Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis

Phase 3

Recruiting

• Conditions: Eczema; Atopic Dermatitis
• Interventions: Biological: Lebrikizumab

• Registration Number: NCT05990725
• Lead Sponsor: Almirall, S.A.

Brief Summary

The main purpose of this study is to evaluate the effectiveness of 24 weeks of lebrikizumab in improving disease severity, signs, and symptoms in adults and adolescents with moderate-to-severe atopic dermatitis (AD).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-07
• Study First Submitted QC: 2023-08-07
• Study First Posted: 2023-08-14
• Study Start: 2023-11-20
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-24
• Last Update Posted: 2024-04-25
• Primary Completion: 2025-05-01
• Study Completion: 2025-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

• Adults and adolescents (aged >=12 to less than [<] 18 years at the time of informed consent form (ICF)/informed assent form (IAF) signature and weighing >=40 kg) who are candidates for systemic AD therapy.
• Chronic AD that has been present for >=1 year before the Screening visit.
• EASI score >=12 at the Day 1/Baseline Visit.
• IGA score >=3 (moderate) (scale of 0 [clear] to 4 [severe]) at the Baseline visit.
• >=10% BSA of AD involvement at the Day 1/Baseline visit.
• History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.
• Completed eDiary entries for pruritus and sleep-loss for a minimum of 4 of 7 days before Day 1/Baseline.
• Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
• For women of childbearing potential: agree to remain abstinent (refrain from heterosexual intercourse) or to use a highly effective contraceptive method during the treatment period and for at least 4 weeks or 1 menstrual period after the last dose of lebrikizumab.
• Participant must provide signed ICF. Adolescent participants must also provide separate informed assent to enroll in the study and sign and date either a separate IAF or the ICF signed by the parent/legal guardian (as appropriate based on local regulations and requirements).

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Exclusion Criteria

• Prior treatment at any time with tralokinumab, lebrikizumab, or an oral JAK inhibitor.

• Intention to use any concomitant medication or therapy that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication.

• History of anaphylaxis as defined by the Sampson criteria.

• Uncontrolled chronic disease that might require bursts of oral corticosteroids, example, co-morbid severe uncontrolled asthma (defined by an Asthma Control Questionnaire-5 score >=1.5 or a history of >=2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalisation for >24 hours).

• Have had any of the following types of infection within 3 months of Screening or develop any of these infections before Day 1/Baseline:

  1. Serious (requiring hospitalisation, and/or IV or equivalent oral antibiotic treatment, as per the Investigator's opinion);
  2. Opportunistic
  3. Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or longer);
  4. Recurring (including, but not limited to herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis).

• Known current or chronic infection with hepatitis B virus.

• Known current infection with hepatitis C virus (that is, positive for hepatitis C RNA).

• Known liver cirrhosis and/or chronic hepatitis of any aetiology.

• Diagnosed active endoparasitic infections or at high risk of these infections.

• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (example, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgement.

• History of human immunodeficiency virus (HIV) infection or known positive HIV serology.

• In the Investigator's opinion, any clinically significant laboratory test results from the chemistry or haematology tests obtained at the Screening visit.

• Presence of skin comorbidities that may interfere with study assessments.

• History of malignancy, including mycosis fungoides, within 5 years before the Screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin with no evidence of recurrence in the past 12 weeks.

• Severe concomitant illness(es) that in the Investigator's judgement would adversely affect the participation in the study. Any other medical or psychological condition that in the opinion of the Investigator may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant because of his/her participation in this clinical trial, may make participation unreliable, or may interfere with study assessments.

• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lebrikizumab	Lebrikizumab	Participants will receive lebrikizumab 250 milligrams (mg) subcutaneous (SC) injection, once every two weeks (Q2W) on Day 1 for up to Week 16. A loading dose of lebrikizumab 500 mg (2 injections) SC will be administered on Day 1 and at Week 2, further followed by lebrikizumab 250 mg (1 injection), SC, once every four weeks (Q4W) after Week 16 for up to Week 24.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Score Less Than or Equal to (<=) 7 at Week 24	Baseline, Week 24	The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee 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. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%).

Secondary Outcome Measures

Name	Time	Method
Mean EASI Score	Baseline up to Week 24	The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease.
Percentage of Participants Achieving SCORAD 50, 75, and 90	Baseline up to Week 24	The SCORAD is a validated measure of the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition. SCORAD 50 is defined as 50% reduction in SCORAD from baseline. SCORAD 75 is defined as 75% reduction in SCORAD from baseline. SCORAD 90 is defined as 90% reduction in SCORAD from baseline.
Percentage Change From Baseline in Pruritus NRS score	Baseline up to Week 24	The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable. Assessments will be recorded by the participant using an eDiary.
Percentage of Participants with an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction Greater Than or Equal to (>=2) Points	Baseline up to Week 24	The IGA is an instrument used to globally rate the severity of the participants's AD. It is based on a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe), and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting (minimal, palpable induration and significant induration).
Percent Change From Baseline in Body Surface Area (BSA)	Baseline up to Week 24	The BSA assessment estimates the extent of disease or skin involvement with respect to AD and is expressed as a percentage of total body surface. BSA will be determined by the Investigator or designee using the participant palm = 1% BSA rule. The participant's palm is measured from the wrist to the proximal interphalangeal and thumb.
Percentage Change From Baseline in Scoring Atopic Dermatitis (SCORAD)	Baseline up to Week 24	SCORAD is a validated clinical tool for assessing the extent and intensity of AD. There are 3 components: surface involvement, intensity part and subjective assessment. Surface involvement is assessed as proportion of involved surface area segment by segment by applying the rule of 9s. Intensity part of the SCORAD consists of 6 items: erythema, oedema, oozing/crusting, excoriation, lichenification, and dryness. Each item is graded as follows: none (0), mild (1), moderate (2), or severe (3) (for a maximum of 18 total points). Subjective assessment of itch and of sleeplessness is recorded for each symptom using a VAS, where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness), for maximum possible score of 20. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition.
Percentage of Participants Achieving EASI Score <=7, <=5, and <=3	Baseline up to Week 24	The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. The severity of erythema, induration/papulation, excoriation, and lichenification will be assessed by the Investigator or trained designee 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. In addition, the extent of AD involvement in each of the 4 body areas will be assessed as a percentage by body area of head/neck, trunk, upper limbs, and lower limbs, and converted to a score of 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%).
Percentage Change From Baseline in EASI Total Score	Baseline up to Week 24	The EASI is used to assess the severity, extent of AD clinical signs and percentage (%) of BSA affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score is based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranges from 0 to 72, where higher scores indicate greater severity of AD.
Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS)	Baseline up to Week 24	mTLSS combines an evaluation of hand eczema lesions severity including 6 key signs (erythema, desquamation, lichenification/hyperkeratosis, vesiculae, oedema, fissures) and the intensity of pruritus and pain. The seven features of AD of the hand (erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, fissures, pruritus/pain) form the composite scale of mTLSS' strength and each one of them scores from 0 (mild) to 3 (severe). The scores is summed, extending from a base estimation of 0 (no signs or symptoms) to the most extreme of 21 (more serious disease).
Percentage of Participants Achieving DLQI 0-1	Baseline up to Week 24	The DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. A high score is indicative of a poor QoL. DLQI scores indicates 0-1 (no effect on patient's life), 2-5 (small effect on patient's life), 6-10 (moderate effect on patient's life), 11-20 (very large effect on patient's life), 21-30 (extremely large effect on patient's life).
Percentage of Participants With DLQI Greater Than (>) 5 at Baseline Achieving DLQI <=5	Baseline up to Week 24	DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. High score is indicative of a poor QoL.
Percentage of Participants With a Face IGA Score of 0 or 1 and a Reduction >=2 Points	Baseline up to Week 24	The IGA is an instrument used to globally rate the severity of the participants's AD. It is based on a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe), and a score is selected using descriptors that best describe the overall appearance of the lesions at a given time point. The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting (minimal, palpable induration and significant induration).
Change From Baseline in Dermatology Life Quality Index (DLQI)/Children Dermatology Life Quality Index cDLQI	Baseline up to Week 24	DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. High score is indicative of a poor QoL. CDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. CDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced.
Percentage of Participants Achieving cDLQI 0-1	Baseline up to Week 24	cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced.
Participant and Investigator-Reported Satisfaction Questionnaire	Baseline up to Week 24	The Participant-Reported Satisfaction Questionnaire asks, "How satisfied are you with this treatment's ability to treat your skin condition?". The response options range from 1 (not satisfied) to 5 (completely satisfied). Higher score representing higher satisfaction on that domain.
Percentage of Participants Achieving EASI 50, 75, and 90 Reduction From Baseline	Baseline up to Week 24	The EASI is used to assess the severity and extent of AD; it is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and or extensive disease. EASI 50 is defined as 50% reduction from baseline in the EASI score. EASI 75 is defined as 75% reduction from baseline in the EASI score. EASI 90 is defined as 90% reduction from baseline in the EASI score.
Percentage of Participants with Pruritus Numerical Rating Scale (NRS) >=4 at Baseline Achieving Pruritus NRS score <=4	Baseline up to Week 24	The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable. Assessments will be recorded by the participant using an electronic Dairy (eDiary).
Percentage of Participants With DLQI >=4 at Baseline Achieving >=4-Point Improvement in DLQI	Baseline up to Week 24	DLQI is a 10-item validated questionnaire completed by the participant or caregiver used to assess the impact of skin disease on the participant's QoL during the previous week. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment. Each question is scored from 0=not at all, 1=a little, 2=a lot, and 3=very much, giving a total score ranging from 0 to 30. High score is indicative of a poor QoL.
Percentage of Participants With cDLQI >5 at Baseline Achieving cDLQI <=5	Baseline up to Week 24	cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced.
Percentage of Participants With Patient-Oriented Eczema Measure (POEM) >=4 at Baseline Achieving >=4-Point Improvement in POEM	Baseline up to Week 24	The POEM is a 7-item, validated questionnaire completed by the participant (and, if applicable, with help of parents/caregiver if required) to assess disease symptoms. Participants are asked to respond to questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping. All answers carry equal weight, with a total possible score ranging from 0 to 28 (answers scored as: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; every day = 4. A high score is indicative of a poor quality of life. POEM responses will be captured weekly using an eDiary.
Itch Controlled Days Questionnaire Using PRO	Baseline up to Week 24	The Itch Controlled Days questionnaire is a validated PRO composed of a set of questions that describe several parameters related to the course of pruritus over the course of the day. Specifically, the scale assesses itch presence and severity, the need to scratch, and sleep quality and sleep disturbances due to itching, rated on scales of 0 to 10. The questionnaire also assesses itch duration and temporal patterns associated with itch over a 24-hour period.
Percentage of Participants With Pruritus NRS >=4 at Baseline Achieving >=4-Point Improvement in Pruritus NRS	Baseline up to Week 24	The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours, with 0 indicating "No itch," and 10 indicating "Worst itch imaginable. Assessments will be recorded by the participant using an eDiary.
Percentage of Participants With a Sleep-Loss Scale of >=2 Points at Baseline Who Achieve at least 2-point Reduction Using PRO	Baseline up to Week 24	Sleep loss will be assessed by all participants using a patient-related outcome (PRO) instrument. Participants (and if applicable, with help of parents/caregiver if required) will rate their sleep on a 5-point Likert scale (with scores ranging from 0 \[not at all\] to 4 \[unable to sleep at all\]). Assessments will be recorded by the participant using an eDiary.The baseline Sleep-Loss Scale score will be determined based on the average of daily Sleep-Loss Scale scores during the 7 days immediately before the Day 1 or Baseline visit.
Change From Baseline in Sleep-Loss Scale Using PRO	Baseline up to Week 24	Sleep loss will be assessed by all participants using a PRO instrument. Participants (and if applicable, with help of parents/caregiver if required) will rate their sleep on a 5-point Likert scale (with scores ranging from 0 \[not at all\] to 4 \[unable to sleep at all\]). Assessments will be recorded by the participant using an eDiary.The baseline Sleep-Loss Scale score will be determined based on the average of daily Sleep-Loss Scale scores during the 7 days immediately before the Day 1 or Baseline visit.
Participant and Investigator Completed Treatment Satisfaction Questionnaires Version 9 (TSQM-9)	Baseline up to Week 24	The TSQM-9 is a conceptually and psychometrically valid PRO instrument that assesses four key dimensions of treatment satisfaction: effectiveness, side effects, convenience, and global satisfaction, enabling comparisons across medication types and diseases. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.
Patient Global Assessment of Disease Status (PGADS)	Baseline up to Week 24	Patient Global Assessment of Disease Status (PGADS) measures static disease severity. Participants are asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" and rate their overall well-being based on a 5-point Likert scale which ranged from 0 (extremely poor) to 100 (excellent). Higher score indicates better outcome.
Percentage of Participants With cDLQI >=6 at Baseline Achieving >=6-Point Improvement in cDLQI	Baseline up to Week 24	cDLQI is validated from adolescents younger than age of 16 years, which is based on a set of 10 questions different from those of the DLQI. The answers to the questions are generally scored on a 4-point scale from 0=not at all or question unanswered, 1=only a little, 2=quite a lot, 3=very much. cDLQI is calculated by summing the score of each question resulting in 0 to 30. Higher the score, the more impairment of the child's life is experienced.
Percentage Change From Baseline in POEM	Baseline up to Week 24	The POEM is a 7-item, validated questionnaire completed by the participant (and, if applicable, with help of parents/caregiver if required) to assess disease symptoms. Participants are asked to respond to questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping. All answers carry equal weight, with a total possible score ranging from 0 to 28 (answers scored as: No days = 0; 1-2 days = 1; 3-4 days = 2; 5-6 days = 3; every day = 4. A high score is indicative of a poor quality of life. POEM responses will be captured weekly using an eDiary.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, AEs Leading to Study Treatment Discontinuation, and Adverse Events of Special Interest (AESIs)	Baseline up to follow-up (Week 28)	An AE is defined as any untoward medical occurrence in a clinical trial participant, regardless of the administration of the IMP and its causal relationship to it. An AE can therefore be any unfavourable/unintended medical occurrence during the participation in the trial, including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, ECG abnormality, or an abnormal finding in the physical examination. An SAE is an AE, which falls into any of the following categories: death, is life-threatening, requires in-patient hospitalisation or prolongs existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect, or any other medically important event that may jeopardise the participant or may require intervention to prevent one of the other above outcomes. The following treatment-emergent AEs are being designated as AESIs: conjunctivitis, herpes simplex or zoster infection and parasitic infections.

Trial Locations

Locations (33)

Site 3; 🇩🇪 Hamburg, Germany

Site 23; 🇩🇪 Heidelberg, Germany

Site 8; 🇩🇪 Hamburg, Germany

Site 34; 🇩🇪 Augsburg, Germany

Site 27; 🇩🇪 Dresden, Germany

Site 37; 🇩🇪 Frankfurt, Germany

Site 5; 🇩🇪 Göttingen, Germany

Site 1; 🇩🇪 Kiel, Germany

Site 10; 🇩🇪 Lübeck, Germany

Site 26; 🇩🇪 Mainz, Germany

Site 36; 🇩🇪 Marburg, Germany

Site 6; 🇩🇪 Mannheim, Germany

Site 13; 🇩🇪 München, Germany

Site 17; 🇩🇪 München, Germany

Site 33; 🇩🇪 München, Germany

Site 4; 🇩🇪 Münster, Germany

Site 12; 🇩🇪 Oberhausen, Germany

Site 30; 🇩🇪 Regensburg, Germany

Site 7; 🇩🇪 Rostock, Germany

Site 18; 🇩🇪 Tübingen, Germany

Site 14; 🇬🇧 York, United Kingdom

Site 38; 🇬🇧 Leeds, United Kingdom

Site 35; 🇳🇱 Bergen Op Zoom, Netherlands

Site 41; 🇳🇱 Utrecht, Netherlands

Site 29; 🇩🇪 Bonn, Germany

Site 9; 🇩🇪 Berlin, Germany

Site 28; 🇩🇪 Düsseldorf, Germany

Site 11; 🇩🇪 Erlangen, Germany

Site 32; 🇩🇪 Freiburg, Germany

Site 15; 🇩🇪 Hamburg, Germany

Site 19; 🇩🇪 Langenau, Germany

Site 22; 🇩🇪 Oldenburg, Germany

Site 2; 🇩🇪 Potsdam, Germany