## Protocol Section
### Identification Module
**NCT ID:** NCT03800979

**Brief Title:** Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata

**Official Title:** Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata

#### Organization Study ID Info
**ID:** IRB/IEB 004/2562
#### Organization
**Class:** OTHER_GOV
**Full Name:** Institute of Dermatology, Thailand
### Status Module
#### Completion Date
**Date:** 2021-01-30

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-03-31

**Type:** ACTUAL

**Last Update Submit Date:** 2022-03-28

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2021-01-30

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2022-03-10

**Type:** ACTUAL

**Results First Submit Date:** 2022-01-23

**Results First Submit QC Date:** 2022-02-15

#### Start Date
**Date:** 2019-01-12

**Type:** ACTUAL

**Status Verified Date:** 2022-03

#### Study First Post Date
**Date:** 2019-01-11
**Type:** ACTUAL
**Study First Submit Date:** 2019-01-09
**Study First Submit QC Date:** 2019-01-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER_GOV

**Name:** Institute of Dermatology, Thailand

#### Responsible Party

**Investigator Affiliation:** Institute of Dermatology, Thailand

**Investigator Full Name:** Chinmanat Lekhavat

**Investigator Title:** Assistant Director of Institute of Dermatology

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The objective of this study is to assess the safety and efficacy of Tofacitinib in treating patients with extensive and recalcitrant Alopecia Areata (AA), along with to evaluate the economic impact of the patients that may be from changing in their quality of life. There are patients with severe AA who may have little or no improvement from the treatment by diphenylcyclopropenone (DPCP) or topical steroid with minoxidil but instead having positive response from the treatment with Janus kinase(JAK) inhibitor such as Tofacitinib or Ruxolitinib. For the best of my knowledge, there was no previous study in using Tofacitinib to treat severe AA before in Thailand.

**Detailed Description:** Alopecia areata (AA) or spot baldness, is a condition in which hair falls off from areas of the body. It often happens on the scalp, causing a few bald spots and it may result in psychological stress even though people are generally healthy. AA is believed to be an autoimmune disease progressing from a breach in the immune privilege of the hair follicles that causes hair to fall out in small patches, it may remain unnoticeable until the patches eventually connect and then become noticeable. It can develop slowly, and also recur after years between occurrences.

By standard AA treatment guideline, DPCP is the first treatment protocol and may follow with anthralin or minoxidil. This oldy but goody treatment gives a good result of 75% in spotty hair loss and 25% in total baldness. The new invention of treatment has been introduced in the past 2 years by using JAK inhibitor, an oral medicine such as Tofacitinib and Ruxolitinib. This treatment gives a good outcome so far in this short period of time, 54-81.9% of patients had over 50% increase of hair grows over the original protocol. The theory is that JAK inhibitors would inhibit interferon-gamma and interleukin-15 signal between white blood cell and hair follicle which reducing the rate of destroying hair follicles.

The investigators propose the study to assess the safety and efficacy of Tofacitinib for extensive and recalcitrant AA and to evaluate the economic impact effecting the AA patients. Tofacitinib is an expensive medicine and needed to be taken up to 6 months to finish the course to have a best outcome so it is not a popular choice of AA treatment at present time unless it can show a promising result in recalcitrant AA.

### Conditions Module

**Conditions:**

- Alopecia Areata

**Keywords:**

- Alopecia areata

- Alopecia universalis

- Alopecia totalis

- Tofacitinib

- JAK inhibitor

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** This is a Cohort study which all recruited volunteers will receive Tofacitinib for total of 24 weeks. The 19 volunteers are mixed male and female Thais who suffer from severe AA over 50% of the entire scalp.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 19

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

**Intervention Names:**

- Drug: Tofacitinib

**Label:** Tofacitinib

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Tofacitinib

**Description:** Tofacitinib is an oral medicine in Janus kinase inhibitor 3 group which has been approved by FDA in treating Rheumatoid Arthritis. It has ability to inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the cause of hair loss.

**Name:** Tofacitinib

**Other Names:**

- Xeljanz

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.

**Measure:** Number of Responders vs Non-Responders Using SALT Score

**Time Frame:** 48 weeks

#### Secondary Outcomes

**Description:** Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.

**Measure:** Side Effects From Tofacitinib

**Time Frame:** 48 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Thai volunteers age between 18 and 60 years old.
* Volunteers must be patients who suffer from severe AA more than 50% of the entire scalp.
* Volunteers must be patients who are able to complete the monthly treatment at least in the first 6 months.

Exclusion Criteria:

* Patients who suffer from other hair diseases such as: Telogen effluvium, Trichotillomania, Tinea capitis
* Patients who have other diseases that can have an impact on hair loss or temporary hair loss condition with in 6 months prior to the study such as: thyroid problems, liver disease, malnutrition, hearth disease, neurological disease, gastrointestinal disorders, sexually transmitted disease, cancer, psychiatric disease.
* Patients with AA who received treatment with either steroid, Anthralin or DPCP application within 1 month before the selection or patients who had oral or injection from steroid or other medication for hair loss treatment within 3 months before the selection.
* Woman with pregnancy

**Maximum Age:** 60 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Bangkok

**Country:** Thailand

**Facility:** Institute of Dermatology

#### Overall Officials

**Official 1:**

**Affiliation:** Institute of Dermatology

**Name:** Chinmanat Lekhavat, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031.

**PMID:** 20115946

**Citation:** Tosti A, Iorizzo M, Botta GL, Milani M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7. doi: 10.1111/j.1468-3083.2006.01781.x.

**PMID:** 17062039

**Citation:** Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. 1995 Dec;133(6):914-8. doi: 10.1111/j.1365-2133.1995.tb06925.x.

**PMID:** 8547044

**Citation:** Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-28. doi: 10.1016/j.jaad.2016.09.007. Epub 2016 Nov 2.

**PMID:** 27816293

**Citation:** Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32. doi: 10.1016/j.jaad.2016.09.006. Epub 2016 Nov 2.

**PMID:** 27816292

**Citation:** Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of Alopecia Areata With Tofacitinib. JAMA Dermatol. 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001.

**PMID:** 28355451

**Citation:** Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014 Sep;20(9):989-90. doi: 10.1038/nm.3685.

**PMID:** 25198048

**Citation:** Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010 Feb;62(2):177-88, quiz 189-90. doi: 10.1016/j.jaad.2009.10.032.

**PMID:** 20115945

## Document Section

### Large Document Module

#### Large Docs

- Date: 2018-08-27

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 184845

- Type Abbrev: Prot_SAP

- Upload Date: 2022-01-23T10:02

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007039

- Term: Hypotrichosis

- ID: D000006201

- Term: Hair Diseases

- ID: D000012871

- Term: Skin Diseases

- ID: D000020763

- Term: Pathological Conditions, Anatomical

### Condition Browse Module - Browse Branches

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M3846

- Name: Alopecia

- Relevance: HIGH

- As Found: Alopecia

- ID: M3847

- Name: Alopecia Areata

- Relevance: HIGH

- As Found: Alopecia Areata

- ID: M10089

- Name: Hypotrichosis

- Relevance: LOW

- As Found: Unknown

- ID: M9293

- Name: Hair Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: T290

- Name: Alopecia Totalis

- Relevance: LOW

- As Found: Unknown

- ID: T291

- Name: Alopecia Universalis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000000505

- Term: Alopecia

- ID: D000000506

- Term: Alopecia Areata

### Intervention Browse Module - Ancestors

- ID: D000075242

- Term: Janus Kinase Inhibitors

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M258018

- Name: Tofacitinib

- Relevance: HIGH

- As Found: Voice

- ID: M10407

- Name: Interferons

- Relevance: LOW

- As Found: Unknown

- ID: M1474

- Name: Janus Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000479163

- Term: Tofacitinib

### Misc Info Module

#### Submission Tracking

##### First MCP Info

###### Post Date

- Date: 2022-02-16

- Type: ACTUAL

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Tofacitinib

**Deaths Num At Risk:** 19

**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.

**ID:** EG000

**Other Num Affected:** 9

**Other Num at Risk:** 19

**Serious Number Affected:** 1

**Serious Number At Risk:** 19

**Title:** Tofacitinib

**Frequency Threshold:** 5

#### Other Events

**Term:** Dyslipidemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Notes:** Dyslipidemia (mild)

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** 

**Term:** Upper respiratory tract infection

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Notes:** Upper respiratory tract infection such as common cold

**Organ System:** Infections and infestations

**Source Vocabulary:** 

**Term:** Myalgia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Notes:** Myalgia

**Organ System:** Musculoskeletal and connective tissue disorders

**Source Vocabulary:** 

**Term:** Acne

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Skin and subcutaneous tissue disorders

**Source Vocabulary:** 

**Term:** Weight gain

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** 

**Term:** Constipation

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** 

#### Serious Events

**Term:** Intestinal tuberculosis

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Notes:** Ileal tuberculosis

**Organ System:** Gastrointestinal disorders

##### Stats

**Group ID:** EG000

**Num Affected:** 1

**Num At Risk:** 19

**Num Events:** 1

**Time Frame:** Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 19

**Units:** Participants

### Group

**ID:** BG000

**Title:** Tofacitinib

**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Tofacitinib is the Janus kinase inhibitor, which FDA has approved for Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 8.75

**Value:** 32.68

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 12

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 7

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 19

**Class Title:** Asian

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 19

**Class Title:** Thailand

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 14.24

**Value:** 95.11

**Class Title:** 

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** NUMBER
**Title:** Race/Ethnicity, Customized
**Unit of Measure:** participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Region of Enrollment
**Unit of Measure:** Participants
### Measure 5
**Description:** Baseline SALT (Severity of Alopecia Tool) score is the percentage of hair loss. The total SALT score is measured 0-100%, with higher values representing greater hair loss.
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Baseline SALT score
**Unit of Measure:** score
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** chinmanat@hotmail.com
**Organization:** Institute of Dermatology
**Phone:** +660847607474
**Title:** Dr. Chinmanat Lekhavat (My old last name is Tangjaturonrusamee.)
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 9
**Title:** Responders (SALT score improved >=50%)
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 10
**Title:** Non-responders (SALT score improved < 50%)
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 9
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 6
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 1
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** 48 weeks
**Title:** Number of Responders vs Non-Responders Using SALT Score
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.
**ID:** OG000
**Title:** Tofacitinib
#### Outcome Measure 2
**Description:** Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.
**Parameter Type:** NUMBER
**Reporting Status:** POSTED
**Time Frame:** 48 weeks
**Title:** Side Effects From Tofacitinib
**Type:** SECONDARY
**Unit of Measure:** participants
##### Group
**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.
**ID:** OG000
**Title:** Tofacitinib
### Participant Flow Module
#### Group
**Description:** All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata.

Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss.
**ID:** FG000
**Title:** Tofacitinib
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 19
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 19
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
**Pre-Assignment Details:** Nineteen participants who met the inclusion criteria were enrolled and received 10 mg/day oral tofacitinib.
**Has Results:** True