatory burden can achieve life-changing responses 2-6 . The term 'remission' has been used to describe the best possible outcome with biologics 5 . Across studies and molecules, remission was more likely to be achieved in people with shorter disease duration, lower morbidity, and higher type-2 inflammatory biomarkers 5,7-9 . These observations have increased interest in the earlier use of biologics in a Predict and Prevent framework 5,10-12 .
The HOTHOT study is a double-blind, placebo-controlled study assessing the effect of dupilumab on induction of clinical remission outcomes in type-2 high patients recruited before they develop severe uncontrolled asthma meeting current biological treatment recommendations. Dupilumab will be compared with placebo in 150 patients undergoing traditional symptom-based inhaled corticosteroid (ICS) up- and down-titration (as per current asthma guidelines). The target population is at-risk type-2 high asthma, defined as at-least medium-dose ICS, with a previous history of a systemic corticosteroid (SCS)-treated asthma attack in the last 24 months and blood eosinophils ≥ 0.3×109/L plus exhaled nitric oxide ≥35 ppb. These inclusion criteria are unique because they will target people with asthma who are at risk of severe asthma attacks and lung function decline, also not meeting current biological prescription/reimbursement criteria. The one-year active treatment adjustment period of the study will test the hypothesis that remission outcomes are more likely to be achieved with early targeted intervention with dupilumab compared to traditional symptom-guided management, where ICS up- and down-titration occurs independently of the presence of type-2 inflammation. The primary outcome, the win ratio based on remission criteria, assesses the likelihood of achieving remission 'wins' based on a hierarchy of criteria, while the secondary remission multi-component (yes/no) outcome, a binary (yes/no) multi-component endpoint for remission, offers a straightforward and comprehensive measure. The primary and secondary remission outcome measurements are both powered to be statistically and clinically impactful to move the need forward in the field of asthma. If correct, the hypothesis that earlier intervention with dupilumab significantly induces remission will shift the treatment paradigm from the usual 'wait and react' approach to a proactive risk-based 'predict and prevent' intervention using earlier targeted therapy in at-risk type-2 inflammatory disease.
4,841 studies on the registry are indexed under Asthma; 600 are open to participants now.
This study's planned enrollment of 150 is above the median of 78 across 3,341 interventional studies indexed under Asthma.
Browse Asthma studies →Université de Sherbrooke is the lead sponsor of 295 studies on the registry; 65 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Oct 2, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Study participants are eligible to be included in the study only if all of the following criteria apply:
Age
Participant must be 18-\<80 years of age at the time of signing the .
Type of participant and disease characteristics
Physician diagnosis of asthma (according to GINA 2025) for ≥6 months, with documented historical airflow variability by one of the following:
Evidence of elevated type-2 biomarkers defined as both of:
Treatment and evident adherence to a stable at-least medium-dose ICS (fluticasone propionate equivalent >250 mcg/day) for at least 3 months (including run-in period) [additional controllers e.g. LABA, LAMA or LTA are allowed]. The ICS dosage will be defined as the dosage received on a regularly basis, excluding extra reliever doses taken in the context of anti-inflammatory reliever (AIR) therapy from the calculation. AIR is allowed in the context of the study. Thus, the high-dose ICS trial population (fluticasone propionate equivalent >500 mcg/day)* will represent patients who are not meeting the exacerbation criteria for biological reimbursement.
*As per section 6.2, we will cap recruitment to 60% of target population on medium-dose ICS, 40% on high-dose ICS, with randomisation also stratified by these categories.
Presence of one (or more) of the following additional risk factors for asthma attacks32 at screening or baseline: (i) uncontrolled asthma symptoms indicated by ACQ5 score of ≥ 1.5; (ii) impaired lung function indicated by post-bronchodilator FEV1 of ≤ 80% predicted; (iii) high-dose maintenance ICS therapy (iv) severe asthma attack in past 1-\<12 months.
Sex, /barrier method and pregnancy testing requirements
Female participants
a. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
i. Is a woman of nonchildbearing potential (WONCBP) as defined in the Study Manual.
OR ii. Is a and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1%, during the intervention period (to be effective before starting the intervention) and for at least 12 weeks after the last dose of study intervention.
b. A WOCBP must have a negative highly sensitive serum pregnancy test at V1 (screening visit) and urine or serum pregnancy test (as required by local regulations) on Day 1 before the first dose of study intervention, c. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
d. Additional requirements for pregnancy testing during and after study intervention are imposed.
e. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a female participant with an early undetected pregnancy.
Informed consent
4.2 EXCLUSION CRITERIA
Participants are excluded from the study if any of the following criteria apply:
Medical conditions
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Placebo Injection
Drug: Dupilumab Prefilled Syringe
Dupilumab 400mg subcut x1 followed by 200mg subcut every 2 weeks
Volume-matched placebo injected subcut every 2 weeks
This study also gives Dupilumab. No intervention listed here names it: that was found by reading the record.
Win ratio based on remission criteria
Win ratio comparing patients achieving clinical remission outcomes in dupilumab group vs placebo group, based on remission criteria. The unmatched paired testing will follow this hierarchy: 1. Study participant has not had a severe asthma attack between weeks 4 and 56 2. Number of asthma attacks between weeks 4 and 56 3. Improved or stable lung function (defined as a decline from parent study baseline in pre- or postbronchodilator FEV1 by no more than 5%) at Week 56 4. No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56 5. 5-item Asthma Control Questionnaire mean score \<1.5 at Week 56
Time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
Annualised severe asthma attack rate
Reduction in annualised severe asthma attack rate with dupilumab vs placebo
Time frame: Week 4 to Week 56
Win ratio for clinical remission in medium-dose ICS subgroup
Win ratio comparing remission outcomes in dupilumab vs placebo among patients on medium-dose ICS at enrolment. The unmatched paired testing will follow this hierarchy: 1. Study participant has not had a severe asthma attack between weeks 4 and 56 2. Number of asthma attacks between weeks 4 and 56 3. Improved or stable lung function (defined as a decline from parent study baseline in pre- or postbronchodilator FEV1 by no more than 5%) at Week 56 4. No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56 5. 5-item Asthma Control Questionnaire mean score \<1.5 at Week 56
Time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
Change in FEV1 postbronchodilator
Change in FEV1 postbronchodilator (L) with dupilumab vs placebo
Time frame: Week 0 to Week 56
Proportion of patients achieving clinical remission at 1 year
Proportion of patients achieving clinical remission at 1 year in dupilumab vs placebo group Study participants meet ALL of the follow criteria at Week 56: 1. Study participant has not had a severe asthma attack between weeks 4 and 56 2. Improved or stable lung function (defined as a decline from parent study baseline in pre- or postbronchodilator FEV1 by no more than 5%) at Week 56 3. No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56 4. ACQ5 \<1.5 at Week 56
Time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
Effect of dupilumab on corticosteroid use, compared to placebo
Cumulative prescribed dose of systemic corticosteroids (prednisone-equivalent mg)
Time frame: Week 0 to Week 56
Effect of dupilumab on asthma symptoms, compared to placebo
Change from in 5-item Asthma Control Questionnaire (mean score). The score ranges from 0 to 6 : higher scores indicate worse asthma control.
Time frame: Week 0 to Week 56
Effect of dupilumab on absenteism, compared to placebo
Cumulative time off work or education due to asthma symptoms
Time frame: Week 0 to Week 56
Effect of dupilumab on unplanned healthcare attendencances, compared to placebo
Cumulative number of unplanned healthcare attendances
Time frame: Week 0 to Week 56
Effect of dupilumab on emergency room attendance, compared to placebo
Cumulative number of emergency department visits
Time frame: Week 0 to Week 56
Effect of dupilumab on hospilisation use, compared to placebo
Cumulative number of hospitalisations
Time frame: Week 0 to Week 56
Effect of dupilumab on asthma-related quality of life, compared to placebo
Change in Asthma Quality of Life Questionnaire with Standardised Activities AQLQ(S). The score ranges from 1 to 7 : higher scores indicate better quality of life.
Time frame: Week 0 to Week 56
Effect of dupilumab on respiratory disease-related quality of life, compared to placebo
Change in Saint-George Respiratory Questionnaire. The score ranges from 0 to 100 : higher scores indicate worse health status.
Time frame: Week 0 to Week 56
Effect of dupilumab on health-related quality of life, compared to placebo
Change in health-related quality of life questionnaire EQ-5D. The index value typically ranges from approximately -0.59 to 1.0: higher values indicate better health related quality of life.
Time frame: Week 0 to Week 56
Effect of dupilumab on work and activity productivity, compared to placebo
Change in Work Productivity and Activity Impairment Score for asthma (WPAI-Asthma). The score ranges from 0 to 100 percent: higher values indicate greater impairment or worse outcomes.
Time frame: Week 0 to Week 56
Effect of dupilumab on maintenance ICS dose, compared to placebo
Change in maintenance ICS dose (continuous and categorical: very low, low, medium, high-dose , as per GINA 2025)
Time frame: Week 0 to Week 56
Effect of dupilumab on type-2 biomarkers, compared to placebo
Change in blood eosinophil count, FeNO, and IgE levels, expressed as % relative to baseline
Time frame: Week 0 to Week 56
Effect of dupilumab on reported usage of reliever medication, compared to placebo
Change in reported usage of reliever medication (mean reliever use per week)
Time frame: Week 0 to Week 56
Effect of dupilumab vs placebo on sino-nasal symptoms
Change in Sino Nasal Outcome Test 22 score. The score ranges from 0 to 110 : higher scores indicate worse symptom severity.
Time frame: Week 0 to Week 56
To describe exacerbation phenotypes and SCS-responsiveness in the dupilumab and placebo arms.
Change in FEV1 post-BD (L) following SCS treatment
Time frame: Pre- (day 1 of exacerbation, pre-treatment) and Post-treatment visit (day 7)
To evaluate safety of dupilumab in this population of patients
Incidence of treatment-emergent adverse events (TEAE) and serious adverse events (SAE) in treatment group vs placebo
Time frame: Week 0 to Week 56
Plan to share: Yes — At the time of publication of the study results, the REDCap data dictionary, analytical code used to process the data, and analytical code used to analyze the outcomes will be posted on Github. In addition, after the end of the study, the data collected as part of the study can be shared as follows: A copy of the coded data collected as part of the study and under the control of the sponsor will be created and all data will be : Anonymized and the sponsor will ensure to the fullest extent possible that the data irremediably no longer allows any study participant to be identified directly or indirectly; or Subject to additional de-identification process to remove additional identifiers to ensure that the data no longer allows the study participants to be directly identified; Following that process, the anonymized/further deidentified dataset could be shared with the participating sites and their respective investigators for their own internal and non-commercial uses in accordanc
Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code
Started Jan 2026 (actual). Primary completion is estimated for Jan 2029, 36 months after the start.
Of 32 non-industry phase 3 interventional studies under Asthma, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 54. This study's planned 36 months is close to that.
Counting every sponsor, half of 205 studies reached it within 27 months; a quarter within 14 and three quarters within 42.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drug tested here: Dupilumab