Ritlecitinib for Vitiligo

(Tranquillo 2 Trial)

Not currently recruiting at 306 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Disqualifiers: Psychiatric conditions, Active infections, Skin diseases, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 28

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medicine called ritlecitinib to determine its safety and effectiveness in treating nonsegmental vitiligo, a condition that causes white patches on the skin. Participants will receive either different doses of ritlecitinib or a placebo (a pill with no active medicine) to compare outcomes. The trial seeks individuals who have had nonsegmental vitiligo for at least 3 months and are willing to stop other vitiligo treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for vitiligo.

Do I have to stop taking my current medications for the trial?

You will need to stop all other treatments for vitiligo, but you can continue taking medications for other conditions as long as your regimen is stable and doesn't change during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ritlecitinib is generally safe based on earlier studies. These studies found that most people with active nonsegmental vitiligo tolerated the medication well over 48 weeks, without serious side effects.

The combined safety data indicate that only a few participants experienced a significant drop in white blood cell count, a rare side effect. Participants aged 65 and older might face a slightly higher risk for this.

Overall, ritlecitinib has been tested in other studies and is considered generally safe, with only a few uncommon side effects reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Ritlecitinib is unique because it targets Janus kinase 3 (JAK3) specifically, offering a novel approach compared to current vitiligo treatments that mainly involve corticosteroids, calcineurin inhibitors, or phototherapy. This targeted action may reduce inflammation and modify immune responses with potentially fewer side effects. Researchers are excited about Ritlecitinib because it represents a potential shift towards more precise and effective treatment for vitiligo, which could improve skin repigmentation outcomes for patients.

What evidence suggests that ritlecitinib might be an effective treatment for vitiligo?

Research has shown that the oral medication ritlecitinib effectively treats nonsegmental vitiligo, a condition causing white patches on the skin. Studies have found that patients experienced a significant return of skin color over 48 weeks. Ritlecitinib targets specific parts of the immune system, potentially preventing the destruction of cells that produce skin color. In this trial, participants will receive different dosages of ritlecitinib or a placebo. When used alone, ritlecitinib produced good results and worked even better when combined with narrow-band UVB light therapy. Overall, ritlecitinib has been well-tolerated and shows promise as a treatment option for vitiligo. ^{1 2 3 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults with nonsegmental vitiligo, which causes white skin patches, can join this trial if they've had the condition for at least 3 months. They must be over 18 and willing to stop other vitiligo treatments. Participants should have a certain amount of body and facial skin affected but not on palms or soles.

Inclusion Criteria

I have been diagnosed with nonsegmental vitiligo for over 3 months.

My skin condition affects 4% to 60% of my body, not including my hands or feet.

I have a skin condition affecting more than half a percent of my face.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Participants receive either 50 mg or 100 mg of ritlecitinib or placebo daily for 52 weeks

52 weeks

At least 17 visits (in-person)

Treatment Part II

Participants receive 100 mg of ritlecitinib daily in a non-randomized open-label extension for 52 weeks

52 weeks

At least 11 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ritlecitinib

Trial Overview

The study tests ritlecitinib's safety and effectiveness against placebo in two parts: Part I compares two doses (50 mg & 100 mg) daily to placebo; non-responders after 52 weeks switch to ritlecitinib. In Part II, all receive only the 100 mg dose. The trial involves regular visits for various tests.

How Is the Trial Designed?

Group I: Arm 4- Ritlecitinib 100mg Experimental Treatment 1 Intervention

Non-randomized open-label Ritlecitinib 100mg QD for 52 weeks.

Group II: Arm 2- Ritlecitinib 50mg Experimental Treatment 1 Intervention

Randomized to Ritlecitinib 50 mg QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status.

Group III: Arm 1- Ritlecitinib 100 milligrams (mg) Experimental Treatment 1 Intervention

Randomized to Ritlecitinib 100 mg QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status.

Group IV: Arm 3- Placebo Placebo Group 1 Intervention

Randomized to Placebo QD for 52 weeks before progressing into the up/down titration extension period, rerandomized according to responder status.

Ritlecitinib is already approved in European Union, United States for the following indications:

Approved in European Union as Litfulo for:

• Severe alopecia areata

Approved in United States as Litfulo for:

• Severe alopecia areata

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Ritlecitinib, an oral Janus kinase inhibitor, is being developed for multiple conditions including alopecia areata and rheumatoid arthritis, with data from 12 clinical trials involving healthy participants and patients collected between 2014 and 2021.

The development of a population pharmacokinetic model for ritlecitinib involved three iterations, leading to a final model that effectively addressed clinical drug development questions and informed the product label, indicating its potential efficacy and safety in various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. Wojciechowski, J., S Purohit, V., Huh, Y., et al.[2023]

Topical ruxolitinib cream has been shown to significantly improve vitiligo symptoms, with 58% of patients achieving a 50% improvement in Vitiligo Area Scoring Index (VASI) after 52 weeks of treatment, making it an effective option for repigmentation.

The treatment has a favorable safety profile, with only mild adverse effects reported, such as erythema and pruritus, and it offers significant clinical improvements compared to traditional therapies, which may have more severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Ruxolitinib for Treatment of Non-Segmental Vitiligo. Hwang, JR., Driscoll, MS.[2023]

Ritlecitinib (LITFULOTM) is an effective treatment for severe alopecia areata, achieving a significant reduction in hair loss as measured by the Severity of Alopecia Tool (SALT) score, with 31% of participants on the 200 mg dose achieving a SALT score of ≤20 after 24 weeks.

The treatment was generally well-tolerated, with mild to moderate side effects such as headache and upper respiratory infections, indicating a favorable safety profile for patients aged 12 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LITFULOTM (Ritlecitinib) Capsules: A Janus Kinase 3 Inhibitor for the Treatment of Severe Alopecia Areata. Gupta, AK., Ravi, SP., Vincent, K., et al.[2023]

In a phase 2 trial involving patients with vitiligo, those using 1.5% ruxolitinib cream showed a significant improvement in facial Vitiligo Area Scoring Index scores, with a mean improvement of 79.9% at week 24 compared to only 1.1% in those who did not respond.

Proteomic analysis revealed distinct inflammatory biomarker profiles between patients who achieved at least a 50% improvement and those who did not, suggesting that these biomarkers could help identify which patients are more likely to benefit from ruxolitinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Levels of Circulating Inflammatory Biomarkers Stratify Patients with Vitiligo Who Significantly Repigment after Treatment with Ruxolitinib Cream. Howell, MD., Kuo, FI., Rumberger, B., et al.[2023]

Topical tofacitinib, a Janus kinase (JAK) inhibitor, was used in combination with phototherapy for 9 months to treat an adolescent patient with long-standing and treatment-resistant vitiligo.

The treatment resulted in near complete repigmentation of the skin, suggesting that JAK inhibitors may be a promising therapy for vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Tofacitinib: A Janus Kinase Inhibitor for the Treatment of Vitiligo in an Adolescent Patient. Berbert Ferreira, S., Berbert Ferreira, R., Neves Neto, AC., et al.[2021]

In a preliminary study involving four patients with progressing vitiligo, treatment with oral baricitinib for 12 weeks resulted in significant re-pigmentation without major side effects, indicating its efficacy and safety.

In laboratory tests, baricitinib enhanced tyrosinase activity and melanin production in damaged melanocytes, suggesting a mechanism of action that could help restore pigmentation in vitiligo patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro. Dong, J., Huang, X., Ma, LP., et al.[2022]

Ritlecitinib, an oral kinase inhibitor developed by Pfizer, was approved in the USA on June 23, 2023, for treating severe alopecia areata in adults and adolescents aged 12 and older.

The drug has also received approval in Japan for intractable cases of alopecia areata and is undergoing regulatory review in the EU, UK, and China, indicating its potential as a significant treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ritlecitinib: First Approval. Blair, HA.[2023]

Combining low-dose tofacitinib with 308-nm excimer laser treatment shows promise as an effective therapy for patients with nonsegmental vitiligo who have not responded to standard treatments.

This combination therapy could offer a new option for patients struggling with vitiligo, potentially improving their skin condition when other therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose tofacitinib with 308-nm excimer therapy successfully induced repigmentation in patients with refractory vitiligo. Fang, WC., Lin, SY., Huang, SM., et al.[2022]

In a phase 2 study involving 157 adults with vitiligo, ruxolitinib cream demonstrated significant efficacy, with 45% of patients using the 1.5% twice daily dose achieving at least a 50% improvement in facial vitiligo area by week 24, compared to only 3% in the control group.

The treatment was well tolerated, with most adverse events being mild to moderate, suggesting that ruxolitinib cream could be a safe and effective option for repigmentation in vitiligo patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Rosmarin, D., Pandya, AG., Lebwohl, M., et al.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36370907/

Efficacy and safety of oral ritlecitinib for the treatment ...

Conclusions: Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo. Keywords: JAK inhibitor; JAK/STAT ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0190962222029899

Efficacy and safety of oral ritlecitinib for the treatment ...

Conclusions. Oral ritlecitinib was effective and well tolerated over 48 weeks in patients with active nonsegmental vitiligo.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06163326

NCT06163326 | A 52-Week Study to Learn About the ...

This study is to evaluate how safe and effective ritlecitinib is in participants with non-segmental vitiligo (NSV).

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39709084/

Response to ritlecitinib with or without narrow-band ...

Ritlecitinib alone and with nbUVB therapy improved facial and total body repigmentation and was well tolerated. Adding nbUVB may improve ritlecitinib efficacy.

5.

dermatologytimes.com

dermatologytimes.com/view/oral-ritlecitinib-plus-nbuv-b-accelerates-repigmentation-in-nonsegmental-vitiligo

Oral Ritlecitinib Plus nbUV-B Accelerates Repigmentation ...

Specifically, combination therapy led to a 69.6% mean improvement in facial repigmentation vs 55.1% with ritlecitinib monotherapy. Moreover, the ...

6.

litfulo.pfizerpro.com

litfulo.pfizerpro.com/safety/pooled-safety-data

Pooled Safety Data

Confirmed ALC <500/mm 3 occurred in 1 (<0.1%) subject treated with LITFULO 50 mg · Age appeared to be a risk factor in patients ≥65 years of age.

7.

pfizerclinicaltrials.com

pfizerclinicaltrials.com/find-a-trial/nct06163326-vitiligo-trial

Clinical Trial for Vitiligo. | Pfizer

This study is to evaluate how safe and effective ritlecitinib is in participants with non-segmental vitiligo (NSV).