Efficacy and Safety of Daxdilimab in Adults with Moderate-to-Severe Primary Discoid Lupus Erythematosus: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2023-509746-35-00
Protocol: HZNP-DAX-202
Sponsor: Horizon Therapeutics Ireland Designated Activity Company

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Chronic cutaneous lupus erythematosus

Objectives

The primary objective of this study is to evaluate the effect of **daxdilimab** compared with placebo in reducing active disease activity at Week 24 in participants with moderate-to-severe primary discoid lupus erythematosus (DLE). This is clinically relevant as DLE is a chronic dermatological condition that can lead to significant morbidity, and effective treatments are needed to manage disease activity and improve patient outcomes.

Secondary objectives include:

Evaluating the effect of daxdilimab compared with placebo in reducing DLE disease activity at Week 24 in participants with primary DLE.
Assessing the effect of daxdilimab compared with placebo on disease activity and damage in participants with primary DLE.
Characterizing the pharmacokinetics and immunogenicity of daxdilimab in participants with primary DLE.
Evaluating the safety and tolerability of daxdilimab in participants with primary DLE.

Participants

The clinical trial involves a total of **36 participants** diagnosed with **Primary Discoid Lupus Erythematosus** (DLE). The study population includes both male and female adults aged between 18 and 75 years. Participants were selected based on their diagnosis of DLE for at least six months prior to screening, confirmed by either a biopsy or a clinical feature score on the DLE Classification Criteria scale. The trial includes individuals with currently active discoid lupus, as confirmed by digital photography and a CLASI-A score of 8 or higher. Participants are required to have treatment-refractory DLE, defined as active disease despite current or historical treatment with systemic therapies, or a documented history of intolerance to antimalarials and/or immunosuppressive medications. The trial population is characterized by a stable dosage of any ongoing therapies, such as antimalarials, methotrexate, mycophenolate, azathioprine, or corticosteroids, prior to screening and throughout the trial. Both male and female participants must adhere to specific contraceptive guidelines to prevent pregnancy during the study. The trial also includes a vulnerable population, ensuring that all participants have provided written informed consent and comply with local vaccination standards.

Plans and Procedures

The clinical trial is a **Phase 2**, multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of **daxdilimab** subcutaneous injection in reducing disease activity in adult participants with moderate-to-severe primary discoid lupus erythematosus. The trial aims to assess the effect of daxdilimab compared with placebo over a period of 24 weeks, with the primary endpoint being the mean change in the CLASI-A score from baseline to Week 24. Secondary endpoints include the proportion of participants achieving a score of 0 or 1 on the CLA-IGA scale at Week 24, a ≥ 50% reduction in CLASI-A score from baseline, and various safety and pharmacokinetic measures.

The trial is expected to last until December 2026, with participant recruitment having commenced in May 2023. Participants will be involved in the study for a maximum of 48 weeks, which includes the screening, treatment, and follow-up periods. The study visits are structured as follows: an initial screening visit to confirm eligibility, followed by randomization and baseline assessments. Subsequent visits will occur at regular intervals to monitor safety, efficacy, and pharmacokinetics, culminating in an end-of-study visit at Week 24. Participants will be required to maintain stable dosages of any concurrent therapies throughout the trial.

Inclusion criteria stipulate that participants must be adults aged 18 to 75 years with a confirmed diagnosis of discoid lupus erythematosus for at least six months prior to screening. They must have active disease despite current or historical treatment with systemic therapies. Exclusion criteria are not specified in the provided data. Conditions that may lead to early termination from the study include non-compliance with the treatment protocol, adverse events, or withdrawal of consent. The trial is not categorized as low intervention, and it is not an orphan drug study.

Treatment

The clinical trial involves the administration of **Daxdilimab**, an investigational medication, to evaluate its efficacy and safety in reducing disease activity in adult participants with moderate-to-severe primary discoid lupus erythematosus. **Daxdilimab** is provided in the form of an injection, with the active substance being a protein of other origin. The pharmaceutical form is specifically designed for **subcutaneous use**. The maximum daily dose is 300 mg, and the total dose does not exceed 300 mg over a treatment period of up to 48 weeks. The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in this double-blind, placebo-controlled trial. The placebo consists of normal saline, provided as a solution for injection. The placebo is administered in a manner identical to the experimental treatment to maintain the study's blinding and integrity. The use of a placebo allows for a rigorous assessment of **Daxdilimab**'s therapeutic effects by providing a baseline for comparison. Participant compliance with the placebo administration is also monitored to ensure the reliability of the trial results.

Efficacy

The efficacy of the investigational product, **daxdilimab**, will be assessed in a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The primary endpoint for evaluating efficacy is the mean change in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score from Baseline (Day 1) to Week 24. This score is a validated measure used to assess disease activity in patients with discoid lupus erythematosus (DLE).

Secondary efficacy endpoints include the proportion of participants achieving a score of 0 or 1 on the Cutaneous Lupus Erythematosus Disease Area and Severity Index Investigator's Global Assessment (CLA-IGA) scale at Week 24, which is a 5-point Likert scale ranging from 0 to 4. Additionally, the proportion of participants achieving a ≥ 50% reduction in CLASI-A score from Baseline at Week 24 will be evaluated. Another secondary endpoint is the mean change in the Severity of Alopecia Tool for Discoid Lupus Erythematosus (SADDLE) from Baseline to Week 24.

Pharmacokinetics and immunogenicity assessments will include measuring the serum concentration of daxdilimab over time and the incidence of anti-drug antibodies (ADA) directed against daxdilimab. These assessments will provide insights into the drug's behavior in the body and potential immune responses. The schedule for these assessments will align with the trial's protocol, ensuring systematic data collection and analysis at specified timepoints throughout the study duration.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the United States) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
Adult men or women ≥ 18 and ≤ 75 years of age.
A diagnosis of DLE for ≥ 6 months prior to Screening supported by a history of a. A biopsy or b. a clinical feature score of ≥ 7 on the DLE Classification Criteria (DLECC) scale if a biopsy is not available.
Currently active discoid lupus with all the following: a. Digital photography adjudicated with central reading to confirm a currently active discoid disease lesion. b. CLASI-A score ≥ 8 related to discoid lesions at Baseline.
Treatment refractory DLE defined as active disease despite current or historical treatment with a systemic treatment including, but not limited to antimalarial, methotrexate, mycophenolate, azathioprine, dapsone, corticosteroid, thalidomide, or lenalidomide, OR documented history of intolerance to antimalarials and/or immunosuppressive medications.
Participants with active disease who currently are on any of the following therapies must have been on a stable dosage prior to Screening and must remain on a stable dosage through Randomization and for the entire trial as described below: − Antimalarials (eg, hydroxychloroquine, chloroquine, quinacrine) must be at a stable dosage for at least 8 weeks prior to Screening and through Randomization. − Methotrexate ≤ 20 mg/week (oral or SC) at stable dosage and route of administration for at least 4 weeks prior to Screening and through Randomization. − Mycophenolate mofetil ≤ 2 g/day or mycophenolic acid ≤ 1.44 g/day at stable dosage for at least 4 weeks prior to Screening and through Randomization. − Azathioprine must be stable for at least 4 weeks prior to Screening and through Randomization. − Corticosteroid equivalent to prednisone ≤ 10 mg/day at stable dosage for at least 4 weeks prior to Screening and through Randomization. − Topical corticosteroids and calcineurin inhibitors at stable dosage for at least 1 week prior to Screening and through Randomization.
Vaccination status should be up to date per local standards.
Females are eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies: - Is a woman of non-childbearing potential (WONCBP) OR - Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (ie, has a failure rate of < 1%, as described in Appendix 1), during the study intervention period and for at least 6 months after the last dose of IP and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. o A WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1. o Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5 Pregnancy Testing of the Study Protocol. o The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. The Investigator should also evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of IP.
Males are eligible to participate if they agree to the following during the study intervention period and for at least 3 months after the last dose of IP: − Refrain from donating fresh unwashed semen, PLUS either: − Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent, OR − Must agree to use contraception/barrier as detailed below: o Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a WOCBP who is not currently pregnant. Effective methods of contraception are listed in Appendix 1 of the Study Protocol.

cancel

Exclusion Criteria

Individuals involved in the conduct of the trial, their employees, or immediate family members of such individuals.
Participation in another clinical trial with an investigational drug within 4 weeks prior to Randomization or within 5 published half-lives, whichever is longer.
Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of participant safety or trial results.
Weight > 160 kg (352 pounds) at Screening.
History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous mAb or human Ig therapy.
Breastfeeding or pregnant women or women who intend to become pregnant anytime from signing the ICF through 6 months after receiving the last dose of IP.
History of drug or alcohol abuse that, in the opinion of the Investigator, might affect participant safety or compliance with visits, or interfere with other trial assessments.
Major surgery within 8 weeks prior to Screening or elective surgery planned from Screening through end of Treatment Period.
Splenectomy
Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to Screening through Randomization.
History of clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization; arrhythmia requiring active therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities; or presence of clinically significant abnormality on ECG if, in the opinion of the Investigator, it would increase the risk of trial participation.
History of cancer within the past 5 years, except as follows: − Cutaneous basal cell or squamous cell carcinoma treated with curative therapy.
Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection.
Participant who has given > 499 mL of blood or plasma within 56 days of Screening (during a clinical trial or at a blood bank donation) or plans to give blood or plasma during their participation in the trial or up to 6 months after the last IP administration, whichever is longer.
Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis, or plasma exchange within 8 weeks prior to Randomization and for the total duration of the trial participation.
Known history of a primary immunodeficiency or an underlying condition, such as known human immunodeficiency virus (HIV) infection, or a positive result for HIV infection per central laboratory.
At Screening, any of the following per central laboratory tests (may be repeated once within the same screening period to confirm results prior to Randomization): − Aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN) − Alanine aminotransferase (ALT) > 2.5 × ULN − Total bilirubin (TBL) > 1.5 × ULN (unless due to Gilbert’s syndrome) − Neutrophil count < 1500/μL (or < 1.5×109/L) − Platelet count < 135,000/μL (or < 135×109/L) − Hemoglobin < 10 g/dL (or < 100 g/L) − Total lymphocyte count < 800/μL (or < 0.8×109/L) − Antinuclear antibody titer > 1:320
All participants will undergo testing for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) during Screening. − Participants who are HBsAg positive are not eligible for the study. − Participants who are HBsAg negative and HBcAb positive will be reflex tested for hepatitis B surface antibody (HBsAb). If HBsAb is positive, may be enrolled in the study; if HBsAb is negative, the participant is not eligible for the study.
All participants will undergo testing for hepatitis C antibody (HCVAb) during Screening. − Participants who are HCVAb positive will be reflex tested for hepatitis C virus (HCV) RNA and if HCV RNA is positive, the participant is not eligible for the study .
Active tuberculosis (TB), or a positive IFNγ release assay (IGRA) test at Screening, unless documented history of appropriate treatment for active or latent TB. Participants with an indeterminate IGRA test result can repeat the test, but if the repeat test is also indeterminate, they will be excluded.
Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]) at any time prior to Randomization, including, but not limited to, disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the last 2 years), or ophthalmic herpes.
Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to Randomization.
Any of the following within 30 days prior to signing the ICF and through Randomization: − Clinically significant active infection in the opinion of the Investigator, including ongoing, and chronic infection requiring antibiotics or antiviral medication (chronic nail infections are allowed). − Any infection requiring hospitalization or treatment with intravenous anti infectives. − A participant with a documented positive SARS-CoV-2 test may be rescreened at least 2 weeks after a positive test if the participant is asymptomatic or at least 3 weeks after symptomatic COVID-19 illness.
Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 2 years prior to Randomization.
Any acute illness or evidence of clinically significant active infection on Day 1.
Participants who have COVID-19 or other significant infection, or in the judgment of the Investigator, may be at a high risk of COVID-19 or its complications should not be randomized.
NOTE: Other protocol defined Exclusion criteria may apply.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Bulgaria	Not Recruiting	01 May 2023	10
Czechia	Not Recruiting	01 May 2023	2
Denmark	Not Recruiting	01 May 2023	4
France	Not Recruiting	01 May 2023	4
Germany	Not Recruiting	01 May 2023	6
Greece	Not Recruiting	01 May 2023	4
Poland	Not Recruiting	01 May 2023	6