A long-term extension study to evaluate the long-term safety, tolerability and efficacy of subcutaneous amlitelimab in participants of previous amlitelimab clinical trials in moderate to severe atopic dermatitis
Long-Term Safety and Efficacy Evaluation of amlitelimab in participants of previous amlitelimab moderate to severe atopic dermatitis clinical trials (RIVER-AD)
Obara Kentaro
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-363013670
clinical-trials-jp@sanofi.com
Clinical Study Unit
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-363013670
clinical-trials-jp@sanofi.com
Not Recruiting
Jan. 01, 2023
Jan. 06, 2023
1663
Interventional
single arm study
open(masking not used)
uncontrolled control
parallel assignment
treatment purpose
- Participant must be at least 12 years of age inclusive at the time of signing the informed consent.
- Participated in an amlitelimab clinical trial for moderate to severe AD and received study treatment, adequately completed the assessments required for the treatment period.
- - Have reached the rollover timepoint to LTS17367 at the last visit of the treatment period of their feeder study SFY17915, INT18404, EFC17599, or EFC17600
- - Participants in DRI17366 must only be enrolled from 1 of the following 3 groups:
- - - The first group: participants at Week 24 in the DRI17336 study who have not achieved an >= Eczema Area and Skin Severity Index (EASI)-75 and are Investigator Global Assessment (IGA) >=2.
- - - The second group: participants entering LTS17367 between Week 28 and Week 52 of the feeder study, due to loss of clinical response in the part 2 of the feeder study. Timepoints for entering LTS17367 are Weeks 28, 32, 36, 40, 44, 48 or 52.
- - - The third group: participants at Week 24 in DRI17336 who have been re-randomized and who subsequently complete the study to Week 52, enter safety follow-up and experience worsening of their AD during safety follow-up
- - Participated in DRI17366 completing the previous study safety follow up (Week 68) and wish to re-initiate treatment with amlitelimab up to one year after the last visit
- Complied with the previous clinical trial protocol to the satisfaction of the investigator
- Body weight must be >= 25 kg
- Provided signed informed assent/or consent and able to comply with the requirements of the protocol
Participants are excluded from the study if any of the following criteria apply:
- Developed a medical condition that would preclude participation as described in the section for permanent discontinuation of the feeder study or LTS17367 protocol
- Known history of or suspected current significant immunosuppression, including history of invasive opportunistic infections or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration
- History of solid organ or stem cell transplant
- Any malignancies or history of malignancies prior to baseline (except for non-melanoma skin cancer that has been excised and completely cured for more than 5 years prior to baseline)
- Participants positive for human immunodeficiency virus (HIV); participants with any of the following results at Screening (Visit 1) or at any point during the feeder study: presence of hepatitis B surface antigen (HBsAg) with or without hepatitis B virus (HBV)-
deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test, or presence of antibody to hepatitis B core antigen (HBcAb) or presence of antibody to hepatitis B
surface antigen (HBsAb) with positive HBV DNA PCR test; positive hepatitis C total antibody (HCVAb) confirmed by positive hepatitis C virus ribonucleic acid (HCV RNA) PCR test
- History (within last 2 years prior to baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator
- Participants with active tuberculosis(TB), latent TB, a history of incompletely treated TB, suspected extrapulmonary TB infection, non-TB mycobacterial infection, or who are at high risk of contracting TB (such as close contact with individuals with active or latent TB) or received Bacillus Calmette-Guerin (BCG)-vaccination within 12 weeks prior to screening
- Participants with an indeterminate or a confirmed positive QuantiFERON -Tuberculosis Gold interferon-gamma release assay (IGRA) test are excluded from the study unless all of the following conditions are met:
1. Have a history of prior documented completed chemoprophylaxis for latent TB infection (with a treatment regimen as per local guidelines), OR treated for active TB infection
2. Have been in written form approved for participation in the present trial by a TB specialist who ruled out latent or active TB infection or other mycobacterial infection in the participant
3. For whom review and approval from Sponsor have been granted are eligible
- Severe concomitant illness that would in the Investigator's opinion inhibit the participant's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease
- Skin co-morbidity that would adversely affect the ability to undertake AD assessments (e.g., psoriasis, tinea corporis, lupus erythematosus) as per Investigator's judgment
- Any medical condition which, in the opinion of the Investigator may present an unreasonable risk to the study participant as a result of his/her participation in this clinical study, may make participant's participation unreliable, or may interfere with study assessments
- In the Investigator's opinion, medical conditions related to prior AD medications that have not healed/fully recovered for more than 2 weeks before screening visit, including, but not limited to, conjunctivitis, keratitis, eosinophilic conditions, arthralgia, herpes zoster, thrombosis
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
12age old over
No limit
Both
Dermatitis atopic
Drug: Amlitelimab (SAR445229)
Pharmaceutical form: Solution for injection, Route of administration: Subcutaneous
Drug: Topical corticosteroids
Pharmaceutical form: Topical, Route of administration: Topical
Drug: Topical calcineurin inhibitors
Pharmaceutical form: Topical. Route of administration: Topical
Drug: Oral corticosteroids
Pharmaceutical form: Oral, Route of administration: Oral
1. Percentage of participants who experienced treatment-emergent adverse event (TEAE)
[Time Frame: Baseline to Week 332]
1. Percentage of participants who experienced treatment-emergent serious adverse events (SAEs)
[Time Frame: Baseline to Week 332]
2. Percentage of participants who experienced treatment-emergent adverse events of special interest (AESI)
[Time Frame: Baseline to Week 332]
3. Percentage of participants who experienced treatment-emergent adverse events (TEAEs) leading to treatment discontinuation
[Time Frame: Baseline to Week 332]
4. Absolute change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24
[Time Frame: DRI17366 Baseline to Week 332]
*1) EASI measures the severity & extent of AD based on 4 AD disease characteristics (erythema, thickness [induration, papulation, edema], scratching [excoriation] & lichenification). Total score ranges from 0 (minimum) to 72 (maximum), higher scores indicated greater severity of AD.
5. Percent change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24
[Time Frame: DRI17366 Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1)"
6. Proportion of participants with EASI50/EASI75/EASI90/EASI100 from DRI17366 baseline at each LTS17367 visit in participants entering the study from DRI17366 Week 24
[Time Frame: DRI17366 Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1)"
EASI50: >= 50% reduction in score from baseline; EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline.
7. Proportion of participants with a response of Validated Investigator Global Assessment scale for atopic dermatitis (vIGA-AD) 0 or 1 at each LTS17367 visit in participants entering the study from DRI17366 Week 24
[Time Frame: Baseline to Week 332]
*2) The vIGA-AD is an assessment instrument used to rate the severity of AD globally, based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity.
8. Proportion of participants with vIGA-AD score 0/1 in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
For vIGA-AD, see "Secondary Outcome-7. *2)"
9. Proportion of participants with vIGA-AD score 0 [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
For vIGA-AD, see "Secondary Outcome-7. *2)"
10. Proportion of participants with vIGA-AD score 0 or 1 with presence of only barely perceptible erythema (no induration/papulation, no lichenification, no oozing or crusting) at each LTS17367 visit
[Time Frame: Baseline to Week 332]
For vIGA-AD, see "Secondary Outcome-7. *2)"
11. Time to first vIGA-AD 0/1 after LTS17367 enrollment in those participants who had not achieved vIGA-AD 0/1 by the time of LTS17367 enrollment
[Time Frame: Baseline to Week 332]
For vIGA-AD, see "Secondary Outcome-7. *2)"
12. Absolute change from feeder study baseline in EASI score in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1)"
13. Percent change from feeder study baseline in EASI score in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1"
14. Proportion of participants with EASI50/EASI75/EASI90 in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1"
EASI50: >= 50% reduction in score from baseline; EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline.
15. Time to first EASI75/EASI90 in those participants who had not achieved it by the time of LTS17367 enrollment
[Time Frame: Baseline to Week 332]
For EASI, see "Secondary Outcome-4. *1"
EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline.
16. Proportion of participants requiring topical treatment in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
17. Proportion of participants requiring rescue treatment [each LTS17367 visit] all treatments in all participants entering the study
[Time Frame: Baseline to Week 332]
18. Number of days on topical medication (per patient-year) in all participants entering the study
[Time Frame: Baseline to Week 332]
19. Change from feeder study baseline atopic dermatitis control tool (ADCT) in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
ADCT is a six-item patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control. The score ranges from 0-24 with higher scores indicate worsening disease control.
20. Change from feeder study baseline in dermatology life quality index (DLQI/cDLQI) in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
The children's DLQI (cDLQI) measures dermatology specific quality of life (QoL) in children patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
21. Change from feeder study baseline in patient oriented eczema measure (POEM) in all participants entering the study [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life.
22. Change from feeder study baseline in body surface area affected by AD (BSA-AD) [each LTS17367 visit]
[Time Frame: Baseline to Week 332]
23. Time from enrollment in LTS17367 to first loss of vIGA-AD 0 in those participants who were vIGA-AD 0 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
[Time Frame: Baseline to Week 332]
24. Time from enrollment in LTS17367 to first loss EASI75 in those participants who had reached EASI75 at LTS17367 rollover coming from EFC17600 (ESTUARY) and EFC17599 (AQUA)
[Time Frame: Baseline to Week 332]
25. Time from enrollment in LTS17367 to first loss of vIGA-AD 0/1 in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
[Time Frame: Baseline to Week 332]
26. Time from LTS17367 baseline to re-treatment with amlitelimab in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
[Time Frame: Baseline to Week 332]
27. Time from last amlitelimab dose in feeder study to re-treatment with amlitelimab in those participants who were vIGA-AD 0/1 at LTS17367 rollover from EFC17600 (ESTUARY) and EFC17599 (AQUA)
[Time Frame: Baseline to Week 332]
28. Serum amlitelimab concentration assessed at prespecified time points through the end of the study
[Time Frame: Baseline to Week 332]
29. Number of participants with anti-drug antibody response (ADAs) of amlitelimab at prespecified timepoints
[Time Frame: Baseline to Week 332]
Sanofi K.K.
Medical Corporation Shintokai Yokohama Minoru Clinic Institutional Review Board
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
NCT05492578
ClinicalTrials.gov
2021-002344-73
EudraCT
2023-506548-18
CTIS
Australia/Bulgaria/Hungary/Poland/Spain/United States/Argentina/Brazil/Canada/Chile/China/Czechia/France/Greece/Germany/Israel/Italy/South Korea/Taiwan/Turkey/United Arab Emirates/United Kingdom/Saudi Arabia/South Africa/Denmark/India/Mexico/Portugal
