Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis With Inadequate Response to or for Whom Cyclosporine A is Not Medically Advisable

NCT05056779 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: RD.06.SPR.2015912021-002166-40
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to investigate the efficacy of nemolizumab administered in combination with topical background therapy (topical corticosteroids \[TCS\] with or without topical calcineurin inhibitors \[TCI\]) in adult participants with moderate-to-severe atopic dermatitis (AD) who are not adequately controlled with or are not advised to use oral cyclosporine A (CsA) for medical reasons. The secondary objective is to investigate the safety of nemolizumab in adult participants with moderate-to-severe AD who are not adequately controlled with or are not advised to use oral CsA for medical reasons. The study will be carried out in up to 70 different locations across Europe.

Conditions

Moderate-to-severe Atopic Dermatitis

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants with Eczema Area and Severity Index-75 (EASI-75) (≥ 75% Improvement in EASI from Baseline) at Week 16

  EASI assesses severity and extent of AD signs through a composite score of erythema, induration/population, excoriation, and lichenification. The severity will be assessed on a scale of 0 (absent) to 3 (severe) for each of the 4 body areas: head/neck, trunk, upper limbs, and lower limbs, with half points allowed. The EASI score can range from 0 to 72 with higher scores representing greater severity of atopic dermatitis.

  Week 16

• Proportion of Participants with an Improvement of Peak Pruritus Numeric Rating Scale (PP NRS) ≥ 4 at Week 16

  Pruritus NRS is a scale that will be used by the participants to report the intensity of their pruritus (itch) during the last 24 hours. For maximum itch intensity: the scores are provided on a scale of 0 to 10, with 0 being 'no itch' and 10 being 'worst itch imaginable'. Higher scores indicate worse outcome.

  Week 16

Secondary Outcomes (26)

• Percent Change from Baseline in EASI at Each Visit Through Week 16

  Baseline through week 16

• Proportion of Participants with at Least 50%, 75%, or 90% Improvement from Baseline in Eczema Area and Severity Index (EASI-50, EASI-75, and EASI-90) at Each Visit Through Week 16

  Baseline through week 16

• Percent Change From Baseline in Peak Pruritus Numeric Rating Scale (PP NRS) at Each Visit Through Week 16

  Baseline through week 16

• Proportion of Participants with an Improvement of Peak Pruritus Numeric Rating Scale (PP NRS) ≥ 4 at Week 1, Week 2, and Each Visit Through Week 16

  From Week 1 to Week 16

• Proportion of Participants with Peak Pruritus Numeric Rating Scale (PP NRS) < 2 at each Visit Through Week 16

  Baseline through week 16

Study Arms (2)

Nemolizumab

EXPERIMENTAL

Drug: Nemolizumab

Placebo

EXPERIMENTAL

Drug: CD14152 placebo

Interventions

Nemolizumab DRUG

Participants will receive loading dose of 60 milligram (2×30 mg) subcutaneous (SC) injection of nemolizumab at baseline. Thereafter 30 mg nemolizumab will be administered via single SC injection once in 4 week (Q4W) up to week 12.

Also known as: CD14152

Nemolizumab

CD14152 placebo DRUG

Participants will receive loading dose of 60 mg (2×30 mg) SC injection of placebo at baseline. Thereafter 30 mg placebo will be administered via single SC injection Q4W up to week 12.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic AD for at least 2 years before the screening visit and confirmed according to American Academy of Dermatology Consensus at the time of the screening visit.
• EASI score ≥ 20 at both the screening and baseline visits. Participant with an EASI score of 18-19 at the screening visit only may be reevaluated once within 48 hours.
• IGA score ≥ 3 (based on the IGA scale ranging from 0 to 4, in which 3 is moderate and 4 is severe) at both the screening and baseline visits.
• AD involvement ≥ 10% of BSA at both the screening and baseline visits.
• Documented history by a physician (within 6 months before the screening visit) of inadequate response to topical medications or use of systemic therapies for control of the disease.
• Agree to apply a moisturizer throughout the study from the screening visit; agree to apply an authorized TCS, with or without TCI, from the screening visit and throughout the study as determined appropriate by the investigator.
• Documented history of one of the following, where CsA treatment should not be continued/restarted or participant is not currently a candidate for CsA treatment:
• Inadequate response to CsA with previous exposure (defined as flare of AD during CsA tapering from a maximum of 6 weeks of high dose \[5 mg/kg/day\] to maintenance dose \[2 to 3 mg/kg/day\] or a flare after a minimum of 3 months on maintenance dose). Flare is defined as increase in signs and/or symptoms leading to escalation of therapy (ie, increase in dose, switch to a higher-potency topical corticosteroids \[TCS\] or start of another systemic nonsteroidal immunosuppressive drug), or
• Previous requirement for CsA at doses \> 5 mg/kg/day, or duration beyond those specified in the prescribing information (\> 1 year)
• Intolerance and/or unacceptable toxicity (eg, elevated creatinine, elevated liver function tests, uncontrolled hypertension, paresthesia, headache, nausea, hypertrichosis) with previous CsA exposure
• CsA is medically inadvisable due to medical contraindication, use of prohibited medications, risk of AEs (eg, serious infection) or toxicity (eg, renal or liver damage), or hypersensitivity to CsA or excipients, in the opinion of the investigator
• Acceptable documentation includes patient records with information on CsA prescription and treatment outcome, other prohibitive medications/medical history, or written documentation of the conversation with the participant's treating physician, if different than the investigator, as applicable.

You may not qualify if:

• Body weight \< 30 kg.
• One or more of the following criteria at screening or baseline:
• Exacerbation of asthma requiring hospitalization in the preceding 12 months.
• Asthma that has not been well controlled (i.e, symptoms occurring on \> 2 days per week, nighttime awakenings 2 or more times per week, or some interference with normal activities) during the preceding 3 months.
• Asthma Control Test (ACT) ≤ 19 (only for subjects with a history of asthma).
• Peak expiratory flow (PEF) \< 80% of the predicted value.
• Current medical history of chronic obstructive pulmonary disease and/or chronic bronchitis.
• Positive serology results (hepatitis B surface antigen \[HBsAg\] or hepatitis B core antibody \[HBcAb\], hepatitis C \[HCV\] antibody with positive HCV RNA, or human immunodeficiency virus \[HIV\] antibody) at the screening visit.
• Presence of confounding skin conditions that may interfere with study assessments.
• Planned or expected major surgical procedure during the clinical study.

Sponsors & Collaborators

• Galderma R&D: lead

MeSH Terms

Interventions

nemolizumab

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: September 27, 2021
• Study Start: January 1, 2023
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: September 21, 2023

Record last verified: 2021-09