Abatacept in Juvenile Dermatomyositis

NCT02594735 | Completed Phase 4 Results

• 1 other identifier: IRB 111418
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and efficacy of subcutaneous abatacept in 10 patients seven years of age and older with refractory JDM.

Conditions

Dermatomyositis

Keywords

Juvenile dermatomyositis; inflammatory myopathies; Orencia; Abatacept

Outcome Measures

Primary Outcomes (2)

• 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).

  Improvement in myositis disease activity will be assessed using the IMACS myositis definition of improvement (DOI): at least 3 of 6 Core Set Measures (CSM) improved by ≥ 20% with no more than 2 CSM worsening by ≥ 25% (a worsening measure cannot be the manual muscle testing (MMT).

  week 0 to week 24

• Number of Treatment-emergent Adverse Events

  Safety will be assessed by review of adverse events using NCI Common Terminology criteria v5.0 November 2017. Particular attention to serious adverse events and infections will be given. An adverse event diary will be maintained throughout the study. Patient evaluations will include: vital sign measurement, physical examination, and laboratory parameters for hematology and routine chemistries

  week 0 to week 24

Secondary Outcomes (10)

• Total Improvement Score by IMACS Core Set Measures at Week 24

  week 0 to week 24

• Change in Corticosteroid Dose for Steroid-sparing Benefit From Baseline to Week 24

  week 0 to week 24

• Improvement in Physician Global Activity From Baseline to Week 24

  week 0 to week 24

• Improvement in Parent/Patient Global Activity From Baseline to Week 24

  week 0 to 24

• Improvement in Manual Muscle Testing (MMT8) From Baseline to Week 24

  week 0 to week 24

Study Arms (1)

Open Label (One Arm)

OTHER

A patient's participation in this study will last approximately 24 weeks ( screening visit and 5 intervention visits) with possible extension to 48 weeks. At screening, participants will have a physical exam, muscle strength assessment, blood and urine collection, and chest x-ray; they will also be asked to complete several questionnaires. All participants will receive each week subcutaneous injection of Abatacept. During intervention phase of the trial, muscle strength testing, physical exam, disease activity measurements, blood and urine collection, and muscle MRI will be performed. Participants will also be asked to complete several questionnaires. Participants will be also monitored closely for for serious drug related side effects.

Drug: Abatacept

Interventions

Abatacept DRUG

Study participation will consist of a screening visit and 5 protocol visits over six months (week 0, week 6, week 12, week 18, and week 24) for each subject, and phone follow-up (week 2, week 4, week 8, week 10, week 14, week 16, week 20, and week 22). At Visit 1, which will be treatment initiation, eligible subjects will be instructed on the use and side effects of subcutaneous abatacept and will be started on the study drug (abatacept 125 mg SQ weekly for subjects with body weight ≥ 50 KG or abatacept 87.5mg SQ for subjects with body weight \< 50 KG).

Also known as: Orencia

Open Label (One Arm)

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with definite or probable JDM and pediatric patients 7 years of age and older with definite or probable JDM.
• Body weight of at least 25 kg (or at least 55 lbs) and age ≥ 7 years of age.
• Patients must reside within the United States or Canada.
• 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.
• 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:
• 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.
• 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.
• If an immunosuppressive agent was discontinued prior to the screening visit then there must be a:
• week washout for prednisone or methotrexate
• week washout for any other IS agent
• For discontinuation of biologic therapies, a washout of 5 terminal half lives
• If on hydroxychloroquine or colchicine, the dose should be stable for 6 weeks prior to Visit 1.
• If on statin or fibric acid derivative agents, the dose should be stable for 6 weeks prior to Visit 1.

You may not qualify if:

• 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).
• 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)
• History of receiving a live vaccine 4 weeks prior to initiation of study treatment
• Joint disease, severe calcinosis, or other musculoskeletal condition, which precludes the ability to quantitate muscle strength.
• Wheelchair bound patients.
• Known hypersensitivity to abatacept or prior receipt of abatacept
• Concomitant illness that would prevent adequate patient assessment or in the investigators opinion pose an added risk for study participants:
• 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)
• 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
• Have a history of disseminated/complicated herpes zoster (for example, multi-dermatomal involvement, ophthalmic zoster, central nervous system (CNS) involvement, post-herpetic neuralgia)
• Known liver disease (i.e. cirrhosis or other conditions compromising the synthetic function of the liver)
• Disorders that would preclude accurate assessment of neuromuscular function
• Cardiomyopathy or arrhythmias that in the investigators opinion poses an additional risk for study participants
• New York Heart Association Classification III or IV for congestive heart failure
• Psychiatric illness that precludes compliance or neuromuscular assessment

Sponsors & Collaborators

• George Washington University: lead

Study Sites (1)

2300 M Street, 9th floor. Medical Faculty Associates, The George Washington University.

Washington D.C., District of Columbia, 20037, United States

Location

Related Publications (16)

• Feldman BM, Rider LG, Reed AM, Pachman LM. Juvenile dermatomyositis and other idiopathic inflammatory myopathies of childhood. Lancet. 2008 Jun 28;371(9631):2201-12. doi: 10.1016/S0140-6736(08)60955-1.

  PMID: 18586175 BACKGROUND

• Wedderburn LR, Rider LG. Juvenile dermatomyositis: new developments in pathogenesis, assessment and treatment. Best Pract Res Clin Rheumatol. 2009 Oct;23(5):665-78. doi: 10.1016/j.berh.2009.07.007.

  PMID: 19853831 BACKGROUND

• Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE; RIM Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.

  PMID: 23124935 BACKGROUND

• Nagaraju K, Raben N, Villalba ML, Danning C, Loeffler LA, Lee E, Tresser N, Abati A, Fetsch P, Plotz PH. Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells. Clin Immunol. 1999 Aug;92(2):161-9. doi: 10.1006/clim.1999.4743.

  PMID: 10444360 BACKGROUND

• Murata K, Dalakas MC. Expression of the costimulatory molecule BB-1, the ligands CTLA-4 and CD28, and their mRNA in inflammatory myopathies. Am J Pathol. 1999 Aug;155(2):453-60. doi: 10.1016/s0002-9440(10)65141-3.

  PMID: 10433938 BACKGROUND

• Behrens L, Kerschensteiner M, Misgeld T, Goebels N, Wekerle H, Hohlfeld R. Human muscle cells express a functional costimulatory molecule distinct from B7.1 (CD80) and B7.2 (CD86) in vitro and in inflammatory lesions. J Immunol. 1998 Dec 1;161(11):5943-51.

  PMID: 9834075 BACKGROUND

• Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993 Nov 4;366(6450):76-9. doi: 10.1038/366076a0.

  PMID: 7694153 BACKGROUND

• Schiff M. Subcutaneous abatacept for the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2013 Jun;52(6):986-97. doi: 10.1093/rheumatology/ket018. Epub 2013 Mar 5.

  PMID: 23463804 BACKGROUND

• Arabshahi B, Silverman RA, Jones OY, Rider LG. Abatacept and sodium thiosulfate for treatment of recalcitrant juvenile dermatomyositis complicated by ulceration and calcinosis. J Pediatr. 2012 Mar;160(3):520-2. doi: 10.1016/j.jpeds.2011.11.057. Epub 2012 Jan 13.

  PMID: 22244459 BACKGROUND

• Musuruana JL, Cavallasca JA. Abatacept for treatment of refractory polymyositis. Joint Bone Spine. 2011 Jul;78(4):431-2. doi: 10.1016/j.jbspin.2011.03.022. Epub 2011 May 7. No abstract available.

  PMID: 21550833 BACKGROUND

• Maeshima K, Kiyonaga Y, Imada C, Iwakura M, Hamasaki H, Haranaka M, Ishii K. Successful treatment of refractory anti-signal recognition particle myopathy using abatacept. Rheumatology (Oxford). 2014 Feb;53(2):379-80. doi: 10.1093/rheumatology/ket251. Epub 2013 Aug 6. No abstract available.

  PMID: 23920268 BACKGROUND

• Ruperto N, Lovell DJ, Li T, Sztajnbok F, Goldenstein-Schainberg C, Scheinberg M, Penades IC, Fischbach M, Alcala JO, Hashkes PJ, Hom C, Jung L, Lepore L, Oliveira S, Wallace C, Alessio M, Quartier P, Cortis E, Eberhard A, Simonini G, Lemelle I, Chalom EC, Sigal LH, Block A, Covucci A, Nys M, Martini A, Giannini EH; Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1542-51. doi: 10.1002/acr.20283. Epub 2010 Jul 1.

  PMID: 20597110 BACKGROUND

• Rider LG, Giannini EH, Brunner HI, Ruperto N, James-Newton L, Reed AM, Lachenbruch PA, Miller FW; International Myositis Assessment and Clinical Studies Group. International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum. 2004 Jul;50(7):2281-90. doi: 10.1002/art.20349.

  PMID: 15248228 BACKGROUND

• Ruperto N, Pistorio A, Ravelli A, Rider LG, Pilkington C, Oliveira S, Wulffraat N, Espada G, Garay S, Cuttica R, Hofer M, Quartier P, Melo-Gomes J, Reed AM, Wierzbowska M, Feldman BM, Harjacek M, Huppertz HI, Nielsen S, Flato B, Lahdenne P, Michels H, Murray KJ, Punaro L, Rennebohm R, Russo R, Balogh Z, Rooney M, Pachman LM, Wallace C, Hashkes P, Lovell DJ, Giannini EH, Gare BA, Martini A; Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis. Arthritis Care Res (Hoboken). 2010 Nov;62(11):1533-41. doi: 10.1002/acr.20280. Epub 2010 Jun 25.

  PMID: 20583105 BACKGROUND

• Lazarevic D, Pistorio A, Palmisani E, Miettunen P, Ravelli A, Pilkington C, Wulffraat NM, Malattia C, Garay SM, Hofer M, Quartier P, Dolezalova P, Penades IC, Ferriani VP, Ganser G, Kasapcopur O, Melo-Gomes JA, Reed AM, Wierzbowska M, Rider LG, Martini A, Ruperto N; Paediatric Rheumatology International Trials Organisation (PRINTO). The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis. Ann Rheum Dis. 2013 May;72(5):686-93. doi: 10.1136/annrheumdis-2012-201483. Epub 2012 Jun 26.

  PMID: 22736096 BACKGROUND

• Curiel RV, Nguyen W, Mamyrova G, Jones D, Ehrlich A, Brindle KA, Haji-Momenian S, Sheets R, Kim H, Jones OY, Rider LG; Abatacept in Dermatomyositis (AID) Trial Investigators. Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy. Arthritis Rheumatol. 2023 Jul;75(7):1229-1237. doi: 10.1002/art.42450. Epub 2023 Jun 7.

  PMID: 36657109 DERIVED

MeSH Terms

Conditions

Dermatomyositis; Myositis

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Polymyositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Limitations and Caveats

Non-randomized open label study design

Results Point of Contact

• Title: Dr. Rodolfo Curiel
• Organization: GWU Myositis Center

rcuriel@gwu.edu

202-741-2488

Study Officials

• Rodolfo V Curiel, MD

  The George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Rodolfo V. Curiel, MD, Associate Professor of Medicine, Division of Rheumatology; Director, Myositis Center

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: November 3, 2015
• Study Start: November 1, 2015
• Primary Completion: July 16, 2021
• Study Completion: October 22, 2021
• Last Updated: August 29, 2022
• Results First Posted: August 29, 2022

Record last verified: 2022-08

Locations

US (1)