A Phase 2 trial to evaluate the efficacy and safety of daxdilimab in participants with primary discoid lupus erythematosus.
- Conditions
- Primary Discoid Lupus ErythematosusMedDRA version: 25.0Level: LLTClassification code: 10013072Term: Discoid lupus erythematosus Class: 10040785Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 92
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., 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., 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
Individuals involved in the conduct of the trial, their employees, or immediate family members of such individuals., 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: -In situ carcinoma of the cervix treated with apparent success with curative therapy > 12 months prior to Screening, or -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 ., Participation in another clinical trial with an investigational drug within 4 weeks prior to Randomization or within 5 published half-lives, whichever is longer., Active tuberculosis (TB), or a positive IFN? 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.,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of daxdilimab compared with placebo in reducing active disease activity at Week 24 in participants with primary DLE.;Secondary Objective: 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.;Primary end point(s): Primary Efficacy: Mean change in CLASI-A score from Baseline (Day 1) to Week 24
- Secondary Outcome Measures
Name Time Method 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]).;Secondary end point(s):Secondary Efficacy: Proportion of participants who achieve a = 50% reduction in CLASI-A score from Baseline (Day 1) at Week 24.;Secondary end point(s):Secondary Efficacy: Mean change in the SADDLE from Baseline (Day 1) to Week 24.;Secondary end point(s):Pharmacokinetics and Immunogenicity: Serum concentration of daxdilimab over time.;Secondary end point(s):Pharmacokinetics and Immunogenicity: Incidence of ADA directed against daxdilimab over time.;Secondary end point(s):Safety: Incidence of TEAEs.;Secondary end point(s):Safety: Incidence of TESAEs;Secondary end point(s):Safety: 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).