2022-502653-34-01招募中4 期
A phase 3b, interventional, adaptive, clinical trial to evaluate the efficacy and safety of tralokinumab 300 mg every second week monotherapy compared with placebo in subjects with moderate-to-severe atopic hand eczema who are candidates for systemic therapy (ADHAND)
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 191
- 试验地点
- 51
- 主要终点
- IGA-AHEa score of 0 (clear) or 1 (almost clear) at Week 16.
研究概览
简要总结
To evaluate the efficacy of tralokinumab on severity and extent of atopic hand eczema compared with placebo in treatment of subjects with moderate-to-severe atopic hand eczema
研究设计
- 分配方式
- Randomized
- 主要目的
- Treatment period
- 盲法
- Double (Monitor, Subject, Investigator)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Signed and dated informed consent as described in Appendix 1, Section 10.1.3 has been obtained prior to any protocol related procedures.
- •A HESD itch score (weekly average) score of ≥4 at baseline. The baseline weekly average will be calculated from daily assessments of itch severity during the 7 days immediately preceding the baseline visit (Day -7 to Day -1). A minimum of 4 scores out of the 7 days is required to calculate the baseline average score. - For subjects who do not have at least 4 daily scores reported during the 7 days immediately preceding the planned randomization date, randomization should be postponed until this requirement is met.
- •Subjects who have a documented recent history (within 12 months before the screening visit) of inadequate response to treatment of AHE with topical prescription medications or for whom topical treatments are otherwise medically inadvisable (e.g., due to important side effects or safety risks). - Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to an IGA-AHE score of ≤2) despite treatment with a daily regimen of TCS of US class ≤4 (medium to very/ultra-high potency) and Europe class ≥3 (potent to very potent) (with or without TCI as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super potent TCS), whichever is shorter. - Subjects with documented systemic treatment for AHE in the past year are also considered as inadequate responders to topical treatments and are potentially eligible for enrollment after appropriate wash-out. - Important side effects or safety risks are those that outweigh the potential treatment benefits and include intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the investigator or by the subject’s treating physician.
- •A WOCBP* must use a highly effective** form of birth control throughout the trial and for at least 16 weeks (5 half-lives) after last administration of IMP. * A WOCBP is defined as a female subject aged ≥12 years who, at the discretion of the investigator, is deemed to be of reproductive potential. A woman is defined as not being of childbearing potential if she is postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening), or surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). **A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), sexual abstinence (when this is in line with the preferred and usual life style of the subject and not just being without a current partner), same-sex partner, or vasectomized partner (given that the subject is monogamous).
- •Age 18 years or above at screening.
- •Willingness to comply with the clinical trial protocol. Type of subject and disease characteristics
- •Diagnosis of AD as defined by the Hanifin and Rajka (44) criteria for AD (Appendix 5, Section 10.5).
- •History of AD for at least 12 months prior to screening
- •Presence of AHE that has persisted for more than 3 months or returned twice or more within the last 12 months (7), with avoidance of any known and relevant irritants and allergens.
- •Disease severity graded as moderate-to-severe at screening and baseline according to IGA-AHE (i.e., an IGA-AHE score of 3 or 4).
- •AD involvement of at least one body location other than the hands and wrists at screening.
- •Subjects must adhere to standard non-medicated skin care including avoidance of known and relevant allergens and irritants from screening through end of treatment (Week 32).
排除标准
- •Subjects must not enter the trial if they have active subtypes of hand eczema other than AHE that are considered to be the predominant cause of the current hand eczema includinga: - Active irritant contact dermatitis where a relevant exposure to irritants is considered as the predominant cause of the current hand eczema. - Active allergic contact dermatitis where a relevant exposure to allergens is considered as the predominant cause of the current hand eczema; this includes subjects with a positive patch test reactionb within 3 years prior to screening that is deemed to be clinically relevant as the predominant cause of the current hand eczema. - Active protein contact dermatitis/contact urticaria where a relevant exposure to proteins is considered as the predominant cause of the current hand eczema. - Active hyperkeratotic hand eczema considered as the predominant cause of the current hand eczema. - Active vesicular hand eczema (pompholyx) considered as the predominant cause of the current hand eczema. a. Further guidance on classification of hand eczema is provided in Appendix 6 (Section 10.6). b. Patch testing is not a requirement.
- •History of cancer: - Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained. - Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
- •History of any known primary immunodeficiency disorder including a positive HIV test at screening.
- •Current or recent chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator.
- •Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could: - Affect the safety of the subject throughout the trial. - Influence the findings of the trial or their interpretations. - Impede the subject’s ability to complete the entire duration of trial.
- •Any clinically significant abnormal findings in physical examination, vital signs, hematology, or clinical chemistry during the screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the trial, or may influence the results of the trial, or the subject’s ability to complete the entire duration of the trial.
- •Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), or hepatitis B core antibody (anti-HBc), or hepatitis C virus antibody serology at screening. Subjects with positive anti-HBs are eligible provided that they have a negative HBsAg and negative anti-HBc (blood pattern in vaccinated subjects).
- •Women who are pregnant or lactating.
- •Treatment with the following medications within 28 days prior to baseline: - Systemic immunosuppressive/immunomodulating drugs (e.g., methotrexate, cyclosporin A, azathioprine, mycophenolate mofetil, JAK inhibitors, retinoids [e.g., alitretinoin]). - Systemic corticosteroid use (excludes topical, inhaled, ophthalmic, or intranasal delivery).
- •Use of tanning beds, phototherapy (e.g., UVB, UVA1, PUVA), or Grenz ray therapy on the hands or wrists within 28 days prior to baseline or use of bleach baths on the hands or wrists within 7 days prior to baseline.
- •Treatment with the following medications within 7 days prior to baseline: - TCS*. - TCI*. - Topical PDE-4 inhibitors. - Topical JAK inhibitors. * Mild-to-moderate TCS (US class ≥4 or Europe class ≤3) or TCI related to AD treatment on other areas of the body than the hands and wrists are allowed as long as it does not interfere with the trial (i.e., the subjects must use disposable gloves when applying treatment or have it applied by someone other than self).
- •Active dermatologic condition on any part of the body, including the hands and wrists, that may confound the diagnosis of AD or AHE, or that would interfere with the assessment of treatment (such as seborrheic dermatitis, active skin infection, scabies, cutaneous T cell lymphoma, or psoriasis).
- •Use of cutaneously applied antibiotics or other transdermal or cutaneously applied therapy on the hands or wrists (except for the use of subject’s own emollients) within 7 days prior to baseline.
- •Receipt of any biological therapy (including immunoglobulin and anti-IgE): - Any cell-depleting agents including but not limited to rituximab: within 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is the longest. - Dupilumaba: within 3 months prior to baseline. - Tralokinumabb: within 3 months prior to baseline. - Other biologics: within 3 months prior to baseline or 5 half-lives, whichever is the longest. a. Subjects who have discontinued treatment with dupilumab due to lack of efficacy must not enter the trial. b. Subjects who have discontinued treatment with tralokinumab due to lack of efficacy or due to a safety concern and for whom continued tralokinumab treatment may present an unreasonable safety risk, must not enter the trial.
- •Subjects who have received treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within the last 28 days prior to baseline or 5 half-lives, whichever is the longest.
- •Receipt of live (attenuated) vaccines within 28 days prior to baseline and during the trial, including the safety follow-up period. - Receipt of inactive/killed vaccinations (e.g., inactive influenza and inactive COVID 19 vaccines) is allowed.
- •Receipt of blood products within 28 days prior to screening.
- •Current participation in any other interventional clinical trial.
- •Previously randomized in this clinical trial.
- •Planned in-patient surgery or hospitalization during the trial period.
- •Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.
- •Subjects who are legally institutionalised.
- •Clinically significant infection on the hands or wrists, e.g., impetiginized hand eczema.
- •History of a clinically significant infection within 28 days prior to baseline which, in the opinion of the investigator or sponsor’s medical expert, may compromise the safety of the subject in the trial, interfere with the evaluation of the IMP, or reduce the subject’s ability to participate in the trial. Clinically significant infections are defined as: - a systemic infection. - a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.
- •A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
- •Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care.
- •Known or suspected hypersensitivity to any component(s) of the IMPs.
- •History of anaphylaxis following any biological therapy.
- •History of immune complex disease.
结局指标
主要结局
IGA-AHEa score of 0 (clear) or 1 (almost clear) at Week 16.
IGA-AHEa score of 0 (clear) or 1 (almost clear) at Week 16.
次要结局
- Having a decrease in HECSIb of at least 75% (HECSI-75) from baseline to Week 16
- Having a decrease in HECSI of at least 50% (HECSI-50) from baseline to Week 16.
- Having a decrease in HECSI of at least 90% (HECSI-90) from baseline to Week 16.
- Percentage change in HECSI score from baseline to Week 16
- Having a ≥2-point reduction in IGA-AHE score from baseline to Week 16.
研究者
LEO Pharma Clinical Trials mailbox
Scientific
LEO PHARMA A/S
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