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Trial record 66 of 184 for:    trisomy21 NOT prenatal

Tofacitinib in Down Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04246372
Recruitment Status : Not yet recruiting
First Posted : January 29, 2020
Last Update Posted : January 29, 2020
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
University of Colorado, Denver

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 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.


Condition or disease Intervention/treatment Phase
Down Syndrome Alopecia Atopic Dermatitis/Eczema Hidradenitis Suppurativa Vitiligo Psoriasis Drug: Tofacitinib Phase 2

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 adult participants with DS during eight study visits over an approximate five month period.

Specific Aims:

  1. To define the safety profile of JAK inhibition in people with DS,
  2. To determine the impact of JAK inhibition on the immune dysregulation caused by trisomy 21,
  3. To define the impact of JAK inhibition on immune skin conditions in DS, and
  4. To characterize the impact of JAK inhibition on cognition and quality of life in DS.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Intervention Model: Single Group Assignment
Intervention Model Description: All participants will receive the investigational product, Tofacitinib.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Tofacitinib for Immune Skin Conditions in Down Syndrome
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: On Treatment
Tofacitinib 5mg oral tablets twice daily for 16 weeks
Drug: Tofacitinib
Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome
Other Name: Xeljanz




Primary Outcome Measures :
  1. Safety as Assessed by Number of Serious Adverse Events (SAE) [ Time Frame: Up to Week 18 ]
    Number of SAEs that are definitely attributable to Tofacitinib

  2. Change in Interferon (IFN) Scores in the Transcriptome of White Blood Cells [ Time Frame: Baseline and 16 weeks ]
    A composite score used to represent the change in activation of the interferon pathway. Possible scores increase from zero with higher scores indicating a more activated interferon pathway.


Secondary Outcome Measures :
  1. Change in Investigator's Global Assessment (IGA) [ Time Frame: Baseline and 16 weeks ]
    The IGA will be used to assess overall changes in severity across five skin diseases (alopecia, atopic dermatitis, vitiligo, psoriasis and hidradenitis suppurativa) scored from 0 (no involvement) to 4 (severe).

  2. Change in Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline and 16 weeks ]
    The DLQI will be 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.

  3. Change in Eczema Area and Severity Index (EASI) Score in Participants with Atopic Dermatitis [ Time Frame: Baseline and 16 weeks ]
    The EASI will be 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.

  4. Change in Severity of Alopecia Tool (SALT) Score in Participants with Alopecia [ Time Frame: Baseline and 16 weeks ]
    The SALT will be used to assess changes in degree and extent (area) of hair loss due to alopecia 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.

  5. Change in Modified Sartorius Score (MSS) Score in Participants with Hidradenitis Suppurativa [ Time Frame: Baseline and 16 weeks ]
    The MSS will be 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.

  6. Change in Psoriasis Area and Severity Index (PASI) Score in Participants with Psoriasis [ Time Frame: Baseline and 16 weeks ]
    The PASI will be 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.

  7. Change in Vitiligo Extent Tensity Index (VETI) in Participants with Vitiligo [ Time Frame: Baseline and 16 weeks ]
    The VETI will be 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.

  8. A composite score generated using the Meso Scale Discovery (MSD) platform used to assess inflammatory changes in plasma. [ Time Frame: Baseline and 16 weeks ]
    Possible total scores increase from zero, with higher scores indicating a higher inflammatory state.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults with Down syndrome between 18 and 40 years of age.
  • A cytogenetic diagnosis of full T21 or complete unbalanced translocation of chromosome 21.
  • Diagnosis of at least one active immune skin condition, including but not limited to 1) moderate-to-severe atopic dermatitis, 2) any type of alopecia affecting at least 25% of the scalp, 3) moderate-to-severe hidradenitis suppurativa, 4) moderate-to-severe psoriasis, 5) 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.

Exclusion Criteria:

  • 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 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 4 weeks of inclusion in the study.
  • Participants may be excluded for other unforeseen reasons at the study doctor's discretion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04246372


Contacts
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Contact: Angela Rachubinski, PhD 303-724-7366 DSresearch@ucdenver.edu
Contact: Belinda Enriquez Estrada, MS 303-724-0491 DSresearch@ucdenver.edu

Locations
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United States, Colorado
Linda Crnic Institute for Down Syndrome
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Principal Investigator: Joaquin Espinosa, PhD Linda Crnic Institute, University of Colorado Anschutz Medical Campus
Principal Investigator: Cory Dunnick, MD Department of Dermatology, University of Colorado Anschutz Medical Campus
Principal Investigator: David Norris, MD Department of Dermatology, University of Colorado Anschutz Medical Campus

Additional Information:
Publications:
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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT04246372    
Other Study ID Numbers: 19-1362
R61AR077495 ( U.S. NIH Grant/Contract )
First Posted: January 29, 2020    Key Record Dates
Last Update Posted: January 29, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data will be made available for all primary outcome measures.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Colorado, Denver:
Interferon
Autoimmunity
Down syndrome
Skin disorder
JAK inhibitor
Inflammation
JAK/STAT
Dermatology
Additional relevant MeSH terms:
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Down Syndrome
Hidradenitis Suppurativa
Dermatitis, Atopic
Psoriasis
Dermatitis
Alopecia
Vitiligo
Hidradenitis
Syndrome
Disease
Pathologic Processes
Skin Diseases, Papulosquamous
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hypotrichosis
Hair Diseases
Pathological Conditions, Anatomical
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Hypopigmentation