CTRI/2023/12/060418RecruitingPhase 2
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
Sanofi India Limited (SIL)8 sites in 1 country901 target enrollmentStarted: May 14, 2024Last updated:
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 901
- Locations
- 8
- Primary Endpoint
- - To characterize the safety of long-term treatment with amlitelimab monotherapy administered by sub-cutaneous (SC) injection in participants with moderate-to-severe AD
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Masking
- None
Eligibility Criteria
- Ages
- 18.00 Year(s) to 99.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •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.
- •Is a woman of nonchildbearing potential (WONCBP) as defined in Appendix 4 (Section 10.4): Contraceptive and barrier guidance;.
- •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.
- •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.
Exclusion Criteria
- •Skin co-morbidity that would adversely affect the ability to undertake AD assessments (eg, psoriasis, tinea corporis, lupus erythematosus) as per investigator’s judgment E
- •Known history of or suspected significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
- •Any malignancies or history of malignancies prior to baseline (except for in situ cervical carcinoma that has been excised and cured, or non-melanoma skin cancer that has been excised and cured for more than 3 years prior to baseline).
- •History of solid organ or stem cell transplant.
- •Any pre-planned major elective surgery known about at baseline that in the opinion of the investigator would necessitate that IMP be permanently discontinued or require more than three doses to be missed.
- •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.
- •Any medical or psychiatric condition which, in the opinion of the Investigator may present an unreasonable risk to the study participants as a result of his/her participation in this clinical study, may make participant’s participation unreliable, or may interfere with study assessments.
- •Any active or chronic infection including helminthic infection requiring systemic treatment within 2 weeks prior to baseline (1 week in the event of superficial skin infections); or any active infection (including confirmed Covid-19 infection at screening or baseline) which as per Investigator’s opinion inhibit the participant’s participation in the study.
- •Treatment with live (attenuated) vaccines within 12 weeks prior to baseline; failure to complete non-live immunizations required by local regulation (eg, vaccination for COVID-19) at least 14 days prior to baseline E
- •Concurrent participation in any other clinical study, including non-interventional studies.
- •Participants positive for human immunodeficiency virus; participants with any of the following results at Screening (Visit 1): Positive (or indeterminate) HBsAg, or positive IgM HBcAb, or positive total HBcAb confirmed by positive HBV DNA; positive HCVAb confirmed by positive HCV RNA.
- •Participants with active TB, latent TB, a history of incompletely treated TB, suspected extrapulmonary TB 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.
- •Note: TB testing is mandatory to rule out active/latent TB and should be performed and assessed according to local guidelines.
- •Participants with a confirmed positive IGRA test are excluded from the study unless all of the following conditions are met: i) 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, AND ii) have obtained consultation with a specialist to rule out or treat active TB infection, AND iii) for whom review and approval from Sponsor have been granted are eligible.
- •If an indeterminate IGRA result is found at the first evaluable test, a retest should be performed as soon as possible.
- •If the second evaluable test is negative study participant is not excluded.
- •If the second evaluable test is either indeterminate or positive, study participant is excluded.
- •In the event of test cancelation, a retest should be performed as soon as possible, and the cancelation will not account as an evaluable test result.
- •In the Investigator’s opinion, any clinically significant laboratory results from the clinical chemistry, haematology or urinalysis tests at the screening visit or specifically any of the following laboratory abnormalities at Screening (Visit 1): • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times upper limit of normal range (ULN) • Serum total bilirubin > 1.5xULN (participants with Gilbert’s syndrome can be included with total bilirubin > 1.5xULN as long as direct bilirubin is < 1.5xULN) • Hemoglobin < 10g/dL • Neutrophils < 1.5×109 /L • Platelets < 100 x ×109 /L (< 100,000/mm3 ) • Creatinine > 150µmol/L E
- •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.
- •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
- •Any country-related specific regulation that would prevent the participant from entering the study (refer Section 10.8).
- •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
- •Any anticipated situation during study implementation/course that may raise ethics considerations.
- •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.
Outcomes
Primary Outcomes
- To characterize the safety of long-term treatment with amlitelimab monotherapy administered by sub-cutaneous (SC) injection in participants with moderate-to-severe AD
Time Frame: From baseline to Week 52
- Percentage of participants who experienced Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From baseline to Week 52
- Percentage of participants who experienced Treatment-Emergent Serious Adverse Events (TESAEs)
Time Frame: From baseline to Week 52
Secondary Outcomes
- - 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)
Investigators
Study Sites (8)
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