Down SyndromePhase 2NCT04246372
Tofacitinib for Immune Skin Conditions in Down Syndrome
A Phase 2 study testing Tofacitinib in people with Down Syndrome and Alopecia Areata, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 50 years
- Conditions the study is for
- Down Syndrome, Alopecia Areata, Atopic Dermatitis / Eczema
- What is being tested?
- Tofacitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2020to 30 Oct 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- Weigh less than 40 kg.
- Pregnancy or breast feeding.
- No study partner or legal guardian.
- Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study.
- Clinically significant chronic or active viral infection including but not limited to HIV, hepatitis, CMV, EBV, HSV.
- Severe renal impairment.
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- 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.
- Superficial skin infection within 2 weeks of inclusion in the study.
- History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
- Intravenous antimicrobial therapy within 3 months of inclusion in the study.
- Oral antimicrobials within 2 weeks of inclusion in the study.
- 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
- Any history of heart attack or stroke.
- Any history of lymphoma.
- Past or current smokers.
Trial locations and contacts
1 site in 1 country.
United States1 site
Linda Crnic Institute for Down Syndrome
Aurora, Colorado, 80045
About this study
Official title: Safety and Efficacy of Tofacitinib for Immune Skin Conditions in Down Syndrome
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.
Read the detailed description
Trisomy 21 (T21) is the most common human chromosomal disorder, occurring in ~1/700 live births, leading to the condition known as Down syndrome (DS). Importantly, people with DS display widespread immune dysregulation and over half of adults with T21 are affected by one or more autoimmune conditions, including several immune skin conditions. The driving hypothesis for this study is that hyperactivation of interferon (IFN) signaling leads to myriad immune-driven diseases and immunological phenotypes in people with DS, and that pharmacological inhibition of IFN signaling could have multidimensional therapeutic benefits in this population.
This study utilizes Tofacitinib, an FDA-approved drug known to block IFN signaling and several accompanying inflammatory pathways, to reduce IFN signaling in DS and to measure its effects via multidimensional endpoints. Previous studies and current clinical trials indicate that Janus kinase (JAK) inhibitors, such as Tofacitinib, can block inflammatory pathways and may have beneficial effects on immune skin conditions. Further, inhibition of chronically active IFN signaling in DS with Tofacitinib may attenuate other core drivers of immune dysregulation, leading to improvements in other immune diseases and conditions common to DS that are potentially driven by inflammation, such as cognitive deficits. Investigators will test these hypotheses using a battery of immune and molecular assessments, as well as cognitive testing and quality of life measures. This clinical trial evaluates adolescent and adult participants with DS during eight study visits over an approximate five month period.
Specific Aims:
- To define the safety profile of JAK inhibition in people with DS,
- To determine the impact of JAK inhibition on the immune dysregulation caused by trisomy 21,
- To define the impact of JAK inhibition on immune skin conditions in DS, and
- To characterize the impact of JAK inhibition on cognition and quality of life in DS.
- Conditions
- Down Syndrome, Alopecia Areata, Atopic Dermatitis / Eczema, Hidradenitis Suppurativa, Vitiligo, Psoriasis
- Being tested
- Tofacitinib
- Keywords
- Interferon, Autoimmunity, Down syndrome, Skin disorder, JAK inhibitor, Inflammation, JAK/STAT, Dermatology
- Medical subject headings
- Down Syndrome, Alopecia Areata, Dermatitis, Atopic, Eczema, Hidradenitis Suppurativa, Vitiligo, Psoriasis, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofacitinibDrug
Also called Xeljanz
Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
| Study group | Role | What they receive |
|---|---|---|
| On Treatment | Experimental | Tofacitinib 5mg oral tablets twice daily for 16 weeks Receives: Drug: Tofacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and 16 weeks
Secondary outcomes (8)
Change in Investigator's Global Assessment (IGA)
The IGA is used to assess overall changes in severity across five skin conditions (alopecia areata, atopic dermatitis, vitiligo, psoriasis and hidradenitis suppurativa) scored from 0 (clear) to 4 - 5 (very severe).
Measured: Baseline and 16 weeks
Change in Dermatology Life Quality Index (DLQI)
The DLQI is used to assess participant-reported impact of skin conditions on self-image, relationships, and daily activities. Possible total scores range from 0-30, with higher scores indicating a more impaired quality of life.
Measured: Baseline and 16 weeks
Change in Eczema Area and Severity Index (EASI) Score in Participants With Atopic Dermatitis
The EASI is used to assess changes in the extent (area) and severity of atopic dermatitis (eczema). Each of four sites (head, upper limbs, trunk, and lower limbs), are weighted by overall contribution to body surface area and separately scored by using four parameters (erythema, infiltration, excoriations, lichenification), each of which is graded on a severity scale of 0 (none) to 4 (severe), as well as degree of involvement. Possible total scores range from 0-72, with higher scores indicating a more severe involvement.
Measured: Baseline and 16 weeks
Change in Severity of Alopecia Tool (SALT) Score in Participants With Alopecia
The SALT is used to assess changes in degree and extent (area) of hair loss due to alopecia areata on the head. Each of four scalp sites (left side, right side, top and back) are weighted by overall contribution to scalp surface area and rated for percent involvement. Possible total scores range from 0-72, with higher scores indicating a larger affected area.
Measured: Baseline and 16 weeks
Change in Modified Sartorius Score (MSS) Score in Participants With Hidradenitis Suppurativa
The MSS is used to assess changes in areas affected by hidradenitis suppurativa. Each of seven sites (right/left axillae, right/left groin, right/left gluteal, other) are scored by number of lesions, distance between lesions, and presence of normal skin between lesions. Possible total scores range up from 0 with no maximum, with higher scores indicating a more severe involvement.
Measured: Baseline and 16 weeks
Change in Psoriasis Area and Severity Index (PASI) Score in Participants With Psoriasis
The PASI is used to assess changes in extent (area) and severity of psoriasis. Each of four sites (head, upper limbs, trunk, and lower limbs) are weighted by overall contribution to body surface area and separately scored by degree of involvement and three additional parameters (erythema, induration and desquamation), each of which is graded on a severity scale of 0 (Not severe) to 4 (very severe). Possible total scores range from 0-72, with higher scores indicating a more severe involvement.
Measured: Baseline and 16 weeks
Change in Vitiligo Extent Tensity Index (VETI) in Participants With Vitiligo
The VETI is used to assess changes in extent (area) of skin affected by vitiligo. Each of five sites (head, trunk, upper limbs, lower limbs, genitalia) are weighted by overall contribution to body surface area and rated for degree of de-pigmentation scale of Stage 0 (normal skin) to Stage 5 (complete de-pigmentation plus significant hair whitening) and percent involvement. Possible scores range from 0-55.5, with a higher score indicating a higher degree of involvement.
Measured: Baseline and 16 weeks
A Composite Cytokine Score Generated Using the Meso Scale Discovery (MSD) Platform Used to Assess Inflammatory Changes in Plasma.
The Cytokine Score is a composite molecular measure used to quantify inflammatory changes. Cytokine Scores are calculated by summing standardized abundance (i.e. (abundance value - mean) / standard deviation) of a predefined panel of four inflammatory cytokines, measured in plasma samples using the Meso Scale Discovery platform. The resulting composite value provides an integrated measure of inflammatory activity, with higher scores indicating a more inflammatory state. No clinical relevance threshold has been established.
Measured: Baseline and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2020
- Study start21 Oct 2020
- Primary completion30 Oct 2024
- Study completion30 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants will receive the investigational product, Tofacitinib.
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Joaquin Espinosa, PhD, Principal investigator, Linda Crnic Institute, University of Colorado Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04246372
- Sponsor's protocol ID
- 19-1362
- Other IDs
- R33AR077495
- Status last verified
- Nov 2025
- First submitted
- 27 Jan 2020
- Last updated
- 11 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data will be made available for all primary outcome measures.
Publications
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.
PubMed 31008170Pham 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.
PubMed 33630031Rachubinski 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.
PubMed 39737640Rachubinski 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.
PubMed 38946973