Abatacept in Juvenile Dermatomyositis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 April 2022
• Main ID: NCT02594735
• Date of registration: 21/10/2015
• Prospective Registration: Yes
• Primary sponsor: George Washington University
• Public title: Abatacept in Juvenile Dermatomyositis AID
• Scientific title: Abatacept for the Treatment of Refractory Juvenile Dermatomyositis
• Date of first enrolment: November 2015
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02594735
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Rodolfo V Curiel, MD
• Affiliation: The George Washington University

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adults with definite or probable JDM and pediatric patients 7 years of age and older
with definite or probable JDM.

2. Body weight of at least 25 kg (or at least 55 lbs) and age = 7 years of age.

3. Patients must reside within the United States or Canada.

4. Refractory myositis, as defined by the intolerance to or an inadequate response to
corticosteroids plus an adequate regimen of at least one other immunosuppressive
agent, including azathioprine, methotrexate, IVIG, mycophenolate mofetil,
cyclophosphamide, tacrolimus or cyclosporine A, or a biologic therapy. The definition
of intolerance is: side effects that require discontinuation of the medication or an
underlying condition that precludes the further use of the medication.

5. At least moderately active disease as documented by:

- MD global VAS with a minimum value of 2.5 cm on a 10 cm scale AND

- At least 2 other abnormal core set measures listed below:

6. Therapy with prednisone or another glucocorticoid is required, unless there is
documented intolerance in the medical record or a medical condition that
contraindicates further use of prednisone. The prednisone dose must be stable for at
least 4 weeks prior to the screening visit.

7. Background therapy with at least 1 non-corticosteroid immunosuppressive agent is
required at a stable dose for at least 6 weeks prior to the screening visit unless
there is documentation that the patient is intolerant, which is defined as side
effects that require discontinuation of the medication(s) or an underlying condition
that precludes the further use of the IS medication.

8. If an immunosuppressive agent was discontinued prior to the screening visit then there
must be a:

- 4 week washout for prednisone or methotrexate

- 8 week washout for any other IS agent

- For discontinuation of biologic therapies, a washout of 5 terminal half lives

9. If on hydroxychloroquine or colchicine, the dose should be stable for 6 weeks prior to
Visit 1.

10. If on statin or fibric acid derivative agents, the dose should be stable for 6 weeks
prior to Visit 1.

11. Ability of patient or parent to complete self-report questionnaires.

12. Men and women of reproductive potential must agree to use a reliable method of birth
control during the 24 week duration of the trial described in the reproductive risks
section of this protocol (section 4.3). They must also agree to use a reliable method
of birth control for 100 days after the last dose of study drug is administered.

13. Patients must agree to forgo immunization with a live vaccine during the course of the
study or within 3 months after discontinuation.

14. Patients must have a letter from the referring rheumatologist or specialist
supervising the care of the JDM, agreeing to the patient's participation in the study
and to continuing to provide care for the patient, including emergency care during the
trial.

Core Set Measures:

- An MMT-8 score that is no greater than 125/150

- Patient/Parent Global VAS with a minimum value of 2.0 cm on a 10cm scale

- CHAQ/HAQ disability index with a minimum value of 0.25

- Elevation of at least one of the muscle enzymes [which includes creatine kinase (CK),
aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate
aminotransferase (AST)] at a minimum level of 1.3 x the upper limit of normal.

- Global extra-muscular disease activity score with a minimum value of 2.0 cm on a 10 cm
VAS scale

Exclusion Criteria:

1. Drug-induced myositis (myositis in patients taking medications known to induce
myositis-like syndromes, including, but not limited to, statin agents, fibric acid
derivatives, and colchicine).

2. Juvenile polymyositis; inclusion body myositis; cancer-associated myositis, defined as
the diagnosis of myositis within 2 years of the diagnosis of cancer except basal or
squamous cell skin cancer or carcinoma in situ of the cervix if at least 5 years since
excision

3. Myositis in overlap with another connective tissue disease (CTD) that precludes the
accurate assessment of a treatment response (for example, difficulty in assessing
muscle strength in a scleroderma patient with associated myositis)

4. History of receiving a live vaccine 4 weeks prior to initiation of study treatment

5. Joint disease, severe calcinosis, or other musculoskeletal condition, which precludes
the ability to quantitate muscle strength.

6. Wheelchair bound patients.

7. Known hypersensitivity to abatacept or prior receipt of abatacept

8. Concomitant illness that would prevent adequate patient assessment or in the
investigators opinion pose an added risk for study participants:

9. Recurrent or chronic infections, including HIV, tuberculosis, hepatitis B and C, or TB
infection, including contact with a household contact with active tuberculosis (TB)
and who did not receive appropriate and documented prophylaxis for TB. (a documented
negative Hepatitis B surface antigen and Hepatitis C antibody completed at the
screening visit or within 6 weeks prior to screening visit is required)

10. Have had symptomatic herpes zoster or herpes simplex infection (not including simple
oral HSV lesions) within 12 weeks prior to entry or during screening period

11. Have a history of disseminated/complicated herpes zoster (for example,
multi-dermatomal involvement, ophthalmic zoster, central nervous system (CNS)
involvement, post-herpetic neuralgia)

12. Known liver disease (i.e. cirrhosis or other conditions compromising the synthetic
function of the liver)

13. Disorders that would preclude accurate assessment of neuromuscular function

14. Cardiomyopathy or arrhythmias that in the investigators opinion poses an additional
risk for study participants

15. New York Heart Association Classification III or IV for congestive heart failure

16. Psychiatric illness that precludes compliance or neuromuscular assessment

17. Serum creatinine > 2.0mg/dl

18. Pregnant females or nursing mothers

19. Life threatening illness that would interfere with the patient's ability to complete
the study.

20. Known or suspected history of drug or alcohol abuse within the past 6 months as
determined by the medical record or patient interview

21. Anticipated poor compliance

22. Participation in another clinical experimental therapeutic stud


Age minimum: 7 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Dermatomyositis

Intervention(s)

Drug: Abatacept

Primary Outcome(s)

Incidence of treatment-emergent adverse events. [Time Frame: week 0 to week 24]

Number of patients meeting the definition of improvement (DOI) at week 24: at least 3 of 6 Core Set Measures (CSM) improved by = 20% with no more than 2 CSM worsening by = 25% (not including the manual muscle testing). [Time Frame: week 0 to week 24]

Secondary Outcome(s)

Number of patient developing HAHA (human anti-human) antibodies [Time Frame: week 0 to week 24]

Number of patients with changes in biomarkers of disease activity [Time Frame: week 0 to 24]

Number of patients with improvement in physical function from baseline [Time Frame: week 0 to 24]

Number of patient with improvement in muscle inflammation from baseline [Time Frame: week 0 to week 24]

Number of patients with improvement in extra-muscular activity from baseline [Time Frame: week 0 to 24]

Number of patient with improvement in cutaneous activity disease from baseline [Time Frame: week 0 to week 24]

Number of patients improving in Physician and Patient/Parent global activity measurement from baseline [Time Frame: week 0 to week 24]

Number of patient with improvement in Muscle strength [Time Frame: week 0 to week 24]

Number of patients with improvement is muscle enzymes from baseline [Time Frame: week 0 to 24]

Number of patients with steroid-sparing benefit from baseline [Time Frame: week 0 to week 24]

Secondary ID(s)

IRB 111418

Source(s) of Monetary Support

Please refer to primary and secondary sponsors