Ritlecitinib for Vitiligo

(Tranquillo 2 Trial)

Recruiting at 236 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

1450 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing ritlecitinib, a medicine for treating vitiligo, in adults with nonsegmental vitiligo. The medicine works by protecting skin color cells from being destroyed by the immune system. The study will compare ritlecitinib to see if it is safe and effective. Ritlecitinib is being tested for its efficacy in treating alopecia areata and 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.

What data supports the effectiveness of the drug Ritlecitinib for treating vitiligo?

Research on similar drugs, like ruxolitinib and tofacitinib, which are also Janus kinase (JAK) inhibitors, shows they can help repigment skin in people with vitiligo. This suggests that Ritlecitinib, which works in a similar way, might also be effective. ^{1 2 3 4 5}

Is Ritlecitinib safe for humans?

Ritlecitinib has been tested in humans for conditions like alopecia areata, and common mild to moderate side effects include headache, nasopharyngitis (common cold), and upper respiratory tract infection. ^{4 6 7 8 9}

How is the drug Ritlecitinib unique for treating vitiligo?

Ritlecitinib is unique because it is an oral medication that works by inhibiting specific enzymes (Janus kinase 3 and tyrosine kinase) involved in the immune response, which may help prevent the immune system from attacking skin cells, potentially aiding in repigmentation for vitiligo patients. ^{2 4 6 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Low-dose tofacitinib with 308-nm excimer therapy successfully induced repigmentation in patients with refractory vitiligo. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Topical Tofacitinib: A Janus Kinase Inhibitor for the Treatment of Vitiligo in an Adolescent Patient. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Review of Ruxolitinib for Treatment of Non-Segmental Vitiligo. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Baseline Levels of Circulating Inflammatory Biomarkers Stratify Patients with Vitiligo Who Significantly Repigment after Treatment with Ruxolitinib Cream. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Ritlecitinib: First Approval. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evolution of Ritlecitinib Population Pharmacokinetic Models During Clinical Drug Development. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

LITFULOTM (Ritlecitinib) Capsules: A Janus Kinase 3 Inhibitor for the Treatment of Severe Alopecia Areata. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. [2021]