Combination Approach With Ritlecitinib and nbUVB Compared to Ritlecitinib Alone for Treating Vitiligo Prospective Multicentric Evaluator Blinded Interventional Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 5
- 主要终点
- The Facial Vitiligo Area Scoring Index (F-VASI)
研究概览
简要总结
Vitiligo affects approximately 1 to 2% of the global population and significantly impacts people's quality of life. areas of high stress. Ritlecitinib, an orally administered inhibitor of JAK3 (Janus kinase)/ TEC (tyrosine kinase expressed in hepatocellular carcinoma) has shown effectiveness and safety for the treatment of vitiligo. In a phase 2b trial, three doses of ritlecitinib, 200/50 mg, 100/50 mg, and 50 mg, were all statistically significant versus placebo on the Facial Vitiligo Area Scoring Index (F-VASI) at week 24 in patients with active NSV. Considering that the immune process primarily contributes to depigmentation while ultraviolet (UV) radiation stimulates the differentiation and proliferation of melanocyte stem cells for re-pigmentation, the investigators propose that a combination therapy using ritlecitinib and narrowband UVB (nbUVB) could offer an optimal approach for treating vitiligo patients.
The primary objective is thTo compare between the groups, the mean percentage change from baseline in F-VASI and T-VASI at week 52.
Following central randomization, patients will be assigned to receive either ritlecitinib 100mg daily (QD) or a combined therapy using ritlecitinib 100mg QD + twice weekly narrowband UVB treatment for a duration of 52 weeks. At the end of this period, all participants will continue for the open-label phase, receiving ritlecitinib 100mg QD. Eligible participants will be stratified by Fitzpatrick Skin Type (FST, also known as phototype). More specifically, there will be 2 strata based on FST targets: (1) FST I to III (2) FST I IV, to VI. Each FST stratum will target to enroll at least 50% participants into the study population. Stratified randomization across FST sub-groups will support the evaluation of a consistent benefit-risk profile across all FST strata. Enrollment of participants with active or stable nonsegmental vitiligo will be proactively managed without formally capping or stratifying.
Throughout the study, there will be a total of 8 visits conducted: selection, inclusion, week 4, week 12, week 24, week 36, week 52 and week 72. In patients who volunteer, a skin biopsy will be performed on both the lesional and perilesional areas at baseline, week 4 and week 52. We aim to include between 12 and 20 volunteer patients. Serum and plasma samples will be collected at the screening visit, week 4, week 12, week 24, week 36, week 52 and week 72.
A pregnancy test will be performed every 4 weeks i.e. at weeks 8, 16, 20, 28, 32, 40, 44, 48, 56, 60, 64 and 68;
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Men and women with non-segmental vitiligo.
- •Age ≥ 18 age old
- •BSA involvement between 4% and 60% inclusive, excluding involvements at palms of the hands, soles of the feet, or dorsal aspect of the feet
- •BSA ≥0.5% involvement on the face (face is defined as including the area on the forehead to the original hairline, on the cheek vertically to the jawline, and laterally from the corner of the mouth to the tragus. The face will not include scalp, ears, neck, or surface area of the lips, but will include the nose and the eyelids)
- •F-VASI ≥0.5 and T-VASI ≥3
- •Active and stable vitiligo
- •For Women of childbearing potential (WOCBP), an effective contraception (estroprogestative pill, contraceptive implant, IUD, condoms or tubal ligation) should be used for more than one month before the inclusion in the study; Women of childbearing potential (WOCBP) must have a negative urine pregnancy test result at baseline; WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives;
- •Women of non-childbearing potential (WONCBP) do not require a urine pregnancy test and must meet at least one of the following criteria:
- •o Have undergone hysterectomy or bilateral oophorectomy;
- •Have medically confirmed ovarian failure; or
- •Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause);
- •Affiliation to a social security system;
- •Signed informed consent.
排除标准
- •1. Pregnant or breast-feeding women. Or women with potential childbearing and not taking contraceptives or who plan to get pregnant during the study duration, and
- •Segmental or mixed vitiligo, and
- •Contraindication to nbUVB phototherapy, and
- •Concomitant use of topical or systemic immunosuppressive medication or steroids, and
- •Patients treated before with oral JAK inhibitor, topical treatments (including JAK inhibitors) that could affect vitiligo (eg, corticosteroids, vitamin D3 and calcineurin inhibitor) within 2 Weeks of Day 1 (Baseline) and during the study
- •At any time prior to or during the study:
- •Use of permanent depigmentation treatment for vitiligo and/or other types of pigmentation disorder (eg, monobenzone or phenol).
- •Previous use of any systemic JAK inhibitor for any disease indication
- •Any non-B cell selective lymphocyte depleting agent (eg, alefacept, alemtuzumab) and alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc.
- •History of MKTP or other surgical treatment for vitiligo.
- •Within 6 months of the first dose of study drug or 5 half-lives (if known), or until lymphocyte count returns to normal, whichever is longer and during the study:
- •- Any B-cell-depleting agents including but not limited to rituximab or previously receiving leukocyte apheresis, including selective lymphocyte, monocyte, or granulocyte apheresis, or plasma exchange.
- •Within 12 weeks of first dose of study drug or 5 half-lives (if known), whichever is longer and during the study:
- •Other immunomodulatory biologic agents or other marketed immunosuppressants.
- •IL12/23 inhibitor (eg, ustekinumab)
- •Integrin inhibitors (eg, vedolizumab)
- •Within 8 weeks of Day 1 and during the study:
- •- Narrow-band UVB phototherapy, Psoralen Ultra-Violet A therapy, or other phototherapy.
- •TNF inhibitors (or biosimilars thereof) as described below:
- •Infliximab;
- •Adalimumab;
- •Golimumab
- •Interferon therapy
- •Within 8 Weeks of Day 1 [Baseline] (or within 5 half-lives, whichever is longer) and during the study:
- •Systemic treatments that could affect vitiligo.
- •Use of oral or intravenous immune suppressants (eg, cyclosporine A, tacrolimus, azathioprine, MTX, systemic corticosteroids, mycophenolate-mofetil, mercaptopurine (6MP), or thioguanine).
- •Use of sulfasalazine.
- •Intralesional, oral or injectable steroids.
- •Within 6 Weeks of Day 1 (Baseline), during the study, and within 6 weeks of last dose:
- •- Vaccination with live attenuated, replication-competent vaccine; Current routine household contact with individuals who have been vaccinated with a live attenuated, replication-competent vaccine.
- •Within 4 weeks (28 Days) of first dose of study intervention or 5 half-lives (if known), whichever is longer and during the study:
- •Prohibited CYP3A inducers (see Table 8).
- •Herbals that are known to have an effect on drug metabolism.
- •Previous administration of investigational drug(s) or vaccines that do not affect vitiligo.
- •Note: Any investigational or experimental therapy taken, or procedure performed for vitiligo and other autoimmune or immunologic diseases including but not limited to rheumatoid arthritis, psoriasis alopecia areata, thyroid disease, allergic rhinitis, or atopic dermatitis within the previous 1 year should be carefully evaluated. Participants cannot participate in studies of other investigational or experimental therapies or procedures at any time during their participation in this study.
- •Within 1 Week of Day 1 [Baseline] (or within 5 half-lives, whichever is longer) and during the study:
- •- Herbal medications with unknown properties or known beneficial effects for vitiligo.
- •Prohibited CYP3A substrates as described in Table
- •Investigators should consult the SRSD for ritlecitinib for information regarding medication that is prohibited for concomitant use.
- •Investigators should consult the product label for any other medication used during the study for information regarding medication that is prohibited for concomitant use.
- •Patients suffering from photodermatosis or taking photosensitive drugs, and
- •Patients with more than 33% of leucotrichia on the lesions (Leukotrichia in more than 33% of the face surface area affected with vitiligo lesions OR leukotrichia in more than 33% of the total body surface area affected with vitiligo lesions), and
- •Personal history of skin cancer, and
- •Personal history of any malignancies or a history of malignancies with the exception of adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ will be excluded from the study, and
- •Patients with active infection or other systemic/ inflammatory disease, and
- •Tuberculosis or latent tuberculosis, and
- •Vulnerable people: pregnant or breast-feeding women, minors, adult under guardianship, deprived of freedom or with psychiatric condition, and
- •Participants in other clinical therapeutic studies involving a drug that could interfere with the present evaluation.
- •14. Participants are excluded from the study if any of the following criteria apply: i. Medical Conditions:
- •Any psychiatric condition including recent or active suicidal ideation or behavior that meets any of the following criteria:
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研究组 & 干预措施
Drug and UVB
patients will be assigned to receive a combined therapy using ritlecitinib 100mg QD + twice weekly narrowband UVB treatment for a duration of 52 weeks.
干预措施: LITFULO and UVB (Procedure)
Drug alone
Patients will be assigned to receive either ritlecitinib 100mg daily (QD)
干预措施: LITFULO (Drug)
结局指标
主要结局
The Facial Vitiligo Area Scoring Index (F-VASI)
时间窗: at week 52
To compare the proportion of patients treated with combined ritlecitinib + nbUVB versus ritlecitinib monotherapy achieving The Facial Vitiligo Area Scoring Index (F-VASI) -75 at week.
Total Body Vitiligo Scoring Index (T-VASI) 50
时间窗: at week 52
To compare the proportion of patients treated with combined ritlecitinib + nbUVB versus ritlecitinib monotherapy achieving T-VASI50 at week 52
次要结局
- The quality of life(during 52 weeks)
- Safety treatment(during 52 weeks)