Ruxolitinib for Alopecia Areata

Overseen By Michail S Lionakis, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Valacyclovir

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: HIV, Hepatitis B/C, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 6

Duration: 32 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if ruxolitinib, a pill that calms the immune system, can help people with APECED and severe hair loss. The medication works by blocking overactive immune signals, which may reduce body attacks and promote hair regrowth. Ruxolitinib has shown promise in treating severe alopecia areata by inducing hair regrowth in patients.

Will I have to stop taking my current medications?

The trial requires that you have not used certain treatments for alopecia in the past 2 months and that you do not use systemic immunosuppressive or immune-modulating agents within 3 months prior to screening. If you are currently on these medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Ruxolitinib for treating alopecia areata?

Research shows that 75% of patients with moderate-to-severe alopecia areata experienced significant hair regrowth after using Ruxolitinib, with an average of 92% hair regrowth. This suggests that Ruxolitinib can be effective in treating this condition. ^{1 2 3 4 5}

Is Ruxolitinib safe for treating alopecia areata?

Ruxolitinib, used for alopecia areata, has been generally well-tolerated in studies, with most side effects being mild. Some common side effects include changes in cholesterol and liver enzymes, and occasional infections, but no serious or fatal outcomes were reported. ^{1 6 7 8 9}

How does the drug ruxolitinib differ from other treatments for alopecia areata?

Ruxolitinib is unique because it targets the JAK-STAT pathway, which is involved in the immune response that causes hair loss in alopecia areata. Unlike other treatments, it has shown significant hair regrowth in patients by reducing inflammation and promoting hair growth signals. ^{1 2 4 7 10}

Research Team

Michail S Lionakis, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

This trial is for people aged 12-65 with APECED and severe alopecia areata, meaning they've lost at least half their scalp hair. They haven't seen any hair regrowth recently, haven't treated their alopecia in the last two months, and have had hair loss for over six months. Participants must be up-to-date on vaccinations, willing to use herpes prevention medication and contraception if necessary, and able to give informed consent.

Inclusion Criteria

I am willing to take medication to prevent herpes reactivation.

Participants who can get pregnant or impregnate their partner must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at screening until 12 weeks after the last dose

I have APECED and severe alopecia with over 50% scalp hair loss.

Exclusion Criteria

Current or recent use of any investigational drug

My hair loss diagnosis is uncertain or hard to measure.

You have had a bad reaction to ruxolitinib or similar medications in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Observation

Participants undergo an 8-week observation period to assess baseline disease state

8 weeks

Treatment

Participants receive oral ruxolitinib twice daily for 8 months with dose adjustments at weeks 8 and 16

32 weeks

5 visits (in-person), 6 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ruxolitinib

Trial Overview The study tests Ruxolitinib's effectiveness in promoting hair regrowth in patients with autoimmune-related severe alopecia areata. Over a period of up to 10 months, participants will take Ruxolitinib orally twice daily for eight months while undergoing various assessments including physical exams, blood tests, tissue samples from the scalp and other areas, as well as telehealth check-ins.

Participant Groups

Group I: Ruxolitinib/APECED-AA Patients Experimental Treatment 1 Intervention

All participants receiving IP through this protocol (APECED-AA patients)will receive ruxolitinib.

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

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

In a pilot study involving 12 patients with moderate-to-severe alopecia areata, 75% experienced significant hair regrowth (average of 92%) after treatment with the oral JAK1/2 inhibitor ruxolitinib for 3-6 months.

The treatment was well-tolerated with no serious adverse effects reported, and gene expression analysis indicated a reduction in inflammatory markers associated with the disease, suggesting a mechanism of action that targets the autoimmune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. Mackay-Wiggan, J., Jabbari, A., Nguyen, N., et al.[2023]

Ruxolitinib, a JAK1/2 inhibitor, effectively modulated inflammatory changes in human dermal papilla cells (hDPCs) associated with alopecia areata by blocking the JAK-STAT pathway, which may help in restoring hair growth.

The treatment also stimulated key growth factors and activated the Wnt/β-catenin signaling pathway, promoting signals necessary for hair follicle re-entry into the growth phase, while preserving immune privilege in hair follicles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells. Kim, JE., Lee, YJ., Park, HR., et al.[2021]

In two phase III trials involving 855 adults with severe alopecia areata, baricitinib treatment over 52 weeks led to significant hair regrowth, with 40.9% of patients achieving a SALT score ≤ 20 in one trial and 36.8% in the other.

The treatment was generally well-tolerated, with no new safety concerns identified, although common side effects included upper respiratory infections and headaches, suggesting that long-term use of baricitinib can be safe and effective for managing severe alopecia areata.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Baricitinib in Patients with Severe Alopecia Areata over 52 Weeks of Continuous Therapy in Two Phase III Trials (BRAVE-AA1 and BRAVE-AA2). Kwon, O., Senna, MM., Sinclair, R., et al.[2023]

Oral tofacitinib and ruxolitinib show a 66% success rate in achieving significant improvement in alopecia areata, based on a systematic review of 12 studies involving 346 patients.

Common adverse events include infections and laboratory abnormalities, with a notable increase in lab issues for patients treated longer than six months, and a high recurrence rate of 74% within three months after stopping treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis. Yu, DA., Kim, YE., Kwon, O., et al.[2022]

A systematic review of 30 studies involving 289 cases found that 72.4% of patients with alopecia areata responded to JAK inhibitors, with a mean time to initial hair growth of about 2.2 months and complete regrowth in approximately 6.7 months.

Oral administration of JAK inhibitors was significantly more effective than topical treatments, and recurrences of hair loss were noted primarily after treatment was stopped, highlighting the need for ongoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors for alopecia areata: a systematic review and meta-analysis. Phan, K., Sebaratnam, DF.[2019]

A systematic review of 28 studies involving 1719 patients found that JAK-inhibitors for alopecia areata are generally well-tolerated, with most adverse events being mild and a low withdrawal rate due to side effects (1.6% compared to 2.2% for placebo).

Common adverse events included laboratory abnormalities (40.1%), respiratory issues (20.8%), and skin reactions (17.2%), but no fatal outcomes were reported, indicating a favorable safety profile for these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in patients treated with Jak-inhibitors for alopecia areata: A systematic review. Sechi, A., Song, J., Dell'Antonia, M., et al.[2023]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

Oral JAK inhibitors have shown a significantly higher response rate in treating alopecia areata compared to control groups, with a response rate of 6.86 times greater in randomized controlled trials involving 1845 patients.

Topical and sublingual JAK inhibitors were found to be ineffective, and there is a high recurrence rate of 54% after stopping treatment, suggesting that continuous administration may be necessary to maintain benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. Yan, D., Fan, H., Chen, M., et al.[2022]

JAK inhibitors represent a significant advancement in the treatment of moderate-to-severe alopecia areata (AA), a condition that previously had limited treatment options.

Phase 3 clinical trial data supports the efficacy of JAK inhibitors in treating AA, highlighting the importance of understanding the differences among various JAK inhibitors for optimal patient selection and safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus kinase inhibitors for alopecia areata. King, BA., Craiglow, BG.[2023]

In a long-term study involving two patients with alopecia areata, oral ruxolitinib led to sustained, near-complete hair regrowth over a year without any significant side effects.

The results suggest that ruxolitinib is a safe and effective treatment option for individuals with alopecia who do not respond to other therapies, warranting its consideration in community dermatology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring. Vandiver, A., Girardi, N., Alhariri, J., et al.[2021]

References

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

Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. [2023]

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

The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells. [2021]

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

Efficacy and Safety of Baricitinib in Patients with Severe Alopecia Areata over 52 Weeks of Continuous Therapy in Two Phase III Trials (BRAVE-AA1 and BRAVE-AA2). [2023]

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

Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

JAK inhibitors for alopecia areata: a systematic review and meta-analysis. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events in patients treated with Jak-inhibitors for alopecia areata: A systematic review. [2023]

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

Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. [2022]

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

Janus kinase inhibitors for alopecia areata. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring. [2021]