A Phase 2 interventional study of tocilizumab and placebo in Dermatomyositis and Polymyositis, sponsored by Chester Oddis. Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-30.
Sponsored by Chester Oddis · Phase 2, Interventional, and Treatment
The purpose of this multi-center pilot study is to determine if the drug tocilizumab (Actemra) is effective in the treatment of patients with refractory adult polymyositis (PM) and dermatomyositis (DM).
Although there are several studies supporting the efficacy of tocilizumab (TCZ) in Rheumatoid Arthritis (RA) and systemic onset juvenile idiopathic arthritis, it's use in other autoimmune disorders has also been propose. A consensus statement on blocking the effects of IL-6 in RA and other autoimmune conditions has been recently published. IL-6 is involved in the growth and differentiation of many inflammatory cells. In addition to its initial role in triggering B-cell stimulating factor, it also induces T cell growth and differentiation and plays a critical role in both adaptive and innate immune responses. IL-6, produced by many cells including T cells, B cells, monocytes and endothelial cells, binds to its receptor (IL-6R) and subsequently triggers several intracellular pathways leading to the release of inflammatory mediators and stimulation of the immune system. Inhibition of IL-6 has been studied in phase II and III clinical trials of RA. It has led to a decrease in acute phase reactants and other indicators of chronic inflammation. IL-6 is also a potential therapeutic target in systemic sclerosis, and since IL-6 induces differentiation of B cells into antibody forming cells and contributes to T cells transforming into effector cells, its use in Systemic Lupus erythematosus (SLE) has also been suggested.
The use of TCZ in myositis proposed in this protocol is supported by the aforementioned rationale and its efficacy in other rheumatologic disorders. Patients with refractory polymyositis (PM) were treated with tocilizumab and responded favorably. In dermatomyositis, tissue inflammation implicates soluble cytokine networks contributing to disease pathogenesis. Work on a mouse model of myositis noted IL-6 as a mediator of muscle inflammation. Other investigators studying peripheral blood samples and clinical data on both adult and juvenile dermatomyositis (DM) noted that serum levels of IL-6 were significantly correlated with disease activity. In this same study, correlations between serum IL-6 levels and both the type I interferon gene and chemokine signatures were also identified in DM. These authors suggest that the coordinated dysregulation of IL-6 production and Type I interferon signaling implicates these pathways as contributing to disease pathogenesis in DM.
In a mouse model of PM, C protein-induced myositis (CIM), the pathology reportedly mimics that seen in human PM. Mice were treated with anti-IL-6 receptor monoclonal antibodies or control antibodies and muscle tissue was histologically and immunohistochemically analyzed. CIM was ameliorated in this mouse model implicating IL-6 in the development of myositis. These results not only identified this model as useful to understanding PM but they suggest that IL-6 blockade be considered as a new therapeutic approach in the treatment of myositis.
Thus, the collective findings described above provide evidence for the involvement of IL-6 in the pathogenesis of both adult PM and DM as well as supporting its role from animal models and human studies.
184 studies on the registry are indexed under Dermatomyositis; 63 are open to participants now.
This study's enrollment of 36 is close to the median of 35 across 130 interventional studies indexed under Dermatomyositis.
Browse Dermatomyositis studies →This is the only study on the registry with Chester Oddis as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients will be included in the trial based on the following criteria:
Criteria for core set measures for study entry:
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.
If an immunosuppressive (IS) agent was discontinued prior to the screening visit there may be a as stipulated below or individualized according to the patients treating physician:
Exclusion Criteria:
A patient will be excluded if any of the following criteria are met:
Abnormal laboratory values noted below:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Tocilizumab will be given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
Drug: tocilizumab
Placebo arm - no active drug
Drug: placebo
given at a dose of 8mg/kg by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
Also known as: Actemra
given by IV infusion every 4 weeks at 6 time points (Visits 1, 2, 3, 4, 5 and 6).
Compare the Average Total Improvement Scores at Visits 2 Through 7 During the 6-month Treatment Period Between the Treatment and Placebo Arms
The total improvement score was calculated by adding the improvement scores of all six core set measures based on 2016 American College of Rheumatology (ACR)/European League Against Rheumatism(EULAR) myositis response criteria. The minimum and maximum values of the average Total Improvement Scores are 0 and 100; The minimum and maximum values of the average Total Improvement Scores of our included patients are 5.0 and 67.1; The higher scores mean a better outcome.
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 to achieve the first DOI between the treatment and placebo arms.The total improvement score (TIS) is the sum of all 6 improvement scores associated with the change in each core set measure. A TIS \>= 20 represents minimal improvement, a score of \>=40 represents moderate improvement, and a score of \>=60 represents major improvement.
Time frame: Week 4, 8, 12, 16, 20, and 24
Count of the Adverse Events Between the Treatment and Placebo Arms.
We compared the count of the adverse events between the treatment and placebo arms statistically.
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
Mean change of steroid dose prednisone equivalent from last visit to baseline visit was compared between the two treatment 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)
The core set measure tested was manual muscle testing, and we compared the mean manual muscle test measures in subjects over time. The minimum and maximum values of the manual muscle testing are 0 and 150; The minimum and maximum values of the manual muscle testing of our included patients are 97.0 and 150.0; The higher scores mean a better outcome.
Time frame: Week 4, 8, 12, 16, 20, and 24
Magnitude of the Effect Size Between the Both Treatment Arms
Compared the number of subjects meeting total improvement scores \>=20 (minimal) and \>=40 (moderate) and \>=60 (major) based on 2016 ACR EULAR myositis response criteria for treatment group and placebo group. The highest TIS score achieved from week 4 through week 24 was used to determine the effect size between both treatment arms.
Time frame: Week 4, 8, 12, 16, 20, and 24
Adult refractory dermatomyositis and polymyositis
| Milestone | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Started | 18 | 18 |
| Completed | 17 | 17 |
| Not completed | 1 | 1 |
| Withdrew: Lack of efficacy | 1 | 0 |
| Withdrew: Adverse event | 0 | 1 |
The total improvement score was calculated by adding the improvement scores of all six core set measures based on 2016 American College of Rheumatology (ACR)/European League Against Rheumatism(EULAR) myositis response criteria. The minimum and maximum values of the average Total Improvement Scores are 0 and 100; The minimum and maximum values of the average Total Improvement Scores of our included patients are 5.0 and 67.1; The higher scores mean a better outcome.
| score on a scale | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Compare the Average Total Improvement Scores at Visits 2 Through 7 During the 6-month Treatment Period Between the Treatment and Placebo Arms | 26.4 ± 16.8 | 29.3 ± 16.8 |
Time to achieve the first DOI between the treatment and placebo arms.The total improvement score (TIS) is the sum of all 6 improvement scores associated with the change in each core set measure. A TIS \>= 20 represents minimal improvement, a score of \>=40 represents moderate improvement, and a score of \>=60 represents major improvement.
| days | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Comparison of the Time to First Definition of Improvement (DOI) Between the 2 Arms | 42.4 (27.5 to 90.4) | 55.5 (29.4 to 114.6) |
We compared the count of the adverse events between the treatment and placebo arms statistically.
| events | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Count of the Adverse Events Between the Treatment and Placebo Arms. | 14 | 9 |
Mean change of steroid dose prednisone equivalent from last visit to baseline visit was compared between the two treatment arms
| mg | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Comparison of the Steroid-sparing Effect (Calculated Using Prednisone Dose Equivalents) Between the Treatment and Placebo Arms | 0.0 (0 to 0) | 0.0 (0 to 5) |
The core set measure tested was manual muscle testing, and we compared the mean manual muscle test measures in subjects over time. The minimum and maximum values of the manual muscle testing are 0 and 150; The minimum and maximum values of the manual muscle testing of our included patients are 97.0 and 150.0; The higher scores mean a better outcome.
| score on a scale | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Comparison of Individual Average Core Set Measure in Subjects Over Time Between the 2 Arms (Repeated Measures Analysis) | 130.7 ± 16.94 | 137.3 ± 11.83 |
Compared the number of subjects meeting total improvement scores \>=20 (minimal) and \>=40 (moderate) and \>=60 (major) based on 2016 ACR EULAR myositis response criteria for treatment group and placebo group. The highest TIS score achieved from week 4 through week 24 was used to determine the effect size between both treatment arms.
| participants | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Minimal Improvement | 3 | 7 |
| Moderate Improvement | 4 | 6 |
| Major Improvement | 3 | 2 |
Collected over Time frame period beginning with any amount of exposure to Tocilizumab through the protocol-defined follow-up period. Total duration 1 year.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group A: Tocilizumab | 0/18 (0%) | 1/18 (5.6%) | 11/18 (61.1%) |
| Group B: Placebo | 0/18 (0%) | 0/18 (0%) | 8/18 (44.4%) |
| Event | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| Bilateral sub-massive pulmonary embolismCardiac disorders | 1/18 | 0/18 |
| Event | Group A: Tocilizumab | Group B: Placebo |
|---|---|---|
| SinusitisInfections and infestations | 4/18 | 3/18 |
| Upper Respiratory InfectionInfections and infestations | 3/18 | 1/18 |
| Herpes ZosterInfections and infestations | 0/18 | 2/18 |
| General disorders and administration site conditionsInjury, poisoning and procedural complications | 1/18 | 0/18 |
| DepressionPsychiatric disorders | 1/18 | 0/18 |
| pruritisSkin and subcutaneous tissue disorders | 1/18 | 0/18 |
| HypertensionVascular disorders | 1/18 | 0/18 |
| Muscle CrampsMusculoskeletal and connective tissue disorders | 0/18 | 1/18 |
| HeadacheNervous system disorders | 0/18 | 1/18 |
| Age, Categorical(Participants) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 15 | 16 | 31 |
| >=65 years | 3 | 2 | 5 |
| Age, Continuous(years) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| Mean | 52.3 (31.3 to 83.4) | 50.4 (21.5 to 70.7) | 52.3 (21.5 to 83.4) |
| Sex: Female, Male(Participants) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| Female | 15 | 13 | 28 |
| Male | 3 | 5 | 8 |
| Ethnicity (NIH/OMB)(Participants) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 2 | 3 |
| Not Hispanic or Latino | 17 | 16 | 33 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 1 | 2 |
| Black or African American | 3 | 3 | 6 |
| White | 12 | 14 | 26 |
| Unknown or Not Reported | 2 | 0 | 2 |
| Dermatomyositis vs. polymyositis per treatment group(Participants) | Group A: Tocilizumab | Group B: Placebo | Total |
|---|---|---|---|
| Dermatomyositis | 10 | 13 | 23 |
| Polymyositis | 8 | 5 | 13 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Oct 2014 to primary completion in Jul 2019, 57 months.
Results were first posted in Oct 2020, 1 year 3 months after primary completion. A results delay was requested in Jul 2020.
Of 19 phase 2 interventional studies under Dermatomyositis, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 52. This study's 57 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tocilizumab