Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02043548
• Date of registration: 17/01/2014
• Prospective Registration: Yes
• Primary sponsor: Chester Oddis
• Public title: Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis TIM
• Scientific title: Tocilizumab in the Treatment of Refractory Polymyositis and Dermatomyositis
• Date of first enrolment: October 1, 2014
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02043548
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Chester V. Oddis, MD
• Affiliation: University of Pittsburgh

Key inclusion & exclusion criteria

Inclusion Criteria:

Patients will be included in the trial based on the following criteria:

1. Definite or probable polymyositis (PM )or dermatomyositis (DM) by the criteria of
Bohan and Peter (as modified by IMACS) in adults over the age of 18. We will also
allow enrollment of juvenile dermatomyositis(JDM) patients (considered to have DM)
over the age of 18 who otherwise meet the inclusion criteria stipulated below.

2. Subjects must either have the classic rash(es) of DM (heliotrope, Gottron sign or
Gottron papules), possess one of the myositis-associated autoantibodies (e.g.
anti-synthetase, anti-signal recognition particle (anti-SRP), anti-Mi-2, anti-PM-Scl,
transcription intermediary factor 1-? (anti TIF1-? etc.), or have the diagnosis of PM
agreed upon by a 3-member Adjudication Committee consisting of a rheumatologist,
neurologist and neuromuscular pathologist.

3. Refractory myositis patients are defined (see Section 3.1.1) as having failed (or
considered intolerant to) an adequate course of glucocorticoids or having failed
glucocorticoids and at least one other immunosuppressive (IS) or immunomodulatory
agent (e.g. methotrexate, azathioprine, cyclosporine, tacrolimus, mycophenolate
mofetil, cyclophosphamide, Intravenous immunoglobulin (IVIg), anti-tumor necrosis
factor (anti-TNF) agents, and rituximab).

4. Subjects with an Manual muscle score (MMT-8) score = 66 (see Appendix B) must also
have at least 2 other core set measures meeting the criteria listed below.

5. Subjects with an MMT-8 score > 66 must have at least 3 other core set measures meeting
the criteria listed below and a global extramuscular visual analog score (VAS) score
on the Myositis Disease Activity Assessment Tool ( MDAAT) = 5cm on a 10cm scale.

6. Criteria for core set measures for study entry:

1. Patient global VAS with a minimum value of 2.0cm on a 10cm scale.

2. MD global VAS with a minimum value of 2.0cm on a 10cm scale.

3. Health Assessment Questionnaire (HAQ) disability index with a minimum value of
0.25

4. Elevation of at least one of the muscle enzymes (Creatine kinase (CK), aspartate
aminotransferase (AST), alanine transaminase (ALT), aldolase, Lactate
dehydrogenase (LDH) at a minimum level of 1.3x the upper limit of normal (ULN).

5. Global extramuscular disease activity score with a minimum value of 1.0cm on a
10cm VAS scale on the Myositis Disease Activity Assessment Tool (MDAAT).

7. If on prednisone, the dose must be stable for 4 weeks prior to the screening visit.
Tapering of the prednisone dose will only be allowed after the subject meets the
Definition of Improvement (DOI) or if safety/toxicity issues supervene.

1. Prednisone Tapering: Prednisone should be held constant without tapering or
escalation (unless there is a serious adverse event or disease flare) until the
subject has achieved the DOI. Then, tapering of prednisone may commence using a
schedule approximating a 20-25% taper of the existing dose every 4 weeks based on
the clinical judgment of the clinical site investigator. Prednisone tapering
using the aforementioned guidelines can be commenced at any time if: (a) the
patient achieves the DOI or (b) there are complications or circumstances that, in
the clinical site investigator's opinion, necessitate the tapering of
corticosteroids.

2. Prednisone at Entry: It is also recommended that patients be on less than
1mg/kg/day of prednisone at study entry.

3. Prednisone Dosing During Flare: If in the clinical site investigator's opinion
there are complications or worsening of disease that necessitate an increase in
the prednisone dose then the smallest reasonable increase should be considered.

8. If an immunosuppressive (IS) agent was discontinued prior to the screening visit there
may be a washout as stipulated below or individualized according to the patients
treating physician:

1. 4 week washout for methotrexate

2. 8 week washout for any other IS agent (e.g. azathioprine, cyclosporine,
tacrolimus, mycophenolate mofetil)

3. 3 month washout for leflunomide, IVIg or cyclophosphamide

4. 6 month washout for rituximab

5. 8 week washout for infliximab or adalimumab

6. 2 week washout for etanercept

7. 1 week washout for anakinra

9. If an IS agent is continued, the dose must remain stable for 4 weeks prior to
enrollment and at least until the DOI is met or if safety/toxicity issues supervene.
Concomitant IS medications permitted include methotrexate, azathioprine, cyclosporine,
mycophenolate mofetil, and tacrolimus. IVIg will also be allowed as an
immunomodulatory agent. Careful patient safety monitoring along with American College
of Rheumatology (ACR) guidelines for monitoring these medications will be employed if
those toxicity monitoring laboratory studies are not already being assessed as part of
this trial. No concomitant biologic agents are allowed (rituximab, anti-TNFs,
abatacept) as well as cyclophosphamide or tofacitinib as concomitant immunosuppressive
agents. Investigators will be certain to assess and classify adverse events as being
secondary to either study drug as well as any concomitant immunosuppressive agent(s).
That is, there should be attribution of the adverse event (AE) to the appropriate
agent.

10. Normal organ function, except if abnormal due to the disease under investigation

11. Men and women of reproductive potential must agree to use an acceptable method of
birth control during treatment and for twelve months after completion of treatment.

12. Subject has provided written informed consent.

Exclusion Criteria:

A patient will be excluded if any of the following criteria are met:

1. Subjects under the age of 18.

2. Severe muscle damage defined as a global muscle damage score >5 on a 10cm VAS scale on
the Muscle Damage Index (MDI).

3. Evidence of active malignant disease, malignancies diagnosed within the previous 5
years (including hematological malignancies and solid tumors, except basal and
squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
been excised and cured), or breast cancer diagnosed within the previous 10 years
unless related to primary disease under investigation.

4. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other infections (including but


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Polymyositis

Dermatomyositis

Intervention(s)

Drug: tocilizumab

Drug: placebo

Primary Outcome(s)

Compare the Average Total Improvement Scores at Visits 2 Through 7 During the 6-month Treatment Period Between the Treatment and Placebo Arms [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Secondary Outcome(s)

Count of the Adverse Events Between the Treatment and Placebo Arms. [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Comparison of Individual Average Core Set Measure in Subjects Over Time Between the 2 Arms (Repeated Measures Analysis) [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Comparison of the Time to First Definition of Improvement (DOI) Between the 2 Arms [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Comparison of the Steroid-sparing Effect (Calculated Using Prednisone Dose Equivalents) Between the Treatment and Placebo Arms [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Magnitude of the Effect Size Between the Both Treatment Arms [Time Frame: Week 4, 8, 12, 16, 20, and 24]

Secondary ID(s)

ML28681

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.

Results

• Results available: Yes
• Date Posted: 30/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02043548