A Phase III Clinical Study to Evaluate the Efficacy and Safety of MH004 Ointment in Non-segmental Vitiligo

A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of MH004 Ointment in Adolescent and Adult Subjects With Non-segmental Vitiligo

This is a randomized, double-blind, multicenter, placebo-controlled clinical study intended to evaluate the efficacy, safety and population pharmacokinetic profiles of MH004 ointment in eligible participants with NSV.

The study consists of a screening period, a treatment period and a follow-up period, with the treatment period divided into two phases. In Double-blind Treatment Phase (24 weeks, D1 to W24), participants will be randomized at a 2:1 ratio to receive either MH004 ointment or placebo. And in Extended Treatment Phase (28 weeks, W25 to W52), after all participants complete all assessments prior to dosing at W24, they will enter the extended treatment phase and receive 1.0% MH004 ointment with the same dosing regimen as that in the double-blind treatment phase, administered twice daily (BID) until W52. Upon completion of study treatment, all participants will enter a 4-week safety follow-up period. The primary objective of this trial is the proportion of participants achieving at least a 75% improvement from baseline in the Facial Vitiligo Area Scoring Index at Week 24 (F-VASI75).

Inclusion Criteria:

1. Subjects aged 12 to 75 years inclusive at the time of signing the Informed Consent Form (ICF), with no restriction on gender.
2. Clinically diagnosed with non-segmental vitiligo.
3. Prior to study drug administration, participants with vitiligo shall meet the following criteria regarding vitiligo lesion area: Facial lesion area ≥ 0.3% body surface area (BSA), and Facial Vitiligo Area Scoring Index (F-VASI) score ≥ 0.3.
4. Agree to discontinue all vitiligo therapeutic medications and interventions from the time of ICF signature until the end of the last study visit. Over-the-counter (OTC) drugs shall not exert therapeutic effects on vitiligo or interfere with skin pigmentation, including corticosteroids and other immunomodulators. Final eligibility of such OTC drugs shall be determined by the Investigator. Camouflaging makeup is permitted.
5. Women of Childbearing Potential (WOCBP) and male participants whose partners are WOCBP must agree to use reliable contraceptive methods throughout the trial period and for 28 days after the last study drug administration (abstinence, prior sterilization, oral contraceptives, and/or barrier methods [condoms, diaphragms, cervical caps, etc.]). For WOCBP, the human chorionic gonadotropin (hCG) pregnancy test result at the screening visit and prior to the first drug administration at the baseline visit must be negative. Male participants shall not donate sperm during the trial and for 3 months after study completion or drug discontinuation.
6. The participant and/or their legal guardian shall fully understand the trial content, requirements and procedures, voluntarily participate in this clinical trial and sign the ICF, and be willing and able to comply with scheduled visits, treatment regimens, laboratory tests and other study procedures throughout the trial.

Exclusion Criteria:

1. All terminal hairs (i.e., beard, eyebrows, eyelashes) within facial vitiligo areas are depigmented white.

2. Other subtypes of vitiligo or hypopigmentary disorders

   1. Segmental vitiligo, unclassified vitiligo, or mixed vitiligo;
   2. Other differential diagnoses of vitiligo or other cutaneous hypopigmentary diseases (e.g., piebaldism, pityriasis alba, nevus anemicus, post-inflammatory hypopigmentation, chemical leukoderma, tinea versicolor, etc.).

3. Specific prior treatment history:

   1. Prior use of any JAK inhibitor (systemic or topical) for vitiligo treatment at any time;
   2. Prior depigmentation therapy for vitiligo (e.g., monobenzone), excluding hydroquinone;
   3. Prior melanocyte-keratinocyte transplantation or other surgical procedures for vitiligo on the face.

4. Treatments administered within the required washout period

   1. Use of biologic agents within 12 weeks or 5 half-lives (whichever is longer) prior to the first study drug administration;

   2. Receipt of laser therapy or any form of phototherapy (including tanning beds) within 8 weeks prior to the first study drug administration;

   3. Within 4 weeks prior to the first study drug administration:

      Systemic immunomodulators (e.g., corticosteroids, methotrexate, cyclosporine, etc.); Systemic medications that may affect vitiligo (e.g., melanocyte-stimulating agents, tetracyclines, methoxsalen, etc.); Administration of live or live-attenuated vaccines;

   4. Oral traditional Chinese medicines for vitiligo within 2 weeks prior to the first study drug administration;

   5. Topical agents applied to vitiligo lesions within 1 week prior to the first study drug administration (e.g., corticosteroids, calcineurin inhibitors, PDE4 inhibitors, retinoids, vitamin D3 analogues, or topical Chinese herbal preparations);

5. Temporary tattoos within vitiligo lesions within 30 days before the first dose (excluding vinyl adhesive tattoos), or any permanent tattoos previously placed within vitiligo lesions.

6. Concomitant diseases or medical history that may interfere with the study

7. Specific risks of cardiovascular and thromboembolic events

8. Active or latent infections

9. Positive virology screening results at screening

10. History of malignancy

11. Clinically significant abnormal laboratory values

12. Subjects planning major invasive procedures during the study, or with prior or planned organ transplantation requiring long-term immunosuppressants (e.g., kidney or liver transplantation).

13. Planned administration of live or live-attenuated vaccines during the study period.

14. Female subjects who are pregnant or breastfeeding.

15. Participation in another interventional drug clinical trial within 3 months or at least 5 half-lives (whichever is longer) prior to randomization; or participation in a medical device clinical trial within 3 months prior to randomization.

16. Hypersensitivity and intolerance Known hypersensitivity to the investigational product or any excipient components.

17. Other exclusion factors

    1. History of alcohol abuse or substance misuse;
    2. Subjects shall avoid intentional excessive sun exposure during the study (e.g., prolonged sunbathing, sun exposure for tanning purposes);
    3. Body mass index (BMI) < 16 kg/m² or > 40 kg/m², where BMI = weight (kg) / height² (m²);
    4. Any other conditions deemed inappropriate for study participation by the Investigator.