A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ALD-102 Solution in Subjects With Alopecia Areata

A Phase 1B/2A, Intraindividual Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ALD-102 Solution for Intradermal Injection in Subjects With Alopecia Areata

The goal of this first-in-human clinical trial is to learn if ALD-102 Solution is safe and well tolerated following injections in the scalp in subjects with alopecia areata. The study will also learn about the effect of ALD-102 on hair regrowth in treatment areas. The researchers will compare the effects of ALD-102 Solution (drug) to placebo (saline solution that contains no drug) or an untreated area. Study participants will have treatment areas selected on the scalp to receive ALD-102 Solution (drug), placebo (saline solution) or to remain untreated. Injections will occur once every 4 weeks for a treatment period of 8 weeks.

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria, either at the screening and Day 1 visits or only at 1 of the specified visits (screening or Day 1) as noted in the criterion:

1. Male or female subject aged 18 to 55 years, inclusive, at the time of informed consent.

2. Subject has a body mass index (BMI) between 18.0-35.0 kg/m2, inclusive, at screening.

3. Subject has a body weight ≥ 50 kg, inclusive, at screening.

4. Subject has a clinically confirmed diagnosis of AA at screening visit, based on investigator's judgement.

5. For the treatment area(s) receiving ALD-102 Solution: subject must have AA lesion(s) that can accommodate the required number of injections per cohort: 20 injections for Cohorts 1#-3# and 40 injections for Cohort 4#.

   • A single scalp lesion of AA should preferably be selected as the treatment area to receive all injections.

     • For Cohorts 1#-3#: a total of 20 injections requires a scalp treatment area of 12 cm2 (1.86 in2).
     • For Cohort 4#: a total of 40 injections requires a scalp treatment area of 28 cm2 (4.34 in2).

   • If a single scalp lesion of AA cannot accommodate the full number of required injections per cohort, multiple scalp treatment areas may be selected:

     - In such cases, each scalp treatment area must be large enough to accommodate at least 6 injections (2 cm2 [0.31 in2]).

   • All selected treatment area(s) must display a near-complete or complete absence of terminal hairs and should be clinically similar, as judged by the investigator.

6. For the control area:

   • Cohorts 1# and 2#: subjects must have a control AA scalp lesion selected measuring approximately 2 cm² (0.31 in2) to receive 6 placebo injections. This area should be located ≥ 6 cm from the designated treatment area(s), exhibit a near-complete or complete absence of terminal hairs, be clinically similar to the selected treatment area(s) as judged by the investigator, and preferably be positioned contralaterally to one of the selected treatment areas.
   • Cohorts 3# and 4#: subjects must have an untreated AA scalp lesion selected measuring at least 2 cm² (0.31 in2). This area should be located ≥ 6 cm from the designated treatment areas, exhibit a near-complete or complete absence of terminal hairs, be clinically similar to the selected treatment area(s) as judged by the investigator, and preferably be positioned contralaterally to one of the selected treatment areas.

7. Duration of current episode of hair loss at the treatment and control areas > 6 months but < 5 years at screening and Day 1, along with investigators' assessment that hair regrowth is possible. Total duration of current episode of hair loss outside of treatment and control areas and total duration since diagnosis of AA could be > 5 years.

8. No evidence of active regrowth or hair loss present at baseline and no known history of significant regrowth or hair loss, as per investigator's judgement, over the last 6 months.

9. Subject is willing to keep the same hairstyle and color (eg, hair products, process, and timing for hair appointments) for the duration of the trial.

   Note: Hair dying and shaving of scalp is allowed during the trial but not within 2 weeks prior to a study visit.

10. For female subject of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective contraceptive method in addition to use of condom for their non-vasectomized male partner(s) from ≥ 4 weeks prior to Day 1 until ≥ 16 weeks after the last injection, and refrain from egg retrieval/egg donation during this period. Highly effective contraceptive methods include hormonal contraceptives (eg, combined oral contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine systems, 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 with diaphragm, and male condom with contraceptive sponge) in conjunction with spermicide.

    Note: Subjects must have been on a stable dose of hormonal contraceptives for ≥ 4 weeks before Day 1.

    Note: The above list of contraceptive methods does not apply to subjects who are abstinent for ≥ 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal intercourse throughout the trial or for ≥ 16 weeks after the last injection. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable.

    Note: A female subject of nonchildbearing potential is defined as follows:

    • Female subject who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
    • Female subject who has had a cessation of menses for ≥ 12 months prior to the screening visit without an alternative medical cause, and a follicle-stimulating hormone (FSH) test confirming nonchildbearing potential (refer to laboratory reference ranges for confirmatory levels).

11. For male subject involved in any sexual intercourse that could lead to pregnancy, subject must agree to use a condom and their female partner must use one of the highly effective contraceptive methods listed in Inclusion Criterion #10, from Day 1 until ≥ 16 weeks after the last injection and refrain from donating sperm during this period. If the female partner of a male subject uses any of the hormonal contraceptive methods listed above, this contraceptive method should be used by the female partner from ≥ 4 weeks before Day 1 until ≥ 16 weeks after the last injection.

12. Female subject of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at Day 1.

13. Subject is willing to participate and is capable of giving a signed and dated informed consent.

    Note: Consent must be obtained prior to any study-related procedures.

14. Subjects must be willing to comply with all study procedures and must be available for the duration of the study.

15. Subjects must be willing to receive approximately 20 to 40 intradermal injections every 4 weeks (number of injections will vary for each cohort).

Exclusion Criteria:

A subject who meets any of the following criteria at the screening and/or Day 1 visits, as applicable, will be excluded from participation in this study:

1. Very severe AA, defined by SALT score ≥ 95 at screening and/or Day 1, including alopecia universalis and alopecia totalis.

2. Presence of another form of alopecia (eg, androgenetic alopecia [AGA], traction and scarring alopecia, telogen effluvium).

   Note: Subjects with AGA are permitted only if the disorder is clinically distinct, physically separate, and does not affect or interfere with treatment or assessment of the selected treatment and control area(s) of AA. The diagnosis of AA should be clear and unambiguous, and the pattern and location of AGA should not overlap with or compromise the evaluation of the selected treatment and control areas of AA.

3. Presence of diffuse type of AA. Note: Subjects with presence of ophiasis or siapho patterns of AA are allowed.

4. History or presence of hair transplants.

5. History or presence of micropigmentation of the scalp. Note: microblading of the eyebrows is permitted.

6. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.

7. Subject is known to have immune deficiency or is immunocompromised.

8. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.

9. Subject had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.

10. Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with the interpretation of trial results.

11. Subject has a positive result for hepatitis B virus (HBV; positive for hepatitis B surface antigens [HBsAg] or positive for hepatitis B antibodies to core antigens [anti-HBc]; subjects having a negative HBsAg and a positive anti-HBc may enroll if they have a positive hepatitis B surface antibody [anti-HBs] demonstrating natural immunity), hepatitis C virus (HCV; positive for HCV antibodies; however, a subject with documented proof of cure from HCV may be enrolled), or human immunodeficiency virus (HIV).

12. Subject has a current or recent clinically serious viral, bacterial, fungal, or parasitic infection, including but not limited to the following:

    1. History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1;
    2. Have active chronic or acute skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections within 1 week prior to Day 1;
    3. History (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster;
    4. Known active tuberculosis (TB) or a positive TB infection test at screening. Subject will be evaluated for latent TB infection with a purified protein derivative (PPD) test or a QuantiFERONTB Gold test. Subjects who demonstrate evidence of latent TB infection (either PPD ≥ 5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of Bacillus Calmette-Guérin vaccination status) will only be allowed to participate in the study if there is documented evidence of a completed adequate treatment course for latent TB (with negative chest x-ray findings for active TB).

    Note: A recent viral upper respiratory tract infection or uncomplicated urinary tract infection should not be considered clinically serious.

13. At screening, any of the following (tests may be repeated once within the same screening period to confirm results prior to Day 1):

    1. Absolute neutrophil count < 1.5 x 109/L;
    2. Absolute lymphocyte count < 0.5 x 109/L;
    3. Hemoglobin < 11.0 g/dL or hematocrit < 30%;
    4. Platelet count < 100 x 109/L;
    5. Clinically significant abnormal estimated creatinine clearance as per investigator judgement (eg, < 90 mL/min based on the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) or serum creatinine value > 1.5 times the upper limit of normal (ULN);
    6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x the ULN;
    7. Total bilirubin ≥ 1.5 x ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN.

14. Subject has a history of clinically significant heart disease in the opinion of the investigator (eg, cardiomyopathy, major congenital heart disease, Wolff-Parkinson-White syndrome, heart attack, stroke, or blood clots).

15. Subject is currently receiving anti-coagulants or medications known to cause thrombocytopenia (unless considered safe by the investigator to stop and washout for the duration of the study).

16. Active forms of other inflammatory skin disease(s) or evidence of other skin conditions on the scalp (eg, psoriasis, seborrheic dermatitis, lupus) at screening and/or Day 1, that in the opinion of the investigator might interfere with evaluation of hair regrowth.

17. Subject has presence of any tattoos, scratches, open sores, or skin damages in the target treatment or control areas that, in the opinion of the investigator, may interfere with study evaluations.

18. Subject is currently treated or was treated within 4 weeks prior to Day 1 with any systemic treatment or oral medication for inflammatory condition that in the opinion of the investigator might interfere with the safety or efficacy assessments; short half-life medications like ibuprofen, paracetamol, and antihistamines are acceptable.

19. Subject is currently receiving a nonbiological investigational product or device or has received one within 4 weeks prior to Day 1.

20. Subject has received a live or live-attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live or live-attenuated vaccine during the study and up to 4 weeks or 5 half-lives (of the study product), whichever is longer, after the last study product administration.

21. Use of systemic and/or intralesional steroids within 8 weeks of Day 1 visit. Note: Intranasal and inhaled corticosteroids are allowed. Eye and ear drops containing corticosteroids are also allowed.

22. Use of systemic treatments including, but not limited to, anthralin, squaric acid, diphenylcycloprophenone (DPCP), dinitrochlorobenzene (DCNB), tacrolimus, minoxidil, or any other medication which in the opinion of the investigator may affect hair regrowth within 4 weeks of Day 1 visit.

23. Subject has received any ultraviolet (UV)-B phototherapy (including tanning beds), has had psoralen-UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Day 1.

24. Topical medicated treatment on the scalp that could affect AA including, but not limited to, topical corticosteroids, calcineurin inhibitors, minoxidil, JAK inhibitors, medical devices within 2 weeks prior to Day 1 visit.

    Note: Topical medicated treatments are permitted outside of the scalp.

25. Subject has previously used a systemic JAK inhibitor for their AA (eg. baricitinib, ritlecitinib, deuruxolitinib) and discontinued for lack of efficacy (information obtained from medical chart or subject's physician, or directly from the subject).

    Note: Subjects that used a systemic JAK inhibitor for AA and discontinued for another reason than lack of efficacy, or used a systemic JAK inhibitor for another reason than AA, are allowed but must have discontinued the systemic JAK inhibitor at least 6 months prior to Day 1.

26. Use of platelet-rich plasma injections in the last 12 weeks prior to Day 1.

27. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half-lives (whichever is longer) prior to Day 1.

28. Subject who has had previous treatment with any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, or ofatumumab) or other B-cell targeting therapy (eg, belimumab) within 12 months before Day 1.

29. Subject who has received previous treatment with pDC inhibiting therapies (eg, anti immunoglobulin-like transcript [ILT]7, anti-blood dendritic cell antigen 2 [BDCA2]).

30. Subject has received any prescription products containing exogenous androgens, including but not limited to testosterone, or anabolic-androgenic steroids, within the past 6 months before Day 1.

    Note: There is no washout period for over-the-counter (OTC), supplements, and/or herbal product that can contain exogenous androgens or can affect hair regrowth. However, if the subject is using any of these products for the purpose of AA, they must stop using the products at the time of informed consent and for the duration of the trial.

31. Subject has a known or suspected allergy to ALD-102 or any component of the investigational product.

32. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to Day 1.

33. Subject has a history of an allergic reaction or significant sensitivity to lidocaine or other local anesthetics.

34. Subject has a history of hypertrophic scarring or keloid formation in scars or suture sites.

35. Subject has taken anticoagulant medication, such as heparin, low molecular weight (LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin ≤ 81 mg which will be allowed), within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. Short half-life nonsteroidal anti-inflammatory drugs (NSAIDs) will not be considered antiplatelets and will be allowed.

36. Subject is not able to tolerate intradermal injection or has a known sensitivity to needle injection.

37. Subject is institutionalized because of legal or regulatory order.