Tofacitinib for Immune Skin Conditions in Down Syndrome

NCT04246372 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 19-1362R33AR077495
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

People with Down syndrome (DS) display widespread immune dysregulation, including several immune skin conditions. This study hypothesizes that pharmacological inhibition of the increased interferon (IFN) signaling seen in DS is safe and could improve associated skin conditions. The study evaluates the safety and efficacy treatment with Tofacitinib, an FDA-approved drug known to block IFN signaling, in adolescents and adults with DS and an autoimmune and/or autoinflammatory skin condition. Investigators will also measure the impact of interferon inhibition on a variety of molecular markers, as well as the cognitive abilities and quality of life of participants.

Conditions

Down Syndrome; Alopecia Areata; Atopic Dermatitis / Eczema; Hidradenitis Suppurativa; Vitiligo; Psoriasis

Keywords

Interferon; Autoimmunity; Down syndrome; Skin disorder; JAK inhibitor; Inflammation; JAK/STAT; Dermatology

Outcome Measures

Primary Outcomes (2)

• Number of Serious Adverse Events (SAE) Definitely Related to Tofacitinib Treatment.

  Safety as measured by the number of serious adverse events definitely related to tofacitinib treatment.

  Baseline to 16 weeks

• Change in Whole Blood Transcriptome Interferon (IFN) Score

  The Interferon Score is a composite molecular measure used to quantify activation of the interferon signaling pathway. Interferon Scores are calculated by summing standardized expression (i.e. (expression value - mean) / standard deviation) of a predefined panel of 16 interferon-stimulated genes, measured by RNA-sequencing of whole blood samples. The resulting composite value provides an integrated measure of interferon pathway activity, with higher scores indicating greater pathway activation. No clinical relevance threshold has been established.

  Baseline and 16 weeks

Secondary Outcomes (8)

• Change in Investigator's Global Assessment (IGA)

  Baseline and 16 weeks

• Change in Dermatology Life Quality Index (DLQI)

  Baseline and 16 weeks

• Change in Eczema Area and Severity Index (EASI) Score in Participants With Atopic Dermatitis

  Baseline and 16 weeks

• Change in Severity of Alopecia Tool (SALT) Score in Participants With Alopecia

  Baseline and 16 weeks

• Change in Modified Sartorius Score (MSS) Score in Participants With Hidradenitis Suppurativa

  Baseline and 16 weeks

Study Arms (1)

On Treatment

EXPERIMENTAL

Tofacitinib 5mg oral tablets twice daily for 16 weeks

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome

Also known as: Xeljanz

On Treatment

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males or females with DS between 12 and 50 years of age who weigh at least 40 kg.
• Diagnosis of at least one active immune skin condition, including but not limited to:
• Moderate-to-severe atopic dermatitis
• Alopecia areata affecting at least 25% of the scalp
• Moderate-to-severe hidradenitis suppurativa
• Moderate-to-severe psoriasis
• Moderate-to-severe vitiligo.
• Be willing to avoid pregnancy or fathering children.
• Must present with a study partner or legal guardian who can complete, or assist with completing, study materials as appropriate.

You may not qualify if:

• Weigh less than 40 kg.
• Pregnancy or breast feeding.
• No study partner or legal guardian.
• Clinically significant chronic or active viral infection including but not limited to HIV, hepatitis, CMV, EBV, HSV.
• Severe renal impairment.
• History of malignant solid tumor cancer within five years prior to study entry or where there is current evidence of recurrent or metastatic disease.
• Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements.
• Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment.
• Concomitant treatment with other immunosuppressants (e.g. corticosteroids, methotrexate) or strong CP3A4 or CYP2C19 inhibitors or inducers (e.g. ketoconazole, fluconazole).
• Known allergies, hypersensitivity, or intolerance to Tofacitinib.
• History of thrombotic disorder.
• History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
• Participants may be excluded for other unforeseen reasons at the study doctor's discretion.
• Unable to provide assent in cases where informed consent is obtained from other authorized representative.
• Kidney transplant within the last two years

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Linda Crnic Institute for Down Syndrome

Aurora, Colorado, 80045, United States

Location

Related Publications (4)

• Rachubinski AL, Estrada BE, Norris D, Dunnick CA, Boldrick JC, Espinosa JM. Janus kinase inhibition in Down syndrome: 2 cases of therapeutic benefit for alopecia areata. JAAD Case Rep. 2019 Apr 5;5(4):365-367. doi: 10.1016/j.jdcr.2019.02.007. eCollection 2019 Apr. No abstract available.

  PMID: 31008170 BACKGROUND

• Pham AT, Rachubinski AL, Enriquez-Estrada B, Worek K, Griffith M, Espinosa JM. JAK inhibition for treatment of psoriatic arthritis in Down syndrome. Rheumatology (Oxford). 2021 Sep 1;60(9):e309-e311. doi: 10.1093/rheumatology/keab203. No abstract available.

  PMID: 33630031 BACKGROUND

• Rachubinski AL, Wallace E, Gurnee E, Enriquez-Estrada BA, Worek KR, Smith KP, Araya P, Waugh KA, Granrath RE, Britton E, Lyford HR, Donovan MG, Eduthan NP, Hill AA, Martin B, Sullivan KD, Patel L, Fidler DJ, Galbraith MD, Dunnick CA, Norris DA, Espinosa JM. JAK inhibition decreases the autoimmune burden in Down syndrome. Elife. 2024 Dec 31;13:RP99323. doi: 10.7554/eLife.99323.

  PMID: 39737640 DERIVED

• Rachubinski AL, Wallace E, Gurnee E, Estrada BAE, Worek KR, Smith KP, Araya P, Waugh KA, Granrath RE, Britton E, Lyford HR, Donovan MG, Eduthan NP, Hill AA, Martin B, Sullivan KD, Patel L, Fidler DJ, Galbraith MD, Dunnick CA, Norris DA, Espinosa JM. JAK inhibition decreases the autoimmune burden in Down syndrome. medRxiv [Preprint]. 2024 Oct 16:2024.06.13.24308783. doi: 10.1101/2024.06.13.24308783.

  PMID: 38946973 DERIVED

Related Links

• The Crnic Institute Human Trisome Project

MeSH Terms

Conditions

Down Syndrome; Alopecia Areata; Dermatitis, Atopic; Eczema; Hidradenitis Suppurativa; Vitiligo; Psoriasis; Autoimmune Diseases; Skin Diseases; Inflammation

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Alopecia; Hypotrichosis; Hair Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Genetic; Dermatitis; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Hidradenitis; Sweat Gland Diseases; Hypopigmentation; Pigmentation Disorders; Skin Diseases, Papulosquamous; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Joaquin Espinosa
• Organization: Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz

joaquin.espinosa@cuanschutz.edu

303-724-7389

Study Officials

• Joaquin Espinosa, PhD

  Linda Crnic Institute, University of Colorado Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will receive the investigational product, Tofacitinib.

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: January 29, 2020
• Study Start: October 21, 2020
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: December 11, 2025
• Results First Posted: December 11, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be made available upon publication in a peer-reviewed journal.
• Access Criteria: Data access requests will be reviewed by the sponsor-investigator and collaborators.

Locations

US (1)