| CTRI Number |
CTRI/2022/05/042593 [Registered on: 17/05/2022] Trial Registered Prospectively |
| Last Modified On: |
13/06/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
Study assessing the efficacy and safety of dupilumab in patients with Allergic Fungal Rhinosinusitis (AFRS) |
|
Scientific Title of Study
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A randomized double-blind placebo-controlled parallel group study assessing the efficacy and safety of dupilumab in patients with Allergic Fungal Rhinosinusitis (AFRS) |
| Trial Acronym |
LIBERTY-AFRS-AIMS
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Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2020-002999-12 |
EudraCT |
| EFC16724 |
Protocol Number |
| U1111-1246-7549 |
Other |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Godhuli Chatterjee |
| Designation |
Senior Medical Advisor |
| Affiliation |
Sanofi Healthcare India Private Limited |
| Address |
Sanofi House, CTS No.117-B, L& T Business Park, Saki Vihar Road, Powai , Mumbai , Maharashtra, 400072.
Mumbai
MAHARASHTRA
400072
India |
| Phone |
919930151289 |
| Fax |
|
| Email |
Godhuli.Chatterjee@sanofi.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Vijay Mandal |
| Designation |
Clinical Project Lead |
| Affiliation |
Sanofi Healthcare India Private Limited |
| Address |
Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai, Mumbai , India
Mumbai
MAHARASHTRA
400 072
India |
| Phone |
919967640071 |
| Fax |
|
| Email |
Vijay.Mandal@sanofi.com |
|
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Source of Monetary or Material Support
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| Sanofi Healthcare India Limited Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai Mumbai:400072 |
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Primary Sponsor
|
| Name |
Sanofi Healthcare India Private Limited |
| Address |
Sanofi House, CTS No.117-B, L&T Business Park, Saki Vihar Road, Powai Mumbai:400072 |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
|
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Countries of Recruitment
|
Argentina
China
India
Israel
Japan
Saudi Arabia
Ukraine
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Kapil Soni |
All India Institute of Medical Sciences (AIIMS) |
Basni, Jodhpur-342005, Rajasthan
Jodhpur
RAJASTHAN |
8003898485
ksoni805@gmail.com |
| Dr Sunil Kumar Kathuria |
Batra Hospital & Medical Research Centre |
Department of ENT, Batra
Hospital and Medical
Research Centre, 1,
Tughlakabad, M. B. Road,
New Delhi- 110062, India
New Delhi
DELHI |
919811215999
kathurias1@rediffmail.com |
| Dr V Venkatraman |
Hindusthan Hospital |
522/3, 523/2, Nava India Road, Udaiyampalayam, Coimbatore, Tamil Nadu-641028, India
Coimbatore
TAMIL NADU |
9176062890
entvenky@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Institutional Human Ethics Committee, All India Institute of Medical Sciences (AIIMS)_ Dr Kapil Soni |
Approved |
| Institutional Human Ethics Committee, Hindusthan Hospital_ Dr V. Venkatraman |
Approved |
| Scientific Research and Ethics Review Committee, Department of Laboratory Medicines, Batra Hospital and Medical Research Centre - Dr. Sunil Kumar Kathuria |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: J308||Other allergic rhinitis, |
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Dupilumab |
Dupilumab 300 mg: a 150 mg/mL dupilumab solution in a pre-filled syringe to deliver 300 mg in a 2 mL injection
Dupilumab 200 mg: a 175 mg/mL dupilumab solution in a pre-filled syringe to deliver 200 mg in a 1.14 mL injection
Unit dose strength(s) 200 and 300 mg/mL
Route of Administration: Sub Cutaneous injection
Total duration of intervention: 52 weeks
|
| Comparator Agent |
Pre-filled syringe (PFS) containing 1.14 mL of Placebo
Pre-filled syringe (PFS) containing 2 mL of Placebo
|
Unit dose strength(s): 0mg/ml
Route of administration: Subcutaneous injection.
Total duration of intervention: 52 weeks
|
|
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Inclusion Criteria
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| Age From |
6.00 Year(s) |
| Age To |
12.00 Year(s) |
| Gender |
Both |
| Details |
Participant must be at least 6 years of age at the time of signing the informed consent.
Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn.
AFRS patients with the following:
An endoscopic NPS of at least 2 out of 4 for unilateral polyps or 3 out of 8 for bilateral polyps at Visit 1 (central reading) and Visit 2 (local reading) and,
Sinus opacification in CT scan with an LMK score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period
Prior sino-nasal surgery(ies) for AFRS
Body weight ≥15 kg
Male and/or female Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
o A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies
Is not a woman of childbearing potential (WOCBP)
Is a WOCBP and agrees to use an acceptable contraceptive method as described in Appendix 4 (Section 10.4) of the protocol during the study (at a minimum until 12 weeks after the last dose of study intervention).
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) on Day 1 before the first dose of study intervention.
If a urine test on Day 1 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.
Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative. For adolescents (≥12 to <18 years) and for children (≥6 to <12 years), both the adolescent/child and the parent/legally authorized representative must sign the specific ICF/assent form |
|
| ExclusionCriteria |
| Details |
Patients with conditions/concomitant diseases making them non-evaluable at Visit 1 or for the primary efficacy endpoint such as:
Antrochoanal polyps.
Nasal septal deviation that would occlude at least one nostril.
Acute sinusitis, nasal infection or upper respiratory infection within 2 weeks prior to Visit 1 (patient can be rescreened after resolution of symptoms).
Ongoing rhinitis medicamentosa.
Eosinophilic granulomatous polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener’s granulomatosis), microscopic polyangiitis, Young’s syndrome,
Kartagener’s syndrome or other dyskinetic ciliary syndromes, cystic fibrosis
Patients with nasal cavity malignant tumor and benign tumors (eg, papilloma, hemangioma, etc)
Known of fungal invasion into sinus tissue.
Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the screening period.
Histories of human immunodeficiency virus (HIV) infection or positive HIV screen (antiHIV-1 and HIV-2 antibodies) serology at the Screening Visit (Visit 1).
Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the patient’s participation in the study. Examples include, but are not limited to participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c ≥9%), participants with cardiovascular conditions (eg, Class III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, participants
on dialysis), hepato-biliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc), other severe endocrinological, gastrointestinal, metabolic, pulmonary, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, electronic case report forms [eCRFs], etc).
Known or suspected history of immunodeficiency, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis), despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.
Patients with active TB or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the patient has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing would be performed on a country by country basis according to local guidelines if required by regulatory authorities or ethic boards.
Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the screening period.
History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
Known or suspected alcohol and/or drug abuse |
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Method of Generating Random Sequence
|
Other |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Participant and Investigator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
To evaluate the ability of dupilumab in reducing the need for rescue therapy in patients with AFRS
Proportion of patients who receive SCS and/or undergo/plan to undergo surgery of AFRS during the planned study treatment period of 52weeks |
52 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To evaluate the efficacy of treatment with dupilumab to
reduce sinus opacification in a population with allergic
fungal rhinosinusitis (AFRS)
Change from baseline in sinus opacifications assessed
by computerized tomography (CT) scans using the Lund
Mackay (LMK) score at Week 52a
Change from baseline in sinus opacifications assessed
by CT scans using the LMK score at Week 24
To assess the efficacy of dupilumab to reduce the need
for rescue treatments:
Proportion of patients who receive SCS during the planned study treatment period.
Proportion of patients who undergo or plan to undergo surgery of AFRS during the planned study treatment period
Total SCS dose, and total number of SCS courses and days during the planned study treatment period
To evaluate the efficacy of treatment with dupilumab in
improving symptoms in AFRS
Change from baseline in monthly average nasal congestion/obstruction score from the Nasal Symptom Diary at Week 24 and Week 52. |
52 weeks |
|
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Target Sample Size
|
Total Sample Size="120"
Sample Size from India="20"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
23/05/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
30/11/2021 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
None yet |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
This
is a Phase 3, multicenter, 52-week treatment, parallel-group, double-blind,
randomized, placebo-controlled study to investigate the efficacy of dupilumab
300 mg every 2 weeks (q2w) for adults and adolescents/children (≥6 to <12
years) ≥60 kg, or dupilumab 200 mg q2w for adolescents/children ≥30 kg and
<60 kg, and dupilumab 300 mg every 4 weeks (q4w) for adolescents/children
≥15 kg and <30 kg with signs and symptoms of AFRS despite prior surgery.
The
study will primarily investigate the effect of dupilumab to reduce need for
repeated SCS and surgery. In addition, the study will also evaluate efficacy of
dupilumab to reduce disease burden in the sinuses (sinus opacification) by
radiographic imaging, nasal polyps, clinical symptoms, and
explore
other measures of disease activity.
The
estimated duration is 4±1 weeks of screening and run-in period, followed by a
3-year double blinded treatment period. There will be a post-treatment
follow-up (FU) period up to 12 weeks
Approximately
120 patients (60 per arm) with AFRS with prior history of surgery will be randomized
in a 1:1 ratio to receive either dupilumab or matching placebo. Randomization
will be
stratified first by
age (adults versus adolescents/children). In adults, randomization will be stratified
further by time from last surgery (≤2 years, >2 years), disease pattern (unilateral/bilateral
in the endoscopy at screening), and country. In adolescents/children, randomization
will not be stratified further |