Clinical Trials List
Protocol NumberR3500-AD-1798
NCT Number(ClinicalTrials.gov Identfier)NCT03736967
2019-07-10 - 2020-02-12
Phase II
Terminated4
ICD-10L20.9
Atopic dermatitis, unspecified
A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Efficacy and Safety of REGN3500 Monotherapy and Combination of REGN3500 Plus Dupilumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis
-
Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
-
Sponsor
Regeneron Pharmaceuticals, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 卓雍哲 Division of Dermatology
- Chih-Chieh Chan Division of Dermatology
- 朱筱桑 Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Hua-En Lee Division of Dermatology
- Chin-Yi Yang Division of Dermatology
- Yih-Shiou Hwang Division of Dermatology
- Chung-Yao Hsu Division of Dermatology
- 林怡廷 Division of Dermatology
- Yu-Huei Huang Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Atopic Dermatitis
Objectives
The primary objective of the study is to evaluate the efficacy of REGN3500 monotherapy compared with placebo treatment in adult patients with moderate-to-severe Atopic dermatitis (AD).
Secondary Objectives are to:
Evaluate the efficacy of REGN3500 in combination with dupilumab compared with placebo treatment in adult patients with moderate-to-severe AD
Assess the safety, tolerability, and immunogenicity of subcutaneous (SC) doses of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD
Evaluate the Pharmacokinetic (PK) of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD
Test Drug
REGN3500 and REGN668 (Dupilumab)
Active Ingredient
REGN3500
REGN668 (Dupilumab)
REGN668 (Dupilumab)
Dosage Form
lyophilized powder for solution for injection
solution for injection
solution for injection
Dosage
287
150
150
Endpoints
Primary Outcome Measures :
Percent change in Eczema Area and Severity Index (EASI) score [ Time Frame: Baseline to week 16 ]
EASI is a composite index with scores ranging from 0 to 72
Secondary Outcome Measures :
Proportion of patients achieving EASI-50 [ Time Frame: Week 16 ]
(≥50% improvement from baseline)
Proportion of patients achieving EASI-75 [ Time Frame: Week 16 ]
(≥75% improvement from baseline)
Proportion of patients achieving EASI-90 [ Time Frame: Week 16 ]
(≥90% improvement from baseline)
Absolute change in EASI score [ Time Frame: From baseline to week 16 ]
EASI is a composite index with scores ranging from 0 to 72
Proportion of patients with an Investigator's Global Assessment (IGA) score of 0 or 1 (on a 5-point scale) [ Time Frame: Week 16 ]
Proportion of patients with an IGA score reduction of ≥2 points [ Time Frame: Week 16 ]
Absolute change in weekly average of daily peak Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 16 ]
Range of 0 (No itch) to 10 (Worst imaginable itch)
Percent change in weekly average of daily peak Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 16 ]
Proportion of patients with improvement (reduction) of weekly average of daily peak Pruritus NRS ≥4 [ Time Frame: Week 16 ]
Time to onset of effect on pruritus [ Time Frame: Baseline to Week 16 ]
≥4-point reduction of weekly average of daily peak Pruritus NRS
Percent change in SCORing Atopic Dermatitis (SCORAD) [ Time Frame: Baseline to Week 16 ]
Change in percent body surface area (BSA) of AD involvement [ Time Frame: Baseline to Week 16 ]
Incidence of treatment-emergent adverse events (TEAEs) from baseline through end of week 16 [ Time Frame: Week 16 ]
Incidence of treatment-emergent SAEs from baseline through end of treatment [ Time Frame: Week 16 ]
Incidence of treatment-emergent adverse events of special interest (AESIs) from baseline through end of treatment [ Time Frame: Week 16 ]
Incidence of TEAEs from baseline through end of study [ Time Frame: Week 36 ]
Incidence of treatment-emergent SAEs from baseline through end of study [ Time Frame: Week 36 ]
Incidence of treatment-emergent AESIs from baseline through end of study [ Time Frame: Week 36 ]
Serum REGN 3500 concentration [ Time Frame: Up to Week 36 ]
Serum dupilumab concentration [ Time Frame: Up to Week 36 ]
Incidence of treatment-emergent anti-drug antibodies to REGN3500 [ Time Frame: Up to Week 36 ]
Incidence of treatment-emergent anti-drug antibodies to dupilumab [ Time Frame: Up to Week 36 ]
Percent change in Eczema Area and Severity Index (EASI) score [ Time Frame: Baseline to week 16 ]
EASI is a composite index with scores ranging from 0 to 72
Secondary Outcome Measures :
Proportion of patients achieving EASI-50 [ Time Frame: Week 16 ]
(≥50% improvement from baseline)
Proportion of patients achieving EASI-75 [ Time Frame: Week 16 ]
(≥75% improvement from baseline)
Proportion of patients achieving EASI-90 [ Time Frame: Week 16 ]
(≥90% improvement from baseline)
Absolute change in EASI score [ Time Frame: From baseline to week 16 ]
EASI is a composite index with scores ranging from 0 to 72
Proportion of patients with an Investigator's Global Assessment (IGA) score of 0 or 1 (on a 5-point scale) [ Time Frame: Week 16 ]
Proportion of patients with an IGA score reduction of ≥2 points [ Time Frame: Week 16 ]
Absolute change in weekly average of daily peak Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 16 ]
Range of 0 (No itch) to 10 (Worst imaginable itch)
Percent change in weekly average of daily peak Pruritus Numerical Rating Scale (NRS) [ Time Frame: Baseline to Week 16 ]
Proportion of patients with improvement (reduction) of weekly average of daily peak Pruritus NRS ≥4 [ Time Frame: Week 16 ]
Time to onset of effect on pruritus [ Time Frame: Baseline to Week 16 ]
≥4-point reduction of weekly average of daily peak Pruritus NRS
Percent change in SCORing Atopic Dermatitis (SCORAD) [ Time Frame: Baseline to Week 16 ]
Change in percent body surface area (BSA) of AD involvement [ Time Frame: Baseline to Week 16 ]
Incidence of treatment-emergent adverse events (TEAEs) from baseline through end of week 16 [ Time Frame: Week 16 ]
Incidence of treatment-emergent SAEs from baseline through end of treatment [ Time Frame: Week 16 ]
Incidence of treatment-emergent adverse events of special interest (AESIs) from baseline through end of treatment [ Time Frame: Week 16 ]
Incidence of TEAEs from baseline through end of study [ Time Frame: Week 36 ]
Incidence of treatment-emergent SAEs from baseline through end of study [ Time Frame: Week 36 ]
Incidence of treatment-emergent AESIs from baseline through end of study [ Time Frame: Week 36 ]
Serum REGN 3500 concentration [ Time Frame: Up to Week 36 ]
Serum dupilumab concentration [ Time Frame: Up to Week 36 ]
Incidence of treatment-emergent anti-drug antibodies to REGN3500 [ Time Frame: Up to Week 36 ]
Incidence of treatment-emergent anti-drug antibodies to dupilumab [ Time Frame: Up to Week 36 ]
Inclution Criteria
1. Male or female, 18 to 75 years
2. Chronic AD, according to American Academy of Dermatology Consensus Criteria
(Eichenfield, 2014), that has been present for at least 3 years before the screening visit
3. EASI score ≥16 at the screening and baseline visits
4. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening
and baseline visits
5. ≥10% BSA of AD involvement at the screening and baseline visits
6. Baseline peak Pruritus NRS score for maximum itch intensity ≥4
NOTE: Baseline peak Pruritus NRS score for maximum itch intensity will be determined
based on the average of daily NRS scores for maximum itch intensity (the daily score
ranges from 0 to 10) during the 7 days immediately preceding randomization. A minimum
of 4 daily scores out of the 7 days is required to calculate the baseline average score. For
patients who do not have at least 4 daily scores reported during the 7 days immediately
preceding the planned randomization date, randomization should be postponed until this
requirement is met, but without exceeding the 35-day maximum duration for screening.
7. Documented recent history (within 6 months before the screening visit) of inadequate
response to topical AD medication(s) or for whom topical treatments are medically
inadvisable (eg, intolerance, because of important side effects, or safety risks).
8. Have applied a stable dose of topical bland emollient (moisturizer) at least twice daily for
at least the 7 consecutive days immediately before randomization
(ie, baseline/randomization visit would be the eighth day; see exclusion criterion 7
regarding restrictions on the kind of emollients permitted during the study).
9. Willing and able to comply with all clinic visits and study-related procedures
10. Provide informed consent signed by study patient or legally acceptable representative
11. Able to understand and complete study-related questionnaires
2. Chronic AD, according to American Academy of Dermatology Consensus Criteria
(Eichenfield, 2014), that has been present for at least 3 years before the screening visit
3. EASI score ≥16 at the screening and baseline visits
4. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening
and baseline visits
5. ≥10% BSA of AD involvement at the screening and baseline visits
6. Baseline peak Pruritus NRS score for maximum itch intensity ≥4
NOTE: Baseline peak Pruritus NRS score for maximum itch intensity will be determined
based on the average of daily NRS scores for maximum itch intensity (the daily score
ranges from 0 to 10) during the 7 days immediately preceding randomization. A minimum
of 4 daily scores out of the 7 days is required to calculate the baseline average score. For
patients who do not have at least 4 daily scores reported during the 7 days immediately
preceding the planned randomization date, randomization should be postponed until this
requirement is met, but without exceeding the 35-day maximum duration for screening.
7. Documented recent history (within 6 months before the screening visit) of inadequate
response to topical AD medication(s) or for whom topical treatments are medically
inadvisable (eg, intolerance, because of important side effects, or safety risks).
8. Have applied a stable dose of topical bland emollient (moisturizer) at least twice daily for
at least the 7 consecutive days immediately before randomization
(ie, baseline/randomization visit would be the eighth day; see exclusion criterion 7
regarding restrictions on the kind of emollients permitted during the study).
9. Willing and able to comply with all clinic visits and study-related procedures
10. Provide informed consent signed by study patient or legally acceptable representative
11. Able to understand and complete study-related questionnaires
Exclusion Criteria
1. Prior participation in a REGN3500 (anti-IL-33) or dupilumab (anti-IL-4Rα) clinical study;
past treatment with or current treatment with dupilumab
2. Body mass index <16 kg/m2
3. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known),
whichever is longer, before the baseline visit
4. Having used any of the following treatments within 4 weeks before the baseline visit or
any condition that, in the opinion of the investigator, is likely to require such treatment(s)
during the first 4 weeks of study treatment:
Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids,
cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine,
methotrexate, etc)
Phototherapy for AD
5. Treatment with TCS, TCI, or topical crisaborole within 1 week before the baseline visit
6. Treatment with biologics as follows:
Any cell-depleting agents including but not limited to rituximab: within 6 months
before the baseline visit, or until lymphocyte count returns to normal, whichever is
longer
Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit,
whichever is longer
7. Initiation of treatment of AD with prescription moisturizers or moisturizers containing
additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during
the screening period (patients may continue using stable doses of such moisturizers if
initiated before the screening visit)
8. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the
baseline visit
9. Planned or anticipated use of any prohibited medications and procedures during study
treatment
10. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
11. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals,
antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or
superficial skin infections within 1 week before the baseline visit
12. Known or suspected history of immunosuppression, including history of invasive
opportunistic infections (eg, tuberculosis [TB]*, histoplasmosis, listeriosis,
coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or
unusually frequent, recurrent, or prolonged infections, per investigator judgment
*Patients with a positive TB QuantiFERON test result at screening will be excluded from
the study.
13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at
screening
14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or
hepatitis C virus antibody (HCV Ab) at the screening visit
15. At baseline, presence of any conditions listed as criteria for study drug discontinuation
16. Presence of skin comorbidities that may interfere with study assessments
17. History of cancer, with the exceptions of:
Patients with adequately treated basal cell carcinoma or carcinoma in situ of the cervix.
Patients with other malignancies that have been successfully treated for >10 years prior
to screening where, in the judgement of both the investigator and the treating physician,
appropriate follow-up has revealed no evidence of recurrence through time of
screening.
18. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic
infection, unless clinical and (if necessary) laboratory assessment have ruled out active
infection before randomization
19. History of alcohol or drug abuse within 2 years of the screening visit
20. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect
the patient’s participation in the study.
21. Any other medical or psychological condition (including relevant laboratory abnormalities
at screening) that, in the opinion of the investigator, may suggest a new and/or
insufficiently understood disease, may present an unreasonable risk to the study patient as
a result of his/her participation in this clinical study, may make patient’s participation
unreliable, or may interfere with study assessments. The specific justification for patients
excluded under this criterion will be noted in study documents (chart notes, CRFs, etc).
22. Planned or anticipated major surgical procedure during the patient’s participation in this
study
23. Patient is a member of the investigational team or his/her immediate family
24. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
during the study
25. Women of childbearing potential (WOCBP)* who are unwilling to practice highly
effective contraception prior to the initial dose/start of the first treatment, during the study,
and for at least 20 weeks after the last dose of study drug. Highly effective contraceptive
measures include:
a. stable use of oral contraceptives associated with inhibition of ovulation (such as
contraceptives containing estrogen/progesterone or high dose progesterone) initiated
2 or more menstrual cycles prior to screening
b. intrauterine device (IUD); intrauterine hormone releasing system (IUS)
c. bilateral tubal ligation
d. vasectomized partner with confirmed sterility (ie, patient’s medical record)
e. and/or sexual abstinence†, ‡
f. contraception for male patients is not required§
26. Known sensitivity to doxycycline and/or tetracycline or to any of the components of the
investigational product formulation
27. Patients who are committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities will be excluded from this study (as required by
country regulations).
past treatment with or current treatment with dupilumab
2. Body mass index <16 kg/m2
3. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known),
whichever is longer, before the baseline visit
4. Having used any of the following treatments within 4 weeks before the baseline visit or
any condition that, in the opinion of the investigator, is likely to require such treatment(s)
during the first 4 weeks of study treatment:
Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids,
cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine,
methotrexate, etc)
Phototherapy for AD
5. Treatment with TCS, TCI, or topical crisaborole within 1 week before the baseline visit
6. Treatment with biologics as follows:
Any cell-depleting agents including but not limited to rituximab: within 6 months
before the baseline visit, or until lymphocyte count returns to normal, whichever is
longer
Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit,
whichever is longer
7. Initiation of treatment of AD with prescription moisturizers or moisturizers containing
additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during
the screening period (patients may continue using stable doses of such moisturizers if
initiated before the screening visit)
8. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the
baseline visit
9. Planned or anticipated use of any prohibited medications and procedures during study
treatment
10. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
11. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals,
antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or
superficial skin infections within 1 week before the baseline visit
12. Known or suspected history of immunosuppression, including history of invasive
opportunistic infections (eg, tuberculosis [TB]*, histoplasmosis, listeriosis,
coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or
unusually frequent, recurrent, or prolonged infections, per investigator judgment
*Patients with a positive TB QuantiFERON test result at screening will be excluded from
the study.
13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at
screening
14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or
hepatitis C virus antibody (HCV Ab) at the screening visit
15. At baseline, presence of any conditions listed as criteria for study drug discontinuation
16. Presence of skin comorbidities that may interfere with study assessments
17. History of cancer, with the exceptions of:
Patients with adequately treated basal cell carcinoma or carcinoma in situ of the cervix.
Patients with other malignancies that have been successfully treated for >10 years prior
to screening where, in the judgement of both the investigator and the treating physician,
appropriate follow-up has revealed no evidence of recurrence through time of
screening.
18. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic
infection, unless clinical and (if necessary) laboratory assessment have ruled out active
infection before randomization
19. History of alcohol or drug abuse within 2 years of the screening visit
20. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect
the patient’s participation in the study.
21. Any other medical or psychological condition (including relevant laboratory abnormalities
at screening) that, in the opinion of the investigator, may suggest a new and/or
insufficiently understood disease, may present an unreasonable risk to the study patient as
a result of his/her participation in this clinical study, may make patient’s participation
unreliable, or may interfere with study assessments. The specific justification for patients
excluded under this criterion will be noted in study documents (chart notes, CRFs, etc).
22. Planned or anticipated major surgical procedure during the patient’s participation in this
study
23. Patient is a member of the investigational team or his/her immediate family
24. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
during the study
25. Women of childbearing potential (WOCBP)* who are unwilling to practice highly
effective contraception prior to the initial dose/start of the first treatment, during the study,
and for at least 20 weeks after the last dose of study drug. Highly effective contraceptive
measures include:
a. stable use of oral contraceptives associated with inhibition of ovulation (such as
contraceptives containing estrogen/progesterone or high dose progesterone) initiated
2 or more menstrual cycles prior to screening
b. intrauterine device (IUD); intrauterine hormone releasing system (IUS)
c. bilateral tubal ligation
d. vasectomized partner with confirmed sterility (ie, patient’s medical record)
e. and/or sexual abstinence†, ‡
f. contraception for male patients is not required§
26. Known sensitivity to doxycycline and/or tetracycline or to any of the components of the
investigational product formulation
27. Patients who are committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities will be excluded from this study (as required by
country regulations).
The Estimated Number of Participants
-
Taiwan
18 participants
-
Global
405 participants
