Asthma ControlPhase 3HOTHOTNCT07309614
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
A Phase 3 study testing Dupilumab Prefilled Syringe in people with Asthma Control, run by Université de Sherbrooke at 5 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Asthma Control
- What is being tested?
- Dupilumab Prefilled Syringe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 29 Jan 2026to Jan 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 informed consent.
- 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:
- Positive reversibility test: ≥12% and 200 ml in FEV1 after SABA administration at any point prior to randomisation
Show all 44Show fewer
- Airflow variability in clinic FEV1 >12% and 200 mL between historical clinical visits
- Positive bronchial challenge test: fall in FEV1 of ≥20% with standard doses of methacholine (<16 mg/mL or <400mcg); or ≥10% with standardised hyperventilation, or exercise challenge test; or ≥15% with hypertonic saline or mannitol challenge
- Peak flow variability of >20% between two assessments
- Evidence of elevated type-2 biomarkers defined as both of:
- peripheral BEC ≥ 0.3×109/L at screening visit
- FeNO ≥ 35 ppb at screening visit
- At least 1 asthma attack in the last 2 years, defined as acute asthma requiring SCS for ≥ 3 days or an emergency/hospital visit requiring SCS.
- 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, contraceptive/barrier method and pregnancy testing requirements
- Female participants
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is a woman of nonchildbearing potential (WONCBP) as defined in the Study Manual.
- OR ii. Is a WOCBP 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.
- 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.
- Additional requirements for pregnancy testing during and after study intervention are imposed.
- 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
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- 4.2 EXCLUSION CRITERIA
- Participants are excluded from the study if any of the following criteria apply:
- Medical conditions
- Use of SCS < 1 months prior to screening or on maintenance SCS.
- Current tobacco smoker or recently stopped smoker (<6 months)
- Ex-smoker with greater than 10 pack-years AND post bronchodilator FEV1/FVC ratio below the lower limit of normal according to GLI race-neutral standards. 69
- Documented nonadherence to ICS, defined as dispensing of less than 75% of the prescribed ICS dose over the past 12 months (or annualised if less than 12 months), based on pharmacy refill records checked at screening.
- Presence of significant and uncorrectable inhaler technique deficiencies, as assessed by the research team during inhaler technique evaluation at screening.
- Contra-indication to study drug
- Immunological disease, condition or medication that may affect the inflammatory response according to Investigator.
- History of other significant lung disease e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, clinically significant bronchiectasis, chronic obstructive lung disease, or Churg-Strauss.
- Severe concomitant illness (including known or suspected immunodeficiency) that, in the Investigator's judgement will adversely affect the participant's participation in the study.
- Active malignancy or history of malignancy within 5 years (except for basal cell carcinoma of the skin or fully resected Cervical Intraepithelial Neoplasia/dysplasia).
- Exposure to monoclonal antibody therapy for asthma or another investigational medicinal product within 5 half-lives of the drug.
- Eligibility to Dupilumab based on licensed and reimbursed indications in the participant's jurisdiction (e.g. nasal polyposis, atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, etc.)
- Treatment with live (attenuated) vaccine in the past 4 weeks.
- Prohibited medication
- Current helminth infection
Who cannot join
None listed.
Trial locations and contacts
5 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 3 countries
Canada3 sites, 3 recruiting
- Not yet recruiting
McGill University Health Centre
Montreal, Quebec, H4A 3S5
Cathy Fugere, (514) 934-1934, cathy.fugere@affiliate.mcgill.ca
Narmin Diab, MD
- Recruiting
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, G1V 4G5
Claudine Ferland, (418) 656-8711, claudine.ferland@criucpq.ulaval.ca
Andréanne Côté, MD
- Recruiting
CIUSSS de l'Estrie- CHUS
Sherbrooke, Quebec, J1H 5H6
Amélie Tétu, 819-346-1110, amelie.tetu.ciussse-chus@ssss.gouv.qc.ca
Simon Couillard, MD
Australia1 site, 1 recruiting
- Recruiting
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Meagan Shorten, 61 8 6488 6000, "meagan.shorten@resphealth.uwa.edu.au
Sanjay Ramakrishnan, MD
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Oxford University Hospitals NHS Foundation Trust - John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Melissa Dobson, +44 300 304 7777, "melissa.dobson@ndm.ox.ac.uk" <melissa.dobson@ndm.ox.ac.uk>
Nayia Petousi, MD
About this study
Official title: A Multinational, Investigator-initiated, Parallel Group, Randomised, Double-blind, Placebo-controlled Phase 3b Superiority Trial Assessing the Effect of Dupilumab on Inducing Clinical Remission Outcomes in At-risk Type-2 Inflammatory Asthma (HOTHOT)
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
Read the detailed description
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.
- Conditions
- Asthma Control
- Being tested
- Dupilumab Prefilled Syringe, Placebo Injection
- Keywords
- Asthma, Asthma control, moderate asthma, dupilumab, remission, type-2 inflammation, blood eosinophils, feno, exacerbations, trial, RCT
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dupilumab Prefilled SyringeDrug
Dupilumab 400mg subcut x1 followed by 200mg subcut every 2 weeks
Placebo InjectionDrug
Volume-matched placebo injected subcut every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo Injection |
| Dupilumab | Experimental | Not described Receives: Drug: Dupilumab Prefilled Syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Study participant has not had a severe asthma attack between weeks 4 and 56
- Number of asthma attacks between weeks 4 and 56
- 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
- No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56
- 5-item Asthma Control Questionnaire mean score <1.5 at Week 56
Measured: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
Secondary outcomes (18)
Annualised severe asthma attack rate
Reduction in annualised severe asthma attack rate with dupilumab vs placebo
Measured: 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:
- Study participant has not had a severe asthma attack between weeks 4 and 56
- Number of asthma attacks between weeks 4 and 56
- 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
- No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56
- 5-item Asthma Control Questionnaire mean score <1.5 at Week 56
Measured: 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
Measured: 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:
- Study participant has not had a severe asthma attack between weeks 4 and 56
- 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
- No more than medium-dose ICS maintenance therapy (as defined by GINA 2025) at Week 56
- ACQ5 <1.5 at Week 56
Measured: 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)
Measured: 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.
Measured: Week 0 to Week 56
Effect of dupilumab on absenteism, compared to placebo
Cumulative time off work or education due to asthma symptoms
Measured: Week 0 to Week 56
Effect of dupilumab on unplanned healthcare attendencances, compared to placebo
Cumulative number of unplanned healthcare attendances
Measured: Week 0 to Week 56
Effect of dupilumab on emergency room attendance, compared to placebo
Cumulative number of emergency department visits
Measured: Week 0 to Week 56
Effect of dupilumab on hospilisation use, compared to placebo
Cumulative number of hospitalisations
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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.
Measured: Week 0 to Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2025
- Study start29 Jan 2026
- Primary completionJan 2029 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Asthma ControlStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double blinded study assessing intervention versus placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, University of Oxford, The University of Western Australia, Regeneron Pharmaceuticals, Fonds de la Recherche en Santé du Québec, Association Pulmonaire du Quebec
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07309614
- Sponsor's protocol ID
- 2024ESR0000238
- Acronym
- HOTHOT
- Status last verified
- Sep 2026
- First submitted
- 25 Nov 2025
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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
Publications
Couillard S, Petousi N, Ramakrishnan S, Valle R, Tetu A, Lemaire-Paquette S, Xia C, Poirier S, Ledanois O, Gall R, Cote A, Diab N, Lachapelle P, Pavord ID. Protocol for a multinational, investigator-initiated, parallel-group, randomized, double-blind, placebo-controlled phase 3b superiority trial assessing the effect of dupilumab on inducing clinical remission outcomes in at-risk type-2 inflammatory asthma (HOTHOT). Ann Allergy Asthma Immunol. 2026 Jul;137(1):116-123.e26. doi: 10.1016/j.anai.2026.03.028. Epub 2026 Apr 11.
PubMed 41967704
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multinational, Investigator-initiated, Parallel Group, Randomised, Double-blind, Placebo-controlled Phase 3b Superiority Trial Assessing the Effect of Dupilumab on Inducing Clinical Remission Outcomes in At-risk Type-2 Inflammatory Asthma (HOTHOT)
- ClinicalTrials.gov ID
- NCT07309614
- Acronym / sponsor ID
- HOTHOT / 2024ESR0000238
- Conditions
- Asthma Control
- Keywords
- Asthma, Asthma control, moderate asthma, dupilumab, remission, type-2 inflammation, blood eosinophils, feno
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- Sanofi, University of Oxford, The University of Western Australia, Regeneron Pharmaceuticals, Fonds de la Recherche en Santé du Québec, Association Pulmonaire du Quebec
- Study start
- 29 Jan 2026 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 30 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double blinded study assessing intervention versus placebo
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo Injection |
| Dupilumab | Experimental | Drug: Dupilumab Prefilled Syringe |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- 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 informed consent.
- 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:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dupilumab Prefilled SyringeDupilumab 400mg subcut x1 followed by 200mg subcut every 2 weeks | Drug | Dupilumab |
| Placebo InjectionVolume-matched placebo injected subcut every 2 weeks | Drug | Placebo |
Primary outcome
Win ratio based on remission criteria
Time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
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
18 secondary outcomes
Annualised severe asthma attack rate
Time frame: Week 4 to Week 56
Win ratio for clinical remission in medium-dose ICS subgroup
Time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)
Change in FEV1 postbronchodilator
Time frame: Week 0 to Week 56
Proportion of patients achieving clinical remission at 1 year
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
Time frame: Week 0 to Week 56
Effect of dupilumab on asthma symptoms, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on absenteism, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on unplanned healthcare attendencances, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on emergency room attendance, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on hospilisation use, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on asthma-related quality of life, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on respiratory disease-related quality of life, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on health-related quality of life, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on work and activity productivity, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on maintenance ICS dose, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on type-2 biomarkers, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab on reported usage of reliever medication, compared to placebo
Time frame: Week 0 to Week 56
Effect of dupilumab vs placebo on sino-nasal symptoms
Time frame: Week 0 to Week 56
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Derived from this study: PubMed 41967704Couillard S, Petousi N, Ramakrishnan S, Valle R, Tetu A, Lemaire-Paquette S, Xia C, Poirier S, Ledanois O, Gall R, Cote A, Diab N, Lachapelle P, Pavord ID. Protocol for a multinational, investigator-initiated, parallel-group, randomized, double-blind, placebo-controlled phase 3b superiority trial assessing the effect of dupilumab on inducing clinical remission outcomes in at-risk type-2 inflammatory asthma (HOTHOT). Ann Allergy Asthma Immunol. 2026 Jul;137(1):116-123.e26. doi: 10.1016/j.anai.2026.03.028. Epub 2026 Apr 11.
- Individual participant dataSharing planned: 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
Related trials for Asthma Control
Recruiting
Acoustic Waveform Respiratory Evaluation
Asthma, COPD
Recruiting
Boosting Referrals to Asthma Specialists for Patients Seen at the Emergency Room for an Asthma Exacerbation
Asthma Attack, Asthma Control
Not yet recruitingObservational study
NLR, ELR and SII Index as Biomarkers of Asthma Control
Asthma Control
Recruiting
The Development of the Walsh Asthma Self-management Programme and Feasibility of Implementation in Adults With Asthma in Primary Care
Asthma, Self-management
Not yet recruiting
Replacing Gas Stoves With Portable Electric Appliances to Improve Indoor Air Quality and Asthma Control
Asthma Control
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Canada
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dupilumab Prefilled Syringe in people with Asthma Control, run by Université de Sherbrooke at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Win ratio based on remission criteria (time frame: Week 4 to Week 56 (except FEV1 change: Week 0 values serve as baseline)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07309614, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026; AzTrials last refreshed its copy on 7 Nov 2026.