Single Patient Study to Treat Relapsing Polychondritis With Tocilizumab
Study Details
Study Description
Brief Summary
Relapsing polychondritis (RP) is a rare, immune-mediated disease associated with inflammation in cartilaginous structures and other tissues throughout the body. Prognosis can be poor, especially in cases where there is acute involvement of the laryngotracheal cartilages leading to airway destruction, which are resistant to treatments such as corticosteroids, immunosuppressive or cytotoxic drugs. The pathogenesis remains unclear although it is thought that autoimmune reactions to antigens present in cartilages, such as type II collagen and matrilin may evoke symptoms. There are no known clinical or laboratory measures that predict the expression of specific disease manifestations or the overall disease course. Two recently published case reports have shown an association with elevated serum IL-6 levels and relapsing polychondritis. In these case reports, both patients with refractory relapsing polychondritis were treated with tocilizumab, a humanized monoclonal antibody to the Interleukin 6 receptor, and achieved sustained response to the drug. This single patient trial aims to evaluate the response to Tocilizumab in an eight year old boy with relapsing polychondritis who has been shown to have elevated serum IL-6 levels and who has responded poorly to conventional therapies. The study hypothesis is that Tocilizumab will be able to control the disease in this patient.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
N/A |
Detailed Description
In this N = 1 study a single known patient with relapsing polychondritis who has failed methotrexate, various anti TNF medications, anti IL1 medication and prolongued glucocorticosteroids will be recruited to receive Tocilizumab 8 mg /kg q 2 weeks iv.
The objective is to assess efficacy of tociliuzmab in combination with stable ongoing therapy. Our patient received tocilizumab 8 mg/kg over 1 hour by intravenous infusion every 2 weeks throughout the course of the study. To assess tocilizumab efficacy, the primary objective is the change in physician global assessment on a 100-mm horizontal visual analogue scale (VAS) of disease activity.
The secondary objectives were the change in parent global assessment of disease activity on a 100 mm VAS and the glucocorticoid dose in mg per day. Frequency of adverse events was also measured at baseline and after each biweekly tocilizumab infusion.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Tocilizumab Single arm open label study. In this arm patient will receive 8mg/kg of Tocilizumab q 2 weeks iv. |
Drug: Tocilizumab
8mg/kg every 2 weeks i.v.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Physician Global Assessment of Disease Activity [Baseline and then every 2 weeks prior to each infusion for total duration of 30 weeks]
Physician global assessment of disease activity was assessed on a 100 mm Visual Analogue Scale where 0 would be no disease activity and 100 would be the maximum disease activity. Higher values therefore indicate higher disease activity and therefore a worse outcome. Change of this outcome measure over time was documented.
Secondary Outcome Measures
- Prednisone Dose [30 weeks]
Prednisone dose administered to patient reduction through treatment course
- Parent/Patient Global Assessment of Overall Well Being [30 weeks]
A 100 mm visual analogue scale was used for the assessment of the parent/patient globale well being, maximum value is 100 and minimum value is 0 with lower values being better well being and therefore improved outcome and higher values worse well being and therefore worse outcome. Changes in this score over time are being assessed with this measure.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Refractory relapsing polychondritis
-
Failed glucocorticoid and methotrexate therapy
Exclusion Criteria:
- This is an N=1 clinical trial with a known patient, therefore, exclusion criteria are non-applicable.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
Sponsors and Collaborators
- Children's Hospital of Eastern Ontario
Investigators
- Principal Investigator: Johannes Roth, MD, Children's Hospital of Eastern Ontario
Study Documents (Full-Text)
None provided.More Information
Publications
- ML 25245
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Tocilizumab |
---|---|
Arm/Group Description | Tocilizumab: 8mg/kg every 2 weeks i.v. |
Period Title: Overall Study | |
STARTED | 1 |
COMPLETED | 1 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Tocilizumab |
---|---|
Arm/Group Description | Tocilizumab: 8mg/kg every 2 weeks i.v. |
Overall Participants | 1 |
Age (Count of Participants) | |
<=18 years |
1
100%
|
Between 18 and 65 years |
0
0%
|
>=65 years |
0
0%
|
Age (years) [Mean (Full Range) ] | |
Mean (Full Range) [years] |
10
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
1
100%
|
Race and Ethnicity Not Collected (Count of Participants) | |
Region of Enrollment (participants) [Number] | |
Canada |
1
100%
|
Outcome Measures
Title | Physician Global Assessment of Disease Activity |
---|---|
Description | Physician global assessment of disease activity was assessed on a 100 mm Visual Analogue Scale where 0 would be no disease activity and 100 would be the maximum disease activity. Higher values therefore indicate higher disease activity and therefore a worse outcome. Change of this outcome measure over time was documented. |
Time Frame | Baseline and then every 2 weeks prior to each infusion for total duration of 30 weeks |
Outcome Measure Data
Analysis Population Description |
---|
a known patient for whom this trial was designed was recruited into this open label single arm study |
Arm/Group Title | Tocilizumab |
---|---|
Arm/Group Description | Tocilizumab: 8mg/kg every 2 weeks i.v. |
Measure Participants | 1 |
Baseline |
21
|
2 weeks |
14
|
4 weeks |
12
|
6 weeks |
43
|
8 weeks |
14
|
10 weeks |
12
|
12 weeks |
8
|
14 weeks |
6
|
16 weeks |
5
|
18 weeks |
8
|
20 weeks |
0
|
22 weeks |
2
|
24 weeks |
0
|
26 weeks |
37
|
28 weeks |
19
|
30 weeks |
0
|
Title | Prednisone Dose |
---|---|
Description | Prednisone dose administered to patient reduction through treatment course |
Time Frame | 30 weeks |
Outcome Measure Data
Analysis Population Description |
---|
single arm open label study for 1 patient with relapsing polychondritis |
Arm/Group Title | Tocilizumab |
---|---|
Arm/Group Description | treatment arm |
Measure Participants | 1 |
Baseline |
25
|
2 weeks |
25
|
4 weeks |
25
|
6 weeks |
25
|
8 weeks |
25
|
10 weeks |
30
|
12 weeks |
30
|
14 weeks |
30
|
16 weeks |
30
|
18 weeks |
30
|
20 weeks |
25
|
22 weeks |
25
|
24 weeks |
25
|
26 weeks |
20
|
28 weeks |
20
|
30 weeks |
20
|
Title | Parent/Patient Global Assessment of Overall Well Being |
---|---|
Description | A 100 mm visual analogue scale was used for the assessment of the parent/patient globale well being, maximum value is 100 and minimum value is 0 with lower values being better well being and therefore improved outcome and higher values worse well being and therefore worse outcome. Changes in this score over time are being assessed with this measure. |
Time Frame | 30 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Patient receiving Tocilizumab |
Arm/Group Title | Tocilizumab |
---|---|
Arm/Group Description | treatment arm |
Measure Participants | 1 |
Baseline |
53
|
2 weeks |
0
|
4 weeks |
0
|
6 weeks |
33
|
8 weeks |
12
|
10 weeks |
2
|
12 weeks |
0
|
14 weeks |
1
|
16 weeks |
1
|
18 weeks |
2
|
20 weeks |
0
|
22 weeks |
1
|
24 weeks |
0
|
26 weeks |
30
|
28 weeks |
15
|
30 weeks |
0
|
Adverse Events
Time Frame | 30 weeks | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Tocilizumab | |
Arm/Group Description | Tocilizumab: 8mg/kg every 2 weeks i.v. | |
All Cause Mortality |
||
Tocilizumab | ||
Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) | |
Serious Adverse Events |
||
Tocilizumab | ||
Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Tocilizumab | ||
Affected / at Risk (%) | # Events | |
Total | 0/1 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr Johannes Roth |
---|---|
Organization | Childrens Hospital of Eastern Ontario |
Phone | 6137377600 ext 1015 |
jroth@cheo.on.ca |
- ML 25245