Single Patient Study to Treat Relapsing Polychondritis With Tocilizumab

• Sponsor: Children's Hospital of Eastern Ontario (Other)
• Overall Status: Completed
• CT.gov ID: NCT01041248
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 0

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
Relapsing Polychondritis	Drug: Tocilizumab	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

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of Tocilizumab in a Patient With Relapsing Polychondritis
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

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: Actemra

Outcome Measures

Primary Outcome Measures

1. 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

1. Prednisone Dose [30 weeks]

   Prednisone dose administered to patient reduction through treatment course

2. 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

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

• Kawai M, Hagihara K, Hirano T, Shima Y, Kuwahara Y, Arimitsu J, Narazaki M, Ogata A, Kawase I, Kishimoto T, Tanaka T. Sustained response to tocilizumab, anti-interleukin-6 receptor antibody, in two patients with refractory relapsing polychondritis. Rheumatology (Oxford). 2009 Mar;48(3):318-9. doi: 10.1093/rheumatology/ken468. Epub 2008 Dec 23.

• Responsible Party: Johannes Roth, Pediatric Rheumatologist, Children's Hospital of Eastern Ontario
• ClinicalTrials.gov Identifier: NCT01041248
• Other Study ID Numbers: ML 25245
• First Posted: Dec 31, 2009
• Last Update Posted: Mar 3, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by Johannes Roth, Pediatric Rheumatologist, Children's Hospital of Eastern Ontario: Relapsing Polychondritis; Single Patient Study; Tocilizumab
• Additional relevant MeSH terms: Polychondritis, Relapsing

Study Results

Participant Flow

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

1. Primary Outcome

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

2. Secondary Outcome

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

3. Secondary Outcome

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
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

[Not Specified]

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.