Open label, long-term study evaluating safety and efficacy of subcutaneous amlitelimab in participants aged 12 years and older with moderate to severe atopic dermatitis
An Open-Label multinational, multicenter study to evaluate the long-term safety, tolerability, and efficacy of subcutaneous amlitelimab in participants aged 12 years and older with moderate to severe atopic dermatitis
Trial Acronym
ATLANTIS
Secondary IDs if Any
Secondary ID
Identifier
2022-502188-39-00
Other
LTS17789, Version number: 1, dated 31Oct2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Godhuli Chatterjee
Designation
Medical Advisor
Affiliation
Sanofi India Limited (SIL)
Address
Sanofi House, C.T.S. No. 117/B, L&T Business Park, Saki
Vihar Road, Powai
Sanofi House, C.T.S. No. 117/B, L&T Business Park, Saki
Vihar Road, Powai
Mumbai MAHARASHTRA 400 072 India
Phone
917045402595
Fax
Email
Vibhawari.Waghanna@sanofi.com
Source of Monetary or Material Support
Sanofi India Limited, Sanofi House, C.T.S No.117b, L& T Business park, Saki Vihar Road, Powai, Mumbai -400072
Primary Sponsor
Name
Sanofi India Limited (SIL)
Address
Sanofi House, C.T.S. No. 117/B, L&T Business Park, Saki
Vihar Road, Powai, Mumbai, Maharashtra, 400 072, India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Brazil Canada Chile China Czech Republic Denmark France Germany India Italy Japan Mexico Netherlands Poland Republic of Korea South Africa Spain Taiwan United Kingdom United States of America
Clinical research department, 4th & 5thTH Floor, Star Plus Commercial Complex, Bytco 1 Nashik MAHARASHTRA
9373901829
suneel.vartak@gmail.com
Dr Saswati Halder
Calcutta School of tropical medicine
Department of Dermatology, 108, Chittaranjan Avenue, Kolkata, West Bengal 700073 Kolkata WEST BENGAL
9434427717
saswatihalder32@gmail.com
Dr Sowmya C S
KIMS Hospital
Kempegowda Institute of Medical Sciences (KIMS) Hospital and Research centre, B Block, 2nd floor, Department of dermatology, K.R Road,V.V Puram Bangalore KARNATAKA
560004
sowmya.cs17@gmail.com
Dr Abin Abraham Itty
Lakeshore Hospital and Research Centre ltd, Kochi
Maradu, Nettoor P.O., Kochi, 682040 Kerala Ernakulam KERALA
125 mg/mL amlitelimab solution in a PFS to deliver 250 mg of amlitelimab in a 2 mL injection 250 mg (125 mg/mL)
62.5 mg/mL amlitelimab solution in a PFS to deliver 125 mg of amlitelimab in a 2 mL injection 125 mg (62.5 mg/mL)
- Participant must be at least 12 years of age inclusive, at the time of signing the informed consent.
- Participants must have AD as defined by the American Academy of Dermatology Consensus Criteria (45) for 1 year or longer at baseline.
- The sponsor may be allowed to close some sub-groups based on the ongoing recruitment to guarantee a diverse population.
.AD in patient with intrinsic disease
.AD in patients with skin of color
.AD patients with co-morbid asthma
.AD patients with concurrent hand eczema
.AD patients who have an incomplete response or intolerance of approved prior biologics therapies
- Participants who stopped biologic treatment due to non-response, partial response, loss of efficacy (e.g., failure to achieve or maintain remission [IGA 0, clear skin to 2, mild disease]) must have been previously treated with biologic (at labelled dose level) for at least 4 months, as confirmed by investigator judgment.
- Participants who stopped biologic treatment due to intolerance or AEs to the drug may enter the study with no required prior length of biologic treatment.
- Participant must have documented history within 6 months prior to screening visit, of either inadequate response or inadvisability of topical treatments
- EASI of 16 or higher at baseline visit.
- vIGA-AD of 3 or 4 at baseline visit (on the 0 to 4 vIGA-AD scale, vIGA-AD 3 and 4 for moderate and severe respectively).
- AD involvement of 10% or more of BSA at baseline visit.
- Weekly average of daily PP-NRS of ≥ 4 at baseline visit. This calculation shall include all reported values in the 7 days immediately preceding the baseline visit. A minimum of 4 scores is required to allow calculation of the average. For participants who have not entered at least 4 daily PP-NRS during the 7 days immediately preceding the planned enrollment date, enrollment should be postponed until this requirement is met, but without exceeding the 28-day maximum duration for screening.
- Must demonstrate understanding and appropriate use of the e-diary and participant questionnaires, including collection of PP-NRS prior to baseline visit.
- Able and willing to comply with requested study visits and procedures.
- Body weight must be greater than or equal to 25 kg
- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) Male participants Male participants are eligible to participate if they agree to the
following during the study intervention period and for at least 5 months after the last administration of study intervention: • Refrain from donating sperm • Plus either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR - Must agree to use contraception/barrier as detailed below:
- A male condom; the participant should also be advised of the benefit for a female partner to use a highly effective method of contraception (as will be described in Appendix 4 (Section 10.4): Contraceptive and barrier guidance) as a condom may break or leak when having sexual intercourse with a WOCBP who is not currently pregnant
- b) Female participants A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 4 (Section 10.4): Contraceptive and barrier guidance;
- OR - Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of <1%, as will be described in Appendix 4 (Section 10.4): Contraceptive
and barrier requirements, during the study intervention period (to be effective before starting the intervention) and for at least 5 months after the last administration of study intervention.
- A WOCBP must have a negative highly sensitive pregnancy test (serum as required by local regulations) within 28 days before the first administration of study intervention, as will be described in Section 8.3.5
- Capable of giving a signed informed assent and/or 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. The signed ICF must always be present at the time of inclusion
E 15. In the Investigator’s opinion, any significant abnormality on 12-lead ECG at the screening visit that could be suggestive of an unstable or underlying cardio-vascular condition that could preclude the participant’s participation in the study
E 16. History of hypersensitivity or allergy to any of the excipients or IMP or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Known or suspected hypersensitivity to amlitelimab or excipients used in the presentation of amlitelimab or in preparation for administration.
E 17. Individuals accommodated in an institution because of regulatory or legal order; participants who are legally institutionalized; persons who have been placed in an institution on the basis of an official court order
E 18. Any country-related specific regulation that would prevent the participant from entering the study (refer Section 10.8).
E 19. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
E 20. Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with section 1.61 of the ICH-GCP Ordinance E6)
E 21. Any anticipated situation during study implementation/course that may raise ethics considerations.
E 22. History (within last 2 years prior to baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator.
E 23: Presence of either of the following at Screening or Baseline Visits: a) active suicidal ideation or suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to Question 1, 2, or 3, of the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Questions b) presence of active suicidal ideation with an intent and/or plan or any lifetime history of suicidal ideation with an intent and/or plan as indicated by a positive response ("Yes") to Question 4 or 5 of C-SSRS Suicidal Ideation Questions c) presence of active suicidal behavior or any lifetime history of suicidal behavior including suicide attempt (including actual attempt, interrupted attempt, or aborted attempt), preparatory acts for suicide attempt, or non-suicidal self-injurious behavior as indicated by a positive response ("Yes") to any Suicide Behavior Questions of C-SSRS
d) assessment by the Investigator through participant interview and review of medical history of high risk of suicidal behavior. Note: C-SSRS assessment will be implemented only in newly screened participants after the amended protocol 02 upon local approval.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
- To characterize the safety of long-term treatment with amlitelimab monotherapy administered by sub-cutaneous (SC) injection in participants with moderate-to-severe AD
- Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)
- Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)
- Additional characterization of the safety of long-term treatment with amlitelimab monotherapy administered by SC injection in participants with moderate-to-severe AD
- To characterize the efficacy of treatment with amlitelimab monotherapy administered by SC injection in participants with moderate-to-severe AD
- To characterize the effect of amlitelimab on measures of Patient-Reported Outcomes (PROs) & quality of life (QoL)
- Percentage of participants who experienced Treatment-Emergent Adverse Events of Special Interest (AESI)
- Percentage of participants with Potentially Clinically Significant Abnormalities (PCSA) for vital signs & clinical laboratory assessments , & electrocardiogram (ECG)
Total Sample Size="901" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
his is a
multinational, multicenter, single arm, open-label, long-term study to evaluate
the safety and efficacy of amlitelimab in adult participants with
moderate-to-severe AD. The study duration will be of 180 weeks, including a
screening period of up to 2 to 4 weeks (28 days, and with a minimum of 14
days), open label treatment period of at least 160 weeks (approximately 3 years),
and a post-treatment follow up period of up to 20 weeks after the last dose
administration (last IMP administration at Week 156).
Up to 571
participants with moderate to severe AD will be included in the study and will
receive a loading dose of amlitelimab 500 mg subcutaneously at Day 1, followed
by amlitelimab 250 mg subcutaneously Q4W.
To ensure
sufficient numbers for each sub population are recruited adjustments to site
recruitment may be made throughout the recruitment period. The study will include:
• A screening
period of no more than 28 days (and with a minimum of 14 days) to ensure all
eligibility requirements for study entry are confirmed and IMP available on
site.
• Open-label
treatment period: no shorter than 160 weeks but could continue above this
period as long as the overall benefit/risk is in favor of continued development
of amlitelimab in AD and is aligned with Sponsor decision to continue clinical
development in AD
• A
post-treatment safety follow-up period of 20 weeks after the last dose of IMP.
Visits during the treatment period will be at Weeks 0, 2 and 4 then once every
4 weeks until Week 52, then once every 12 weeks thereafter until the end of
treatment. Between planned visits, if deemed necessary unscheduled remote or
clinic visits could be performed.
After Week 52 participants are allowed to
perform self-injections at home according to the schedule of dosing.
Alternatively, if needed, and based on the investigator’s judgement, home
visits (eg, home nurses, etc) or on-site IMP administration visits can be
performed for IMP administration. In case of home injections, a caregiver/LAR
may also administer IMP