Study of Daxdilimab (HZN-7734) in Participants With Moderate-to-Severe Primary Discoid Lupus Erythematosus

Key Inclusion Criteria:

• Willing and able to understand and provide written informed consent.

• Willing and able to comply with the prescribed treatment protocol and evaluationsfor the duration of the trial.

• A diagnosis of DLE for ≥ 6 months prior to screening supported by a history of:

1. A biopsy or

2. a clinical feature score of ≥ 7 on the DLE Classification Criteria (DLECC)scale.

• Currently active discoid lupus with all the following:

1. Digital photography adjudicated with central reading to confirm a currentlyactive discoid disease lesion.

2. CLASI-A score ≥ 8 related to discoid lesions at Baseline.

• Treatment refractory DLE defined as active disease despite current or historicaltreatment with a systemic treatment.

• Females are eligible to participate if they are not pregnant or breastfeeding, andmeet the contraceptive/barrier requirement(s).

• Males are eligible to participate if they agree to the contraceptive/barrierrequirement(s).

• Vaccination status should be up to date per local standards.

Key Exclusion Criteria:

• Participation in another clinical study with an investigational drug within 4 weeksprior to Randomization or within 5 published half-lives, whichever is longer.

• Any condition that, in the opinion of the Investigator, would interfere withevaluation of the investigational product (IP) or interpretation of participantsafety or trial results.

• Weight > 160 kg (352 pounds) at Screening.

• History of allergy, hypersensitivity reaction, or anaphylaxis to any component ofthe IP or to a previous monoclonal antibody (mAb) or human immunoglobin (Ig)therapy.

• Breastfeeding or pregnant women or women who intend to become pregnant anytime fromsigning the informed consent form (ICF) through 6 months after receiving the lastdose of IP.

• Splenectomy.

• Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks priorto screening through randomization.

• History of clinically significant cardiac disease including unstable angina,myocardial infarction, congestive heart failure within 6 months prior toRandomization; arrhythmia requiring active therapy, except for clinicallyinsignificant extra systoles, or minor conduction abnormalities.

• 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 significantlypredisposes the participant to infection.

• Known history of a primary immunodeficiency or an underlying condition, such asknown human immunodeficiency virus (HIV) infection, or a positive result for HIVinfection per central laboratory.

• Participants with positive hepatitis B serologic test results.

• All participants will undergo testing for hepatitis C antibody (HCVAb) duringScreening.

• 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 interferon-gamma release assay (IGRA) testat screening, unless documented history of appropriate treatment for active orlatent 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 notlimited 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 completelyresolved 12 weeks prior to Randomization.

• Opportunistic infection requiring hospitalization or parenteral antimicrobialtreatment 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 ofthe Investigator, may be at a high risk of COVID-19 or its complications should notbe randomized.

• Systemic lupus erythematosus defined by fulfilling 2020 American College ofRheumatology/European Alliance of Associations for Rheumatology criteria for

• Males are eligible to participate if they agree to the contraceptive/barrier
requirement(s).
 

• Vaccination status should be up to date per local standards.
 
 Key Exclusion Criteria:
 

• Participation in another clinical study 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 investigational product (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 monoclonal antibody (mAb) or human immunoglobin (Ig)
therapy.
 

• Breastfeeding or pregnant women or women who intend to become pregnant anytime from
signing the informed consent form (ICF) through 6 months after receiving the last
dose of IP.
 

• 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.
 

• 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.
 

• 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.
 

• Participants with positive hepatitis B serologic test results.
 

• 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 interferon-gamma 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.
 

• 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.
 

• Systemic lupus erythematosus defined by fulfilling 2020 American College of
Rheumatology/European Alliance of Associations for Rheumatology criteria for
systemic lupus erythematosus (SLE).

• Current diagnosis of a systemic connective tissue disease.

• Current inflammatory skin disease other than DLE, that, in the opinion of theInvestigator, could interfere with the inflammatory skin assessments and confoundthe disease activity assessments.

• Exposure to an experimental drug either 30 days, 5 half-lives of the agent, or twicethe duration of the biological effect of the agent, whichever is longer, prior toRandomization and through the final trial visit.

• Receipt of a live-attenuated vaccine within 4 weeks prior to Randomization.