Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis
Primary Purpose
Atopic Dermatitis
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Rilzabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis
Eligibility Criteria
Inclusion Criteria:
- AD as defined by the American Academy of Dermatology Consensus Criteria.
- History of AD for at least 12 months prior to baseline as determined by the Investigator through patient interview.
- Eczema Area and Severity Index (EASI) score ≥ 12 at screening and at baseline.
- IGA score ≥ 3 (on the 0 to 4 IGA scale) at baseline.
- BSA of AD involvement ≥ 10% at baseline.
- Documented inadequate response or intolerance to TCS within 6 months prior to baseline visit
- Baseline PP-NRS score for maximum itch intensity ≥4.
- All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- For optional substudy only: Willingness to have 2 tape strips for comparison of baseline and treatment response.
Exclusion Criteria:
- Skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus.
- Conditions that may predispose the patient to excessive bleeding.
- Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.
- Laboratory abnormalities at the screening visit
- History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by the Site Investigator and the Sponsor Medical Monitor), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19).
- Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
- COVID-19 vaccine within 14 days prior to Study Day 1.
- Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
- Initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period.
- Use of TCS, topical calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication.
- Use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication.
- Phototherapy for AD or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study.
- Use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kineret (anakinra), Enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline.
- Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IFN-γ, JAK inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline.
- Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented B cell reconstitution for anti-CD20 drugs).
- Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to H2 receptor blocking drugs prior to baseline).
- Concomitant use of known systemic strong-to-moderate inhibitors and inducers of cytochrome P450 3A (CYP3A) within 14 days or 5 half-lives (whichever is longer) prior to baseline.
- Previous use of a BTK inhibitor.
- Has received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer).
- Active TB or a history of incompletely treated TB, Quantiferon positive patients, Clinically significant abnormality consistent with prior/active TB infection based upon chest radiograph with at least posterior-anterior view, Suspected extrapulmonary TB infection, or patients at high risk of contracting TB.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Antelope Valley Clinical Trials-Site Number:8400001
- Therapeutics Clinical Research-Site Number:8400010
- Asthma and Allergy Associates, PC-Site Number:8400008
- Florida International Research Center-Site Number:8400002
- Skin Sciences, PLLC-Site Number:8400005
- Dermatologist Specialist-Site Number:8400004
- Integrative Skin Care of MS/SKYCRNG-Site Number:8400011
- National Allergy and Asthma Research, LLC.-Site Number:8400007
- Orion Clinical Research-Site Number:8400003
- E.P.I.M.R.D dba Western Sky Research, Inc.-Site Number:8400009
- Investigational Site Number :1240008
- Investigational Site Number :1240001
- Investigational Site Number :1240002
- Investigational Site Number :1240013
- Investigational Site Number :1240011
- Investigational Site Number :1240007
- Investigational Site Number :1240004
- Investigational Site Number :1520004
- Investigational Site Number :1520001
- Investigational Site Number :1520002
- Investigational Site Number :2030004
- Investigational Site Number :2030003
- Investigational Site Number :2030002
- Investigational Site Number :2030001
- Investigational Site Number :2760001
- Investigational Site Number :2760002
- Investigational Site Number :2760003
- Investigational Site Number :5280001
- Investigational Site Number :6160001
- Investigational Site Number :6160005
- Investigational Site Number :6160007
- Investigational Site Number :6160008
- Investigational Site Number :6160002
- Investigational Site Number :6160004
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rilzabrutinib
Placebo
Arm Description
Rilzabrutinib BID or TID
Matching placebo
Outcomes
Primary Outcome Measures
Percent change in Eczema Area and Severity Index (EASI) score
The EASI is a composite index with scores ranging from 0 to 72. A higher score means more severe condition.
Secondary Outcome Measures
Proportion of participants with Investigator's Global Assessment (IGA) of 0 or 1 (disease free or almost disease free) compared to placebo
Proportion of participants achieving EASI-75
Defined as reduction of EASI score by ≥75% from baseline
Proportion of participants with reduction of weekly average of daily peak pruritus Numerical Rating Scale (PP-NRS) of ≥4 points
Time to onset of effect on pruritus
Defined as ≥4 points reduction of weekly average of daily PP-NRS from baseline during the 16-week treatment period
Absolute change in EASI score
Proportion of participants achieving EASI-50/90
Defined as reduction of EASI score by ≥50% or ≥90% from baseline
Change in percent body surface area (BSA) of EASI
Change on weekly average of daily PP-NRS
Based on daily participant assessments documented in their electronic diary
Proportion of participants achieving IGA*BSA-50/75/90 (reduction of IGA*BSA by ≥50% or 75% or 90% from baseline) at Week 16
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05018806
Brief Title
Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis
Official Title
A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Proof-of-concept Study Evaluating Efficacy and Safety of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis Who Are Inadequate Responders or Intolerant to Topical Corticosteroids
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
June 23, 2023 (Actual)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a parallel, treatment, Phase 2, double-blind, 2-arm, placebo-controlled study with 2 staggered cohorts (2 arms in each cohort) to evaluate the efficacy and safety of rilzabrutinib in adult participants (aged at least 18 years) with moderate-to-severe AD and intolerance or inadequate response to topical corticosteroids (TCS). In parallel to the main study, Japanese participants will be enrolled in a separate sub-study and randomized to receive: Rilzabrutinib TID, Rilzabrutinib BID, or Matching Placebo TID.
The total study duration per participant is expected to be approximately 21 weeks, including up to 4 weeks of screening, 16 weeks of on-treatment double-blind period, 1 week of post-treatment follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
124 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rilzabrutinib
Arm Type
Experimental
Arm Description
Rilzabrutinib BID or TID
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: Tablet Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Rilzabrutinib
Other Intervention Name(s)
PRN1008/SAR444671
Intervention Description
Pharmaceutical form: Tablet Route of administration: Oral
Primary Outcome Measure Information:
Title
Percent change in Eczema Area and Severity Index (EASI) score
Description
The EASI is a composite index with scores ranging from 0 to 72. A higher score means more severe condition.
Time Frame
From baseline to Week 16
Secondary Outcome Measure Information:
Title
Proportion of participants with Investigator's Global Assessment (IGA) of 0 or 1 (disease free or almost disease free) compared to placebo
Time Frame
At Week 16
Title
Proportion of participants achieving EASI-75
Description
Defined as reduction of EASI score by ≥75% from baseline
Time Frame
At Week 16
Title
Proportion of participants with reduction of weekly average of daily peak pruritus Numerical Rating Scale (PP-NRS) of ≥4 points
Time Frame
From baseline to Week 16
Title
Time to onset of effect on pruritus
Description
Defined as ≥4 points reduction of weekly average of daily PP-NRS from baseline during the 16-week treatment period
Time Frame
Until Week 16
Title
Absolute change in EASI score
Time Frame
From baseline to Week 16
Title
Proportion of participants achieving EASI-50/90
Description
Defined as reduction of EASI score by ≥50% or ≥90% from baseline
Time Frame
At Week 16
Title
Change in percent body surface area (BSA) of EASI
Time Frame
From baseline to Week 16
Title
Change on weekly average of daily PP-NRS
Description
Based on daily participant assessments documented in their electronic diary
Time Frame
From baseline to Week 16
Title
Proportion of participants achieving IGA*BSA-50/75/90 (reduction of IGA*BSA by ≥50% or 75% or 90% from baseline) at Week 16
Time Frame
At Week 16
Title
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Time Frame
Up to Week 17
Title
Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs
Time Frame
From baseline to Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
AD as defined by the American Academy of Dermatology Consensus Criteria.
History of AD for at least 12 months prior to baseline as determined by the Investigator through patient interview.
Eczema Area and Severity Index (EASI) score ≥ 12 at screening and at baseline.
IGA score ≥ 3 (on the 0 to 4 IGA scale) at baseline.
BSA of AD involvement ≥ 10% at baseline.
Documented inadequate response or intolerance to TCS within 6 months prior to baseline visit
Baseline PP-NRS score for maximum itch intensity ≥4.
All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
For optional substudy only: Willingness to have 2 tape strips for comparison of baseline and treatment response.
Exclusion Criteria:
Skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus.
Conditions that may predispose the patient to excessive bleeding.
Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.
Laboratory abnormalities at the screening visit
History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by the Site Investigator and the Sponsor Medical Monitor), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19).
Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
COVID-19 vaccine within 14 days prior to Study Day 1.
Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
Initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period.
Use of TCS, topical calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication.
Use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication.
Phototherapy for AD or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study.
Use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kineret (anakinra), Enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline.
Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IFN-γ, JAK inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline.
Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented B cell reconstitution for anti-CD20 drugs).
Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to H2 receptor blocking drugs prior to baseline).
Concomitant use of known systemic strong-to-moderate inhibitors and inducers of cytochrome P450 3A (CYP3A) within 14 days or 5 half-lives (whichever is longer) prior to baseline.
Previous use of a BTK inhibitor.
Has received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer).
Active TB or a history of incompletely treated TB, Quantiferon positive patients, Clinically significant abnormality consistent with prior/active TB infection based upon chest radiograph with at least posterior-anterior view, Suspected extrapulmonary TB infection, or patients at high risk of contracting TB.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Facility Information:
Facility Name
Antelope Valley Clinical Trials-Site Number:8400001
City
Northridge
State/Province
California
ZIP/Postal Code
91325
Country
United States
Facility Name
Therapeutics Clinical Research-Site Number:8400010
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Asthma and Allergy Associates, PC-Site Number:8400008
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Florida International Research Center-Site Number:8400002
City
Miami
State/Province
Florida
ZIP/Postal Code
33173
Country
United States
Facility Name
Skin Sciences, PLLC-Site Number:8400005
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40217
Country
United States
Facility Name
Dermatologist Specialist-Site Number:8400004
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40241
Country
United States
Facility Name
Integrative Skin Care of MS/SKYCRNG-Site Number:8400011
City
Ridgeland
State/Province
Mississippi
ZIP/Postal Code
39157
Country
United States
Facility Name
National Allergy and Asthma Research, LLC.-Site Number:8400007
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29420
Country
United States
Facility Name
Orion Clinical Research-Site Number:8400003
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Facility Name
E.P.I.M.R.D dba Western Sky Research, Inc.-Site Number:8400009
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States
Facility Name
Investigational Site Number :1240008
City
Red Deer
State/Province
Alberta
ZIP/Postal Code
T4P 1K4
Country
Canada
Facility Name
Investigational Site Number :1240001
City
London
State/Province
Ontario
ZIP/Postal Code
N6A2C2
Country
Canada
Facility Name
Investigational Site Number :1240002
City
Markham
State/Province
Ontario
ZIP/Postal Code
L3P 1X2
Country
Canada
Facility Name
Investigational Site Number :1240013
City
Sudbury
State/Province
Ontario
ZIP/Postal Code
P3E 5M4
Country
Canada
Facility Name
Investigational Site Number :1240011
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M2N 3A6
Country
Canada
Facility Name
Investigational Site Number :1240007
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3H 5Y8
Country
Canada
Facility Name
Investigational Site Number :1240004
City
Quebec
ZIP/Postal Code
G1V 4T3
Country
Canada
Facility Name
Investigational Site Number :1520004
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7580206
Country
Chile
Facility Name
Investigational Site Number :1520001
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7640881
Country
Chile
Facility Name
Investigational Site Number :1520002
City
Santiago
State/Province
Reg Metropolitana De Santiago
Country
Chile
Facility Name
Investigational Site Number :2030004
City
Olomouc
ZIP/Postal Code
779 00
Country
Czechia
Facility Name
Investigational Site Number :2030003
City
Pardubice
ZIP/Postal Code
53002
Country
Czechia
Facility Name
Investigational Site Number :2030002
City
Plzen
ZIP/Postal Code
30599
Country
Czechia
Facility Name
Investigational Site Number :2030001
City
Praha 6
ZIP/Postal Code
160 00
Country
Czechia
Facility Name
Investigational Site Number :2760001
City
Bad Bentheim
ZIP/Postal Code
48455
Country
Germany
Facility Name
Investigational Site Number :2760002
City
Friedrichshafen
ZIP/Postal Code
88045
Country
Germany
Facility Name
Investigational Site Number :2760003
City
Osnabrück
ZIP/Postal Code
49074
Country
Germany
Facility Name
Investigational Site Number :5280001
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Investigational Site Number :6160001
City
Lodz
State/Province
Lódzkie
ZIP/Postal Code
90-436
Country
Poland
Facility Name
Investigational Site Number :6160005
City
Gdansk
State/Province
Pomorskie
ZIP/Postal Code
80-546
Country
Poland
Facility Name
Investigational Site Number :6160007
City
Bydgoszcz
ZIP/Postal Code
85-796
Country
Poland
Facility Name
Investigational Site Number :6160008
City
Chojnice
ZIP/Postal Code
89600
Country
Poland
Facility Name
Investigational Site Number :6160002
City
Lodz
ZIP/Postal Code
93-530
Country
Poland
Facility Name
Investigational Site Number :6160004
City
Warszawa
ZIP/Postal Code
00-215
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Links:
URL
https://www.sanofistudies.com/eczema
Description
ACT17207 Moderate-to-severe Atopic Dermatitis website
Learn more about this trial
Proof of Concept Study of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis
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