Pharmacokinetics, Safety and Efficacy of Nemolizumab in Participants Aged 6 to 23 Months With Moderate-to Severe Atopic Dermatitis

Official title

A Multicenter, Open-Label, Single-Group Clinical Study to Assess the Pharmacokinetics, Safety and Efficacy of Nemolizumab in Pediatric Subjects (Aged 6 to 23 Months) With Moderate-to-Severe Atopic Dermatitis Not Adequately Controlled With Topical Therapy

Overview

The primary objective of the study is to assess the pharmacokinetics (PK) and safety of nemolizumab in pediatric participants (aged 6-23 months) with moderate-to-severe atopic dermatitis (AD) who are not adequately controlled with topical treatments.

Detailed description

Participants will be screened up to 4 weeks prior to the Baseline visit. At Baseline/Day 1, all participants will receive a loading dose of nemolizumab high dose administered subcutaneously (SC), followed by nemolizumab low dose SC every 4 weeks (Q4W) during the 52-week treatment period, with the final study treatment administered at Week 48.

After completion of the 52-week treatment period, participants will enter an 8-week safety follow-up period through Week 60. Participants who prematurely discontinue the study before the Week 48 visit will be followed for 12 weeks after their last administration of study treatment.

Interventions

• Drug Nemolizumab
  A lyophilized powder for solution for SC injection.

Primary outcome measures

• Observed Nemolizumab Serum Concentrations [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Total Body Clearance For Extravascular Administration (Cl/F) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Apparent Volume of Distribution for Extravascular Administration (Vd/F) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• First-Order Absorption Rate Constant (ka) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Area Under the Concentration-Time Curve Across Time (From Zero to Infinity) (AUCinf)) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Terminal Half-Life (t1/2) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Trough Serum Concentration at Each Specified Time Point (predicted Ctrough) of Nemolizumab [Time frame: Predose at Weeks 4, 16, 32 and 52]
• Number of Participants with Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), Adverse Events Leading to Discontinuation and Serious Adverse Events (SAEs) [Time frame: Baseline up to Week 60]

Eligibility criteria

Inclusion criteria

• Participants greater than and equal to (>=) 6 to less than (<) 24 months of age at the screening visit.
• Diagnosis of AD according to the American Academy of Dermatology Consensus Criteria at the time of the screening visit.
• Eczema Area and Severity Index (EASI) score >= 16 at both screening and baseline visits.
• Investigator's Global Assessment (IGA) score >= 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both screening and baseline visits.
• AD involvement >= 10 percent (%) of body surface area (BSA) at both screening and baseline visits. (Note: BSA to be derived from the SCORing Atopic Dermatitis (SCORAD).)
• Weekly average of worst scratch/itch Numeric Rating Scale (WSI-NRS) score of at least 4 at both screening and baseline visits as assessed by the parent(s)/caregiver:

• Screening WSI-NRS score will be determined by a single WSI-NRS assessment (score ranging from 0 to 10) for the 24-hour period immediately preceding the screening visit.
• Baseline WSI-NRS score will be determined based on the average of daily WSI-NRS scores (score ranging from 0 to 10) during the 7 days immediately preceding baseline (rounding not permitted). A minimum of 4 daily scores out of the 7 days immediately preceding baseline is required for this calculation. For participants who do not have at least 4 daily scores reported during the 7 days immediately preceding the planned enrollment date, enrollment should be postponed until this requirement is met, without exceeding the maximum screening duration of 4 weeks.
• Documented history by a physician and/or investigator of inadequate response to existing topical AD medications or use of systemic therapies for control of the disease (within 6 months before the screening visit).
• Participant's parent(s)/caregiver willing and able to comply with all time commitments and procedural requirements of the clinical study protocol.
• Participant's parent(s)/caregiver understand and sign a parental Informed Consent Form (ICF) before any study-related procedures are performed.
• Participant's parent(s)/caregiver agree to apply a moisturizer daily from the screening visit and liberally as needed throughout the study; if applying a prescribed topical corticosteroid (TCS) prior to study enrollment, agree to continue at the same stable dose from screening and throughout the study as determined appropriate by the investigator.

Exclusion criteria

• Body weight < 5 Kilograms (kg).
• Child in Care: a child placed under the control or protection of an agency, organization, institution, or entity by courts or government authorities under applicable law or regulation.
• Cutaneous infection within 1 week before the baseline visit or any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit. Participants may be rescreened once the infection has resolved.Note: A participant with mild, localized superficial infection may be included based on investigator discretion.
• Having received any of the following treatments within the specified timeframe before the baseline visit:

Coal tar products - 2 weeks Topical Janus kinase (JAK) inhibitor - 2 weeks Topical phosphodiesterase-4 (PDE-4) inhibitor - 2 weeks Medium and higher potency TCS - 2 weeks Topical calcineurin inhibitor (TCI) - 2 weeks Topical medications with occlusive dressings (e.g., wet wraps) - 2 weeks Systemic corticosteroids (inhaled and intraocular permitted) - 4 weeks Immunosuppressive or immunomodulatory drugs (e.g., cyclosporine A, oral tacrolimus, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil, JAK inhibitors) - 4 weeks or 5 half-lives (whichever is longer) Biologics and biosimilars (e.g., etanercept, adalimumab, infliximab, omalizumab) - 8 weeks or 5 half-lives (whichever is longer) Dupilumab - 10 weeks Live (attenuated) vaccine - 4 weeks Alternative medicine for AD (e.g., traditional Chinese medicine) - 2 weeks For participants with planned live (attenuated) vaccination during the study, consultation with a pediatrician will determine whether vaccination should be postponed until study completion or administered before study start without compromising health. Inactivated vaccines (e.g., diphtheria, tetanus, pertussis (DPT), hepatitis A, hepatitis B, inactivated polio vaccine (IPV), haemophilus influenzae type B, meningococcal, pneumococcal, influenza) are permitted.

• Participants who, after a full 16-week treatment course with dupilumab, experienced worsening of AD or failed to achieve minimal improvement (e.g., <= 10% reduction in EASI or no reduction in IGA).
• History of lymphoproliferative disease or malignancy of any organ system before the screening visit.
• History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) or any study treatment excipients.
• Known or suspected primary immunodeficiency.
• History of, or current confounding skin condition (e.g., Netherton syndrome, psoriasis, contact dermatitis, dermatitis herpetiformis, erythroderma, ichthyosis, scabies) that may interfere with study assessments.
• Any medical condition (e.g., serious cardiac, hepatic, pulmonary \[including uncontrolled asthma\], or hematologic disease) or clinically relevant laboratory abnormality during screening that may place the participant at significant risk or interfere with study assessments (e.g., poor venous access or needle phobia). Note: Laboratory tests with abnormal results may be repeated once during screening; the last value will determine eligibility.

Uncontrolled asthma defined as one or more of the following:

• Asthma exacerbation requiring hospitalization since birth (<=12 months of age) or within the preceding 12 months (>12 months of age)
• Daytime asthma symptoms >2 times per week during the preceding 3 months
• Nighttime awakenings >2 times per month during the preceding 3 months
• Asthma exacerbation requiring oral corticosteroids or additional Short-Acting
• Beta-Agonist (SABA) inhalers >2 times per week during the preceding 3 months

• Planned or expected major surgical procedure during the clinical study.
• Planned or anticipated use of prohibited medications during the study.
• Currently participating or participated in another clinical study of an investigational drug or device within the past 8 weeks (or 5 half-lives, whichever is longer) before the screening visit, or currently in an exclusion period from a previous clinical study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07660835 · SPR.118130 · 2025-525027-27-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗