Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis (SCLERITA)

March 27, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis: a Phase II, Randomized, Controlled Trial

The purpose of this study is to determine whether itacitinib is safe and effective in the treatment of systemic sclerosis in adults.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Systemic sclerosis (SSc) is a rare systemic autoimmune connective tissue-disease characterized by fibrosis, inflammation, and vasculopathy. SSc is responsible for skin fibrosis that can either be limited or diffuse. The latter phenotype of the disease is commonly associated with visceral involvement and therefore similar to graft versus host disease (GvHD) reaction. It can be life threatening in case of pulmonary or cardiovascular involvement. Nonetheless SSc remains a severe disease responsible for important disability and a poor quality of life.

There is a growing body of evidence that supports the implication of the JAK-STAT tyrosine kinases pathway in the activation of fibroblasts of patients with SSc. A genetic polymorphism of STAT4 was found to be associated with the diffuse form of the disease and inhibition of STAT4 gene is associated with a decrease in TGF-ß and IL-6 cytokines activation, which are two major cytokines implicated in SSc pathogenesis. Recently, Pedroza et al. confirmed the implication of STAT3 in skin fibrosis mechanisms. Indeed, the authors showed an enhanced activation of STAT3 and demonstrated in vivo that the inhibition of STAT3 phosphorylation prevented skin fibrosis in a murine model of SSc. These data were confirmed by a work of Zhang et al. who showed that the inhibition of JAK1 was also needed to prevent skin and lung fibrosis. Altogether these works confirmed the implication of the JAK pathway in fibrosis mechanism.

Itacitinib is a Janus kinase inhibitor that specifically targets JAK1 and decreases STAT3 phosphorylation. Itacitinib was shown to efficiently treat patients with myelofibrosis, rheumatoid arthritis, and chronic plaque psoriasis. Very interestingly, itacitinib efficacy has also been reported in patients with acute GvHD. Altogether these data and studies reinforced the investigator's working hypothesis.

The efficacy and safety of this proposal must be tested.

Study Type

Interventional

Enrollment (Anticipated)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80000
        • Recruiting
        • CH Amiens
      • Angers, France, 49100
        • Recruiting
        • CHU Angers
      • Annecy, France, 74370
        • Recruiting
        • CHU Annecy
      • Bobigny, France, 93022
        • Recruiting
        • Avicenne Hospital
      • Bordeaux, France, 33000
        • Recruiting
        • Chu Bordeaux
      • Boulogne-Billancourt, France, 92100
        • Recruiting
        • Ambroise Paré Hospital
      • Caen, France, 14000
        • Recruiting
        • CHU Caen
      • Clermont-Ferrand, France, 63000
        • Recruiting
        • CHU Gabriel Montpied
      • Créteil, France, 94000
        • Recruiting
        • Henry Mondor hospital
      • Dijon, France, 21000
        • Recruiting
        • CHU Dijon
      • Grenoble, France, 38700
        • Recruiting
        • CHU Grenoble
      • Lille, France, 59000
        • Recruiting
        • CHU Lille
      • Limoges, France, 87000
        • Recruiting
        • CHU Limoges
      • Lyon, France, 69310
        • Recruiting
        • CHU Lyon Sud
      • Marseille, France, 13015
        • Recruiting
        • Hôpital Nord
      • Marseille, France, 13385
        • Recruiting
        • La Timone Hospital
      • Montpellier, France, 34090
        • Recruiting
        • CHU Montpellier - rhumatology
      • Montpellier, France, 34090
        • Recruiting
        • CHU Montpellier - St Eloi Hospital
      • Nancy, France, 54035
        • Recruiting
        • CHU Nancy
      • Nantes, France, 44093
        • Recruiting
        • CHU Nantes
      • Nice, France, 06000
        • Recruiting
        • Hospital Pasteur - CHU Nice
      • Paris, France, 75014
        • Recruiting
        • Cochin Hospital
      • Paris, France, 75012
        • Not yet recruiting
        • Saint Antoine Hospital
      • Paris, France, 75020
        • Not yet recruiting
        • Hospital Croix St Simon
      • Poitiers, France, 86021
        • Recruiting
        • CHU Poitiers
      • Reims, France, 51100
        • Recruiting
        • Robert Debre Hospital
      • Rennes, France, 35200
        • Recruiting
        • Hopital Sud
      • Rouen, France, 76000
        • Not yet recruiting
        • CHU Rouen
      • Strasbourg, France, 67000
        • Recruiting
        • Nouvel Hospital Civil
      • Toulouse, France, 31400
        • Recruiting
        • Rangueil hospital
      • Tours, France, 37000
        • Recruiting
        • CHU Tours
      • Valenciennes, France, 59300
        • Recruiting
        • CH Valenciennes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patient (≥18 years old)
  • Patient with a diagnosis of diffuse SSc, as defined by the American College of Rheumatology / EULAR 2013 criteria,
  • Patient with a SSc disease duration of less than 36 months (defined as time from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined by EUSTAR disease activity score,
  • Patient with a modified Rodnan skin score (mRSS) ≥ 10 and ≤ 35 units at screening,
  • Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception for the 12 months' duration of the study,
  • Patient able to give written informed consent prior to participation in the study,
  • Affiliation to a social security scheme (profit or being entitled).

Exclusion Criteria:

  • Previous treatment with itacitinib or a Janus kinase (JAK) inhibitor,
  • Contra-indications to itacitinib or Janus kinase inhibitor,
  • Failure to sign the informed consent or unable to consent
  • Patient participating in another investigational therapeutic study,
  • Current, or history of recurrent infections, including HBV, HCV, HIV,
  • Patient with other uncontrolled diseases, including drug or alcohol abuse, severe psychiatric diseases, that could interfere with participation in the trial according to the protocol,
  • Patient suspected not to be observant to the proposed treatments,
  • Patient who have white blood cell count ≤ 4,000/mm3,
  • Patient who have platelet count ≤ 100,000/mm3,
  • Patients who have ALT or AST level greater that 3 times the upper limit of normal,
  • Patient who have triglyceride level greater than 5g/L
  • Pregnant or breastfeeding woman,
  • Protected adults (including individual under guardianship by court order),
  • Patient receiving or having received mycophenolate mofetil or methotrexate within the last month (possible inclusion beyond one month),
  • Patient receiving or having received cyclophosphamide or rituximab within the last three months (possible inclusion beyond 3 months),
  • Patient receiving or having received a biotherapy (anti-TNF, abatacept or tocilizumab) in the last 3 months (possible inclusion beyond 3 months)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Itacitinib
200mg of oral Itacitinib everyday for 360 days.
Drug: Itacitinib
200 mg oral for 360 days
Placebo Comparator: Placebo
Oral placebo everyday for 360 days.
Drug: Placebo
200 mg oral for 360 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in modified Rodnan skin score (mRSS) at 360 days
Time Frame: 360 days

performed by the same investigator at day 0 and day 360 and the change in mRSS will be calculated following the formula: ΔmRSS= mRSSd360 - mRSSd0.

To measure mRSS, skin thickness of the patient is rated by palpation at each of 17 anatomic sites using a scale of 0-3 (0 = normal skin; 1= mild thickness; 2= moderate thickness; 3=severe thickness with an inability to pinch the skin into a fold). The scores at each site are summed with a minimum of 0 and a maximum of 51 (17 sites)
360 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of death
Time Frame: at 180 and 360 days
at 180 and 360 days
Incidence of Adverse Events
Time Frame: at 180 and 360 days
according to the Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading scale
at 180 and 360 days
Incidence of Severe Adverse Events
Time Frame: at 180 and 360 days
according to the Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading scale
at 180 and 360 days
Change in modified Rodnan skin score at 90, 180, 270 days
Time Frame: at 90, 180 and 270 days
at 90, 180 and 270 days
Proportion of patients who improved mRSS at 90, 180, 270 and 360 days
Time Frame: At 90, 180, 270 and 360 days
At 90, 180, 270 and 360 days
Proportion of patients with an active disease according to the European scleroderma trials and research group (EUSTAR)SSc activity score at 90, 180, 270 and 360 days
Time Frame: At 90, 180, 270 and 360 days
EUSTAR SSc activity index score from 0 to 10 - a cut-off ≥ 2.5 identifies patients with active disease
At 90, 180, 270 and 360 days
Change in the Combined Response Index in Diffuse Systemic Sclerosis (CRISS) score
Time Frame: At 180 and 360 days
composite response index
At 180 and 360 days
SSc disease activity
Time Frame: At 90, 180, 270 and 360 days
  • Physicians visual analogue scale range from 0 (min) to 10 (max) - 0=no activity, 10=maximum activity
  • Patients visual analogue scale range from 0 (min) to 10 (max) - 0=no activity, 10=maximum activity
At 90, 180, 270 and 360 days
Short Form-36 (SF-36) health questionnaire
Time Frame: At 0, 15, 90, 180, 270 and 360 days
self-administered questionnaire of 36 items assessing the following 8 domains : physical functioning, bodily pain, role limitations attributable to physical health problems, general health perceptions, mental health, role limitations to emotional problems, vitality and social functioning (scale from 0 to 100)
At 0, 15, 90, 180, 270 and 360 days
EurolQol-5Domain (EQ-5D) health questionnaire
Time Frame: At 0, 15, 90, 180, 270 and 360 days
self reported measure of quality of life - (scale from 0 to 100)
At 0, 15, 90, 180, 270 and 360 days
Health Assessment Questionnaire Disability Index (HAQ-DI) scale
Time Frame: At 0, 15, 90, 180, 270 and 360 days
self administered 20 questions- score range from 0 (no disability) to 3 (severe disability)
At 0, 15, 90, 180, 270 and 360 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2023

Primary Completion (Anticipated)

February 1, 2026

Study Completion (Anticipated)

February 1, 2026

Study Registration Dates

First Submitted

February 10, 2021

First Submitted That Met QC Criteria

March 8, 2021

First Posted (Actual)

March 10, 2021

Study Record Updates

Last Update Posted (Actual)

March 28, 2023

Last Update Submitted That Met QC Criteria

March 27, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P180613
  • 2019-003430-16 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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