Long-Term Safety and Efficacy Evaluation of Amlitelimab in Participants of Previous Amlitelimab Moderate to Severe Atopic Dermatitis Clinical Trials

Dermatitis Atopic Clinical Trial

— RIVER-AD  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05492578
• Other study ID #: LTS17367
• Secondary ID: U1111-1269-64902
• Status: Recruiting
• Phase: Phase 2
• Start date: August 22, 2022
• Est. completion date: April 18, 2028

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single group, Phase 2, long-term extension study for treatment. The purpose of this study is to characterize the safety and efficacy of amlitelimab in treated adult participants with moderate to severe AD who have previously been enrolled in an amlitelimab clinical trial. Visits during the on-treatment period will be at Week 0, 1, 2, 4 and every 4 weeks (Q4W) thereafter. If remote visits are considered appropriate for participants instead of clinic visits at the timepoints indicated in the schedule of activities (SoA) participants/caregivers/legally authorized representatives (LAR) are allowed to perform participant-injections at home according to the schedule of dosing. This decision is at the discretion of the investigator.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: April 18, 2028
• Est. primary completion date: October 29, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: - Participant must be 18 years of age, inclusive, or older 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 parent study SFY17915

• 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 parent study, due to loss of clinical response in the part 2 of the parent study. Timepoints for entering LTS17367 are Weeks 28, 32, 36, 40, 44, 48 or 52. For DRI17366 loss of clinical response is defined as the first instance of < EASI 50 during the second study period and where rescue therapy is no longer permitted.

• The third group: participants at Week 24 in DRI17366 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 or thereafter

• Provide signed informed consent and able to comply with the requirements of the protocol Exclusion Criteria:

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 permanent discontinuation

• Known history of or suspected significant current 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; participants with any of the following results at Screening (Visit 1) or at any point during the parent study: presence of HBsAg with or without HBV DNA PCR test, or presence of anti-HBc Ab or presence of anti-HBs Ab with positive HBV DNA PCR test; positive HCVAb confirmed by positive HCV RNA

• History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator

• Participants with active 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-Guérin (BCG)-vaccination within 12 weeks prior to screening

• Participants with an intermediate or a positive 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 patient'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

• Any medical or psychiatric condition which, in the opinion of the Investigator 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

• 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

Related Conditions & MeSH terms

• Dermatitis
• Dermatitis Atopic
• Dermatitis, Atopic

Intervention

Drug:
• Amlitelimab
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Other:
• Topical corticosteroids
Pharmaceutical form: Topical Route of administration: Topical
• Topical calcineurin inhibitors
Pharmaceutical form: Topical Route of administration: Topical
• Oral corticosteroids
Pharmaceutical form: Oral Route of administration: Oral

Locations

Country	Name	City	State
Australia	Investigational Site Number : 0363002	Carlton	Victoria
Australia	Investigational Site Number : 0363003	East Melbourne	Victoria
Australia	Investigational Site Number : 0363001	Parkville	Victoria
Bulgaria	Investigational Site Number : 1002004	Pleven
Bulgaria	Investigational Site Number : 1002002	Sofia
Bulgaria	Investigational Site Number : 1002003	Sofia
Bulgaria	Investigational Site Number : 1002005	Sofia
Bulgaria	Investigational Site Number : 1002006	Sofia
Canada	Investigational Site Number : 1240014	Barrie	Ontario
Canada	Investigational Site Number : 1240020	Hamilton	Ontario
Canada	Investigational Site Number : 1241106	Markham	Ontario
Canada	Investigational Site Number : 1240018	Newmarket	Ontario
Canada	Investigational Site Number : 1241108	Niagara Falls	Ontario
Canada	Investigational Site Number : 1240026	Toronto	Ontario
Canada	Investigational Site Number : 1241107	Waterloo	Ontario
Canada	Investigational Site Number : 1241101	Windsor	Ontario
Czechia	Investigational Site Number : 2032108	Brno
Czechia	Investigational Site Number : 2032106	Kutna Hora
Czechia	Investigational Site Number : 2032104	Ostrava
Czechia	Investigational Site Number : 2032102	Praha 10
Czechia	Investigational Site Number : 2032101	Praha 2
Czechia	Investigational Site Number : 2032103	Praha 3
Germany	Investigational Site Number : 2762203	Berlin
Germany	Investigational Site Number : 2762202	Blankenfelde-Mahlow
Germany	Investigational Site Number : 2762207	Gera
Germany	Investigational Site Number : 2762208	Kiel
Germany	Investigational Site Number : 2762201	Münster
Hungary	Investigational Site Number : 3482303	Debrecen
Hungary	Investigational Site Number : 3482305	Gyula
Hungary	Investigational Site Number : 3482306	Szolnok
Japan	Investigational Site Number : 3923112	Adachi-Ku	Tokyo
Japan	Investigational Site Number : 3923115	Chuo-Ku	Tokyo
Japan	Investigational Site Number : 3923104	Edogawa-Ku	Tokyo
Japan	Investigational Site Number : 3923109	Habikino-Shi
Japan	Investigational Site Number : 3923108	Kagoshima-Shi	Kagoshima
Japan	Investigational Site Number : 3923102	Kyoto-Shi	Kyoto
Japan	Investigational Site Number : 3923107	Minato-Ku	Tokyo
Japan	Investigational Site Number : 3923114	Obihiro-Shi	Hokkaido
Japan	Investigational Site Number : 3923110	Sakai-shi	Osaka
Japan	Investigational Site Number : 3923101	Sapporo	Hokkaido
Japan	Investigational Site Number : 3923105	Setagaya-Ku	Tokyo
Japan	Investigational Site Number : 3923106	Shimotsuga-gun	Tochigi
Japan	Investigational Site Number : 3923113	Yokohama-Shi	Kanagawa
Poland	Investigational Site Number : 6162419	Bialystok	Podlaskie
Poland	Investigational Site Number : 6162402	Gdansk	Pomorskie
Poland	Investigational Site Number : 6162403	Gdansk	Pomorskie
Poland	Investigational Site Number : 6162404	Gdynia	Pomorskie
Poland	Investigational Site Number : 6162405	Katowice	Slaskie
Poland	Investigational Site Number : 6162406	Krakow	Malopolskie
Poland	Investigational Site Number : 6162408	Krakow
Poland	Investigational Site Number : 6162409	Krakow
Poland	Investigational Site Number : 6162407	Kraków	Malopolskie
Poland	Investigational Site Number : 6162415	Lódz	Lódzkie
Poland	Investigational Site Number : 6162416	Lódz	Lódzkie
Poland	Investigational Site Number : 6162401	Rzeszow	Podkarpackie
Poland	Investigational Site Number : 6162410	Szczecin	Zachodniopomorskie
Poland	Investigational Site Number : 6162411	Warszawa	Mazowieckie
Poland	Investigational Site Number : 6162412	Warszawa	Mazowieckie
Poland	Investigational Site Number : 6162413	Warszawa	Mazowieckie
Poland	Investigational Site Number : 6162414	Wroclaw	Dolnoslaskie
Poland	Investigational Site Number : 6162417	Wroclaw	Dolnoslaskie
Poland	Investigational Site Number : 6162418	Wroclaw	Dolnoslaskie
Spain	Investigational Site Number : 7242505	Alicante
Spain	Investigational Site Number : 7242501	Córdoba
Spain	Investigational Site Number : 7242503	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7242504	Pontevedra	Galicia [Galicia]
Taiwan	Investigational Site Number : 1583201	Kaohsiung Hsien,
Taiwan	Investigational Site Number : 1583202	Taichung
Taiwan	Investigational Site Number : 1583203	Tao Yuan County
United Kingdom	Investigational Site Number : 8262601	London	London, City Of
United Kingdom	Investigational Site Number : 8262603	London	London, City Of
United States	CONTINENTAL CLINICAL RESEARCH Site Number : 8401011	Baltimore	Maryland
United States	Revival Research Corporation - Michigan - ClinEdge - PPDS Site Number : 8401012	Doral	Florida
United States	Florida International Research Center Site Number : 8401091	Miami	Florida
United States	Medical Research Center of Miami II, Inc Site Number : 8401019	Miami	Florida
United States	Sanchez Clinical Research, Inc Site Number : 8401095	Miami	Florida
United States	International Clinical Research-Tennessee LLC Site Number : 8401008	Murfreesboro	Tennessee
United States	Aeroallergy Research Laboratories Of Savannah Inc Site Number : 8401004	Savannah	Georgia
United States	Alliance Clinical Research - Tampa Site Number : 8401013	Tampa	Florida
United States	Vital Prospects Clinical Research Institute, P.C. Site Number : 8401005	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Japan,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants who experienced treatment-emergent adverse event (TEAE)	Percentage of participants who experienced TEAE	Baseline to Week 120
Secondary	Percentage of participants who experienced treatment-emergent SAEs	Percentage of participants who experienced treatment-emergent SAEs	Baseline to Week 120
Secondary	Percentage of participants who experienced treatment-emergent adverse events of special interest (AESI)	Percentage of participants who experienced treatment-emergent AESI	Baseline to Week 120
Secondary	Absolute change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24	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.	DRI17366 Baseline to Week 104
Secondary	Percent change from DRI17366 baseline in EASI score at each LTS17367 visit in participants entering the study from DRI17366 Week 24	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.	DRI17366 Baseline to Week 104
Secondary	Proportion of participants with EASI75/EASI90/EASI100 from DRI17366 baseline at each LTS17367 visit in participants entering the study from DRI17366 Week 24	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.; EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline.	DRI17366 Baseline to Week 104
Secondary	Proportion of participants with a response of validated investigator global assessment (vIGA-AD) 0 or 1 at each LTS17367 visit in participants entering the study from DRI17366 Week 24	The IGA 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.	Baseline to Week 104
Secondary	Absolute change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study	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.	Baseline to Week 104
Secondary	Percent change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study	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.	Baseline to Week 104
Secondary	Proportion of participants with EASI50/ EASI75/ EASI90/ EASI100 at pre-specified timepoints in all participants entering the studyPercent change from parent study baseline in EASI score at pre-specified timepoints in all participants entering the study	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.; 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.	Baseline to Week 104
Secondary	Time to first EASI75/EASI90/EASI100 in those participants who had not achieved it by the time of LTS17367 entry in all participants entering the study	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.; EASI75: >= 75% reduction in score from baseline; EASI90: >= 90% reduction in score from baseline; EASI100: >= 100% reduction in score from baseline.	Baseline to Week 104
Secondary	Time to first remission after LTS17367 enrolment (achieving vIGA-AD 0/1) in those participants who had not achieved vIGA-AD 0/1 by the time of LTS17367 entry in all participants entering the study	The IGA 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.	Baseline to Week 104
Secondary	Proportion of participants with vIGA-AD score 0/1 at each visit in all participants entering the study	The IGA 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.	Baseline to Week 104
Secondary	Proportion of participants with low disease activity state (e.g., vIGA-AD =2) at each visit in all participants entering the study	The IGA 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.	Baseline to Week 104
Secondary	Proportion of participants requiring rescue treatment at each visit: all treatments in all participants entering the study	Proportion of participants requiring rescue treatment at each visit: all treatments in all participants entering the study.	Baseline to Week 120
Secondary	Proportion of participants requiring rescue treatment at each visit: topical treatments in all participants entering the study	Proportion of participants requiring rescue treatment at each visit: topical treatments in all participants entering the study.	Baseline to Week 120
Secondary	Proportion of participants requiring rescue treatment at each visit: systematic treatments in all participants entering the study	Proportion of participants requiring rescue treatment at each visit: systematic treatments in all participants entering the study.	Baseline to Week 120
Secondary	Number of days on topical medication (per patient-year) in all participants entering the study	Number of days on topical medication (per patient-year) in all participants entering the study.	Baseline to Week 120
Secondary	Change from parent study baseline to prespecified time points through the end of the study: atopic dermatitis control tool (ADCT) in all participants entering the study	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.	Baseline to Week 104
Secondary	Change from parent study baseline to prespecified time points through the end of the study: dermatology life quality index (DLQI) in all participants entering the study	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.	Baseline to Week 104
Secondary	Change from parent study baseline to prespecified time points through the end of the study: patient oriented eczema measure (POEM) in all participants entering the study	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.	Baseline to Week 104
Secondary	Serum amlitelimab concentration assessed at prespecified time points through the end of the study	Serum amlitelimab concentration assessed at prespecified time points through the end of the study.	Baseline to Week 104
Secondary	Anti-amlitelimab antibody titre in participants with positive response	Anti-amlitelimab antibody titre in participants with positive response.	Baseline to Week 120
Secondary	Number of participants with positive anti-drug antibody response	Number of participants with positive anti-drug antibody response.	Baseline to Week 120