The research study is being conducted to learn more about how patients with cutaneous lupus erythematosus (CLE) respond to the use of quinacrine. Quinacrine is a medication that was originally developed and used starting in the 1930's to treat malaria. It has been used for decades to help reduce inflammation in the body. Doctors have observed that quinacrine may also help improve skin symptoms in patients with CLE, a condition in which the immune system mistakenly attacks the skin, causing rashes, sores, and other skin problems. Although some doctors have prescribed quinacrine for CLE based on these observations, it has not yet been formally approved by the U.S. Food and Drug Administration (FDA) for this use. The purpose of this clinical trial is to carefully study how safe and effective quinacrine is for treating CLE, as well as how it works in the body. This can help researchers better understand whether it should become a standard treatment option.

Participation will last for about 28 weeks in total. This study is a randomized, double-blind, placebo-controlled study. "Placebo-controlled" means that participants may receive quinacrine or participants may receive a placebo for the first 12 weeks of the study. A placebo looks like the study drug but contains no active medication. It is used to help find out if the results of the study are due to the study drug or due to something else.

Randomized means participants will be put into the study drug group or the placebo group by chance. Participants have a 1:1 chance of receiving the study drug. This means for every 2 people in the study, 1 will receive the study drug and 1 will receive the placebo. Double-blind means that neither participants nor the study team will know which study group participants have been put in. For the next 12 weeks of the study (Week 12-Week 28), all participants will receive the study drug.

Inclusion Criteria:

1. ≥ 18 years of age at the time of signing the informed consent form.

2. Willing and capable of giving written informed consent, which includes being able to comply with all aspects of the study treatment and assessments schedule, including the ability to receive or self-administer study treatment at home or outside of the study site clinic.

3. Must have diagnosis of SCLE or DLE that has been histologically confirmed (in the past or at Screening), with or without systemic LE manifestations. For participants without historical biopsy data, a skin biopsy must be performed at Screening to confirm CLE diagnosis prior to randomization.

   All participants must also have active skin manifestations that fulfill the following:

4. CLASI-A ≥8 at Screening and randomization

5. Must have active CLE despite an adequate trial of conventional therapies (defined topical corticosteroids and HCQ used for at least 12 weeks prior to Screening) OR previously documented failure to respond to these agents when used for at least 12 weeks OR the requirement to discontinue these agents due to side effects or poor tolerability.

6. If patients are using HCQ during screening, the same dose should be continued until the end of the study.

Exclusion Criteria:

1. Have any medical condition or laboratory abnormality during the Screening Period that, in the opinion of the Investigator, is clinically significant and could interfere with the participant's ability to be included in the study.

2. Have undergone phlebotomy with removal of ≥ 500 mL of blood within 30 days prior to the Screening Visit.

3. Have received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to the Screening Visit.

4. Have participated in any other study involving an investigational product within the last 30 days or 5 half-lives, whichever is greater, prior to the Screening Visit.

5. Subjects receiving treatment with primaquine or any concomitant medication that is a substrate of CYP2D6 at screening or during the study.

6. Subjects receiving concomitant medications that are classified as moderate or strong inhibitors of CYP3A4/5 at screening or during the study.

7. Have any of the following laboratory abnormalities at the Screening Visit (as per the central laboratory)

   1. Aspartate aminotransferase (AST) ≥ 1.5 x~ upper limit of normal (ULN).
   2. Alanine aminotransferase (ALT) ≥ 1.5 x~ ULN.
   3. Total bilirubin ≥ 1.5 ULN. Note: A participant with elevated fasting unconjugated serum bilirubin with documented Gilbert syndrome may be enrolled at the Investigator's discretion.

8. Subjects with eGFR < 45 at the time of screening..

9. Subjects with G6PD deficiency defined as <30% of normal enzyme activity at the time of screening.

10. Have had a cardiovascular event (e.g., acute myocardial infarction, stroke) or revascularization procedure (e.g., percutaneous coronary intervention, coronary artery bypass graft) within 6 months of the Screening Visit.

11. Have evidence of prolonged QT (QTcF > 450 msec for males and > 470 msec for females) on electrocardiogram (ECG) at the Screening Visit.

12. Have a recent serious infection requiring injectable antimicrobial therapy or hospitalization within the 4 weeks prior to Screening Visit or any ongoing febrile illness or infection requiring oral antimicrobial therapy within 1 week of the Screening Visit.

13. Have had any surgical procedure (except for minor procedures) within 4 weeks prior to the Screening Visit.

14. Have known active nephritis or neuropsychiatric SLE.

15. Have current inflammatory skin disease other than SCLE/DLE that, in the opinion of the Investigator, could interfere with the inflammatory skin assessments or confound the disease activity assessments.

16. Use of immunosuppressive or disease-modifying treatments for SLE that were initiated less than 3 months prior to Screening, have not been at a stable dose for at least 1 month prior to Screening.

17. Have received/used any of the following prior medications or undergone any of the following therapeutic procedures:

    1. Use of high-potency topical corticosteroid and/or topical agents (immunosuppressant) for skin lesions within 7 days prior to randomization.
    2. Use of high-potency intralesional corticosteroid within 4 weeks prior to randomization.
    3. JAK or TYK2 inhibitors within 1 month before the visit 1.
    4. IFN1/IFN1R inhibitors within 3 months before the Screening visit.