Trial Outcomes & Findings for Add-on Dupilumab for AFRS as Postoperative Therapy (ADAPT) (NCT NCT05545072)

Results Overview

The efficacy of dupilumab in controlling sinonasal inflammation and preventing nasal polyp recurrence after complete sinus surgery for allergic fungal rhinosinusitis (AFRS) is assessed by using the modified Lund-Kennedy score. The modified Lund-Kennedy score (mLK) is a validated measure of sinonasal inflammation, as evaluated by means of nasal endoscopy. The composite score ranges from 0 to 12, with an increasing score representing worsening inflammation among three separate findings (Nasal polyps, Discharge, Edema). Each finding is rated from 0 (absent) to 2 (severe). A ≥ 2-point increase from baseline total postoperative score represents a clinically significant worsening of sinonasal inflammation.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

5 participants

Primary outcome timeframe

Baseline and End of Treatment at Week 52

Results posted on

2025-05-08

Participant Flow

Participants were planned for recruitment from three locations in the USA: the University of Texas Health Science Center at Houston, in Houston, Texas, and Emory University Hospital Midtown and Emory University Hospital in Atlanta, Georgia. Participant enrollment began October 26, 2023, and the final study visit occurred July 10, 2024. The University of Texas Health Science Center at Houston was not activated as a site, and all participants were recruited at the Emory site.

Participant milestones

Participant milestones
Measure	Dupilumab Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Overall Study STARTED	3	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Dupilumab Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Overall Study Lost to Follow-up	1	0
Overall Study Study ended prematurely due to funding	2	2

Baseline Characteristics

Add-on Dupilumab for AFRS as Postoperative Therapy (ADAPT)

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Data are not available for the calculation of the mLK score as the study was terminated before central reader scoring of the nasal endoscopy.

The efficacy of dupilumab in controlling sinonasal inflammation and preventing nasal polyp recurrence after complete sinus surgery for allergic fungal rhinosinusitis (AFRS) is assessed by using the modified Lund-Kennedy score. The modified Lund-Kennedy score (mLK) is a validated measure of sinonasal inflammation, as evaluated by means of nasal endoscopy. The composite score ranges from 0 to 12, with an increasing score representing worsening inflammation among three separate findings (Nasal polyps, Discharge, Edema). Each finding is rated from 0 (absent) to 2 (severe). A ≥ 2-point increase from baseline total postoperative score represents a clinically significant worsening of sinonasal inflammation.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

The number of participants who, during study treatment and off-treatment follow-up, based on clinical evaluation, present worsening signs and/or symptoms and are started on oral corticosteroids rescue treatment.

Outcome measures

Outcome measures
Measure	Dupilumab n=3 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=2 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Incidence of Oral/Topical Corticosteroid Utilization Per Participant Baseline	3 Participants	2 Participants
Incidence of Oral/Topical Corticosteroid Utilization Per Participant Week 12	0 Participants	0 Participants
Incidence of Oral/Topical Corticosteroid Utilization Per Participant Week 24	0 Participants	—

SECONDARY outcome

Timeframe: Up to End of Treatment at Week 52

Documentation of the number of revision sinus surgery per participant, that are deemed clinically necessary for the treatment of an acute exacerbation of chronic rhinosinusitis (AECRS)

Outcome measures

Outcome measures
Measure	Dupilumab n=3 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=2 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Prevalence of Revision Sinus Surgery for Recurrent Nasal Polyps, and Comparison of Survival Curves	0 Revision Surgeries per participant Standard Deviation 0	0 Revision Surgeries per participant Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

NPS is a physician-reported tool to grade the extent/severity of nasal polyps based on evaluation by nasal endoscopy. Each nostril is scored on a scale of 0 (no polyps visible) to 4 (massive polyposis completely obstructing the nasal cavity), with the total score being the sum of left and right nostril scores (range: 0-8). The total NPS is the sum of scores from the right and left nostrils.

Outcome measures

Outcome measures
Measure	Dupilumab n=3 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=2 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Endoscopic Nasal Polyp Score (NPS) Baseline	4.33 Score on a scale Standard Deviation 0.47	5 Score on a scale Standard Deviation 1
Endoscopic Nasal Polyp Score (NPS) Week 12	1 Score on a scale Standard Deviation 0	0 Score on a scale Standard Deviation 0
Endoscopic Nasal Polyp Score (NPS) Week 24	2 Score on a scale Standard Deviation 0	—

SECONDARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

Spirometry is a common office test used to assess how well the participant's lungs work by measuring how much air the participant inhales, how much the participant exhales, and how quickly the participant exhales. Forced vital capacity (FVC) refers to the maximal volume of air that can be expired following maximum inspiration. It is the total of tidal volume, inspiratory reserve volume, and expiratory reserve volume. The percent FVC is the FVC compared to a predicted FVC based on age, sex, and height.

Outcome measures

Outcome measures
Measure	Dupilumab n=2 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=1 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Percent Predicted Forced Vital Capacity (%FVC) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%) Baseline	107 %FVC Standard Deviation 3	104 %FVC Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

Forced expiratory volume in one second (FEV1) is measured during a spirometry test, also known as a pulmonary function test, which involves forcefully breathing out into a mouthpiece connected to a spirometer machine. FEV1 is the amount of air forced from the lungs in one second.

Outcome measures

Outcome measures
Measure	Dupilumab n=2 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=1 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Forced Expiratory Volume in 1 Second (FEV1) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%) Baseline	3.55 Liter Standard Deviation 0.76	2.80 Liter Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

Forced vital capacity (FVC) is measured during a spirometry test, also known as a pulmonary function test, which involves forcefully breathing out into a mouthpiece connected to a spirometer machine. FVC is the total amount of air exhaled during the FEV test.

Outcome measures

Outcome measures
Measure	Dupilumab n=3 Participants Participants receiving dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Dupilumab: Dupilumab will be administered subcutaneously at a dose of 300 milligrams (mg) in a 2 milliliter (mL) solution every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.	Placebo n=2 Participants Participants receiving a placebo to match dupilumab for 52 weeks following surgery for allergic fungal rhinosinusitis (AFRS). Placebo: A placebo to match dupilumab will be administered subcutaneously every 2 weeks until the end of treatment (EOT) at Week 52. Participants will receive a total of 26 doses. Intranasal Corticosteroid Sprays (INCS): All participants will undergo standardized background therapy with intranasal corticosteroid sprays (INCS) per standard of care (SoC). This will be continued throughout the entire study. Participants either receive fluticasone propionate or mometasone furoate.
Forced Vital Capacity (FVC) Following Sinus Surgery in the Subgroup of Participants With Asthma (~25%) Baseline	4.67 liter Standard Deviation 1.07	3.53 liter Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline and End of Treatment at Week 52

Population: Participants were unable to complete the study visits as scheduled at 52 weeks due to the premature termination of the study. Data is reported up to the time point completed by all participants.

The FEV1/FVC ratio is the ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs. The normal value for this ratio is above 0.75-85, though this is age-dependent, values less than 0.70 are suggestive of airflow limitation with an obstructive pattern.