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)
- Trial ID
- 2022-502653-34-01
- Protocol
- LP0162-2328
- Sponsor
- Leo Pharma A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the **efficacy** of tralokinumab on the severity and extent of moderate-to-severe atopic hand eczema compared with placebo. This is clinically relevant as it aims to determine the potential of tralokinumab as a therapeutic option for patients who are candidates for systemic therapy, potentially improving disease management and patient outcomes.
Secondary objectives include:
- Evaluating the efficacy of tralokinumab on additional parameters such as itch, pain, sleep, and health-related quality of life compared with placebo.
- Assessing the safety and tolerability of tralokinumab in the same patient population.
Participants
The clinical trial involves a total of **211 participants** diagnosed with **atopic dermatitis** and moderate-to-severe atopic hand eczema. The study population includes both male and female subjects aged 18 years and above, with no vulnerable populations selected. Participants were chosen based on specific inclusion criteria, including a documented history of inadequate response to topical treatments for atopic hand eczema and a willingness to comply with the clinical trial protocol. The general health status of participants is characterized by the presence of moderate-to-severe disease severity, as assessed by the Investigator's Global Assessment for Atopic Hand Eczema (IGA-AHE). Participants are required to adhere to standard non-medicated skin care and avoid known allergens and irritants throughout the trial duration. The trial does not impose specific lifestyle considerations such as diet or physical activity, but participants must avoid any known and relevant irritants and allergens. The sponsor has not provided additional information regarding the selection process or other lifestyle factors.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **tralokinumab** 300 mg administered every second week as a monotherapy compared to a placebo in subjects with moderate-to-severe atopic hand eczema who are candidates for systemic therapy. This is a phase 3b, interventional, adaptive trial with a randomized, double-blind, and controlled design. The trial is expected to commence recruitment on December 4, 2023, and conclude by March 22, 2027, with a maximum treatment period of 40 weeks.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease severity, and previous treatment response. The primary inclusion criteria include a documented history of inadequate response to topical treatments and a baseline itch score of ≥4. The trial will include follow-up visits at regular intervals to monitor the participants' response to the treatment and any adverse effects. The primary endpoint is achieving an Investigator's Global Assessment for Atopic Hand Eczema (IGA-AHE) score of 0 (clear) or 1 (almost clear) by Week 16. Secondary endpoints include various degrees of improvement in the Hand Eczema Severity Index (HECSI) score from baseline to Week 16.
The expected length of participant involvement is approximately 32 weeks, with conditions for early termination including non-compliance with the protocol, adverse events, or withdrawal of consent. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to evaluate the overall efficacy and safety of the treatment. Participants are required to adhere to standard non-medicated skin care and avoid known allergens and irritants throughout the trial duration.
Treatment
The clinical trial involves the administration of **tralokinumab**, an investigational medicinal product, to evaluate its efficacy and safety in subjects with moderate-to-severe atopic hand eczema. **Tralokinumab** is provided as a **solution for injection in a pre-filled syringe**. The active substance, **tralokinumab**, is a protein of non-human origin. The pharmaceutical form is a single-use, disposable, needle-based injection system with a passive needle safety guard, designed to deliver a fixed dose of 300 mg via **subcutaneous use**. The maximum daily dose is 600 mg, with a total treatment period of up to 40 weeks. The product is manufactured in compliance with the Marketing Authorization Application (MAA) for Adtralza® and is subject to specific drug product specifications and batch release data to ensure quality and efficacy. The shelf life of the clinical trial material is 60 months, reflecting careful handling and storage conditions.
The trial also includes a **placebo** comparator, which is presented in a pre-filled syringe containing the same excipients in identical amounts as the investigational medicinal product. The placebo is used to assess the efficacy of **tralokinumab** by providing a baseline for comparison. The placebo does not contain any active substance and is administered in the same manner as the investigational product, ensuring blinding and consistency in the trial design. The use of a placebo is critical in determining the true therapeutic effect of **tralokinumab** in the treatment of atopic hand eczema.
Efficacy
The efficacy of **tralokinumab** in the treatment of moderate-to-severe atopic hand eczema will be assessed through a series of primary and secondary endpoints. The primary endpoint is the achievement of an Investigator's Global Assessment for Atopic Hand Eczema (IGA-AHE) score of 0 (clear) or 1 (almost clear) at Week 16. Secondary endpoints include a decrease in Hand Eczema Severity Index (HECSI) scores by at least 75% (HECSI-75), 50% (HECSI-50), and 90% (HECSI-90) from baseline to Week 16, as well as the percentage change in HECSI score from baseline to Week 16. Additionally, a reduction of at least 2 points in the IGA-AHE score from baseline to Week 16 will be evaluated.
These efficacy parameters will be measured at specific timepoints, with the primary and secondary endpoints being assessed at Week 16. The assessments will involve validated scales such as the IGA-AHE and HECSI, which are standard tools for evaluating the severity and extent of atopic hand eczema. The data collected will be analyzed to determine the efficacy of tralokinumab compared to placebo in achieving the desired clinical outcomes in subjects with moderate-to-severe atopic hand eczema.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent as described in Appendix 1, Section 10.1.3 has been obtained prior to any protocol related procedures.
- 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).
- 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).
Exclusion Criteria
- 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.
- 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).
- 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.
- 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).
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 04 Dec 2023 | 15 |
 Czechia | Not Recruiting | 04 Dec 2023 | 30 |
 France | Not Recruiting | 04 Dec 2023 | 24 |
 Germany | Not Recruiting | 04 Dec 2023 | 30 |
 The Netherlands | Not Recruiting | 04 Dec 2023 | — |
 Poland | Not Recruiting | 04 Dec 2023 | 34 |
 Portugal | Not Recruiting | 04 Dec 2023 | 17 |
 Spain | Not Recruiting | 04 Dec 2023 | 17 |
 Sweden | Not Recruiting | 04 Dec 2023 | 14 |
| Netherlands | — | — | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TRALOKINUMAB | Test | — | SUBCUTANEOUS USE | 600 | 40 | SUB189645 |
The placebo presentation is a pre-filled syringe containing the same excipients in the same amounts as the IMP. | Placebo | N/A | — | — | — | N/A |