Discoid Lupus Erythematosus MedDRA version: 25.0 Level: LLT Classification code 10013072 Term: Discoid lupus erythematosus System Organ Class: 100000004858
Conditions
Sponsors
Horizon Therapeutics Ireland DAC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible participants must meet/provide all of the following criteria: 1. Written informed consent and any locally required authorization obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. 3. Adult men or women = 18 and = 75 years of age 4. A diagnosis of DLE for = 6 months prior to screening supported by a history of: a. A biopsy and/or b. a clinical feature score of = 7 on the DLE Classification Criteria (DLECC) scale if a biopsy is not available. 5. 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 6. Treatment refractory DLE defined as active disease despite current or historical treatment with a systemic antimalarial, methotrexate, mycophenolate, azathioprine, dapsone, corticosteroid, thalidomide, or lenalidomide, OR documented history of intolerance to antimalarials and/or immunosuppressive medications. 7. 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 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. 8. Women of childbearing potential (WOCBP) (including those with an onset of menopause < 2 years prior to screening, nontherapy-induced amenorrhea for < 12 months prior to screening, or not surgically sterile [absence of fallopian tubes, ovaries and/or uterus]) must: a. Have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1. b. Agree to use 2 approved forms of contraception, one of which is recommended to be hormonal contraceptives, from at least 4 weeks prior to Day 1 until at least 6 months after the last investigational product (IP) administration or the end of the trial, whichever is longer. c. Refrain from egg retrieval and egg donation during the trial and until at least 6 months after the last IP administration. -Note: Highly effective contraceptive methods (with a failure rate < 1% per year), when used consistently and correctly, include hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectable, or implant), some intrauterine devices or intrauterine systems, sexual abstinence, or vasectomized partner(s) (provided his vasectomy was performed = 4 months prior to Screening), tubal ligation or double barrier methods of contraception (eg, male condom with cervical cap, male condom wi
Exclusion criteria
Exclusion criteria: Participants will be ineligible for this trial if they meet any of the following criteria: 1. Individuals involved in the conduct of the trial, their employees, or immediate family members 2. Participation in another clinical trial with an investigational IP within 4wks prior to Randomization or within 5published half-lives, whichever is longer 3. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of participant safety or trial results. 4. Weight >160kg at Screening 5. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a previous mAb or human Ig therapy 6. Breastfeeding/pregnant women/women who intend to become pregnant anytime from signing the ICF through 6months after receiving the last dose of IP 7. 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 8. Major surgery within 8wks prior to Screening or elective surgery planned from Screening through W48 9. Splenectomy 10. Spontaneous or induced abortion, still or live birth, or pregnancy= 4wks prior to Screening through Randomization 11. History of clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6months 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 12. History of cancer within the past 5 years years, except as follows: In situ carcinoma of the cervix treated with apparent success with curative therapy>12months prior to Screening, or Cutaneous basal cell or squamous cell carcinoma treated with curative therapy. 13. Any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection 14. Participant who has given>50 mL of blood or plasma within 30days of Screening or> 499mL of blood or plasma within 56days of Screening or plans to give blood or plasma during their participation in the trial or up to 6months after the last IP administration, whichever is longer. 15. Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis, or plasma exchange within 8wks prior to Randomization and for the total duration of the trial participation. 16. Known history of a primary immunodeficiency or an underlying condition, e.g.HIV infection, or a positive result for HIV infection. 17. At Screening, any of the following per central laboratory tests: -Aspartate aminotransferase>2.5×upper limit of normal (ULN) -Alanine aminotransferase>2.5×ULN -Total bilirubin>1.5×ULN(unless due to Gilbert’s syndrome) -Neutrophil count1:320 18. Confirmed positive test for hepB virus serology defined as: HepB surface antigen, or HepB core antibody 19. Positive test for hepC virus antibody unless documented as having had successful treatment of active hepC infection. 20. Active TB, or a positive IFN? release assay (IGRA) test at Screening, unless documented history of appropriate treatment for active or latent TB. 21. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]) at any t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Efficacy: To evaluate the effect of daxdilimab compared with placebo in reducing active disease activity at Week 24 in participants with primary DLE.;Secondary Objective: Secondary Efficacy: - To evaluate the effect of daxdilimab compared with placebo in reducing DLE disease activity at Week 24 in participants with primary DLE. - To evaluate the effect of daxdilimab compared with placebo in disease activity and damage in participants with primary DLE. Pharmacokinetics and Immunogenicity: To characterize the PK and immunogenicity of daxdilimab in participants with primary DLE. Safety: To evaluate the safety and tolerability of daxdilimab in participants with primary DLE. Exploratory: To evaluate the effect of daxdilimab compared with placebo on other measures of DLE disease activity. Pharmacodynamics: - To characterize the PD of daxdilimab. - To explore potential associations of genetic variations, gene expression, and profiles of cells and proteins in circulation and tissue with daxdilimab. Quality of Life: To evaluate the effect of daxdilimab on the participant’s perceived burden and impact of DLE.;Primary end point(s): Primary Efficacy: Mean change in CLASI-A score from Baseline (Day 1) to Week 24;Timepoint(s) of evaluation of this end point: Baseline (Day 1), W4, W8, W12, W16, W20, W24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy: - Proportion of participants who achieve 0 or 1 on the CLA-IGA scale at Week 24 (5-point Likert scale [0-4]) - Proportion of participants who achieve a = 50% reduction in CLASI-A score from Baseline (Day 1) at Week 24 - To evaluate the effect of daxdilimab compared with placebo in disease activity and damage in participants with primary DLE. - Mean change in the SADDLE from Baseline (Day 1) to Week 24 Pharmacokinetics and Immunogenicity: - Serum concentration of daxdilimab over time - Incidence of ADA directed against daxdilimab over time Safety: - Incidence of TEAEs - Incidence of TESAEs - Incidence of TEAESIs: hypersensitivity reaction, including anaphylaxis, herpes zoster infection, serious (Grade 3 or higher) viral infection/reactivation, opportunistic infection, and malignancy (except non-melanoma skin cancer) Exploratory: - Proportion of participants who achieve a = 2-point decrease on the CLA-IGA scale (5-point Likert scale [0-4]) from Baseline (Day 1) over time - Proportion of participants who achieve 0 or 1 on the CLA-IGA score over time - Change in CLA-IGA score from Baseline (Day 1) over time - Change in individual CLASI-A components from Baseline (Day 1) over time - Mean change in CLASI-D score from Baseline (Day 1) over time - Change in target discoid lesion characteristics (eg, size, dyspigmentation, etc) assessed by digital photography from Baseline over time - Proportion of participants with onset of one or more new discoid lesions (assessed by digital photography) over time - Assessment by digital photography of whether there is hair regrowth within lesions over time - Mean change in the DLECC scale from Baseline (Day 1) to Week 24 and Week 48 Pharmacodynamics: - Change in the following PD biomarkers from Baseline (Day 1) over time: pDCs (in tissue and blood), IFNa, MxA, and IFN gene signature (in blood) - To explore potential associations of genetic variations, gene expression, and profiles of cells and p | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Czechia, Czech Republic, Denmark, France, Germany, Greece, Israel, Poland, United States
Contacts
Public ContactAdina Kay Knight, MD, Sr. Med. Dir.
Horizon Therapeutics
Outcome results
None listed