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A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica

Primary Purpose

Polymyalgia Rheumatica, Inflammatory Diseases

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AIN457
ACZ885
Prednisone
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polymyalgia Rheumatica focused on measuring Polymyalgia Rheumatica, Inflammatory Disease, Rheumatic Disease

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must meet all of the following features:
  • Patients ≥ 50 and ≤ 85 years
  • C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr
  • New bilateral shoulder and/or hip pain
  • Early morning stiffness ≥ 60 min
  • Duration of illness > 1 week
  • A negative 5 U purified protein derivative skin test (PPD) skin test (≤ 5 mm induration) at screening

Exclusion Criteria:

  • Active infection or current use of antibiotics
  • Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV)
  • Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline
  • History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry
  • Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis.

Other protocol-defined inclusion/exclusion criteria apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Other

Arm Label

ACZ885

AIN457

Prednisone

Arm Description

On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.

On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.

On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.

Outcomes

Primary Outcome Measures

Polymyalgia Rheumatica Activity Score (PMR-AS)
The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.

Secondary Outcome Measures

Time to Partial Clinical Response
The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had: >50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.
Time to Complete Clinical Response
The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.
Time to First Flare
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44
Number of Flares Over a 6 Month Period
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Mean Steroid Dose Over a 6 Month Period
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.
One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.
Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
The Short Form-36 (SF-36) Questionnaire is a 36-item questionnaire yields an 8-scale health profile as well as summary measures of individual patients.. The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Pharmacokinetics of AIN457 and ACZ885 - Cmax
Pharmacokinetics of AIN457 and ACZ885 - Tmax
Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
Pharmacokinetics of AIN457 and ACZ885 - CL
Pharmacokinetics of AIN457 and ACZ885 - Vz
Pharmacokinetics of AIN457 and ACZ885 - T1/2

Full Information

First Posted
March 10, 2011
Last Updated
August 17, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01364389
Brief Title
A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica
Official Title
A 2-week Single-blind, Randomized, 3-arm Proof of Concept Study of the Effects of AIN457 (Anti-IL17 Antibody), ACZ885 (Canakinumab, Anti-IL1b Antibody), or Corticosteroids in Patients With Polymyalgia Rheumatica, Followed by an Open Label Phase to Assess Safety and Long Term Efficacy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.
Study Start Date
February 14, 2011 (Actual)
Primary Completion Date
January 29, 2013 (Actual)
Study Completion Date
January 29, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. The protocol will seek to enroll a total of 30 patients, who will be randomized to the 3 arms at a ratio of 1:1:1. Patients will have a maximum screening period of 7 days with randomization at D1 for a dosing period of 15 days followed by a follow up-period of 154 days, or 4 months (112 days) after their last biologic dose, whichever is greater, and followed by unblinded re-dosing in the case of a disease flare.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polymyalgia Rheumatica, Inflammatory Diseases
Keywords
Polymyalgia Rheumatica, Inflammatory Disease, Rheumatic Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACZ885
Arm Type
Experimental
Arm Description
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Arm Title
AIN457
Arm Type
Experimental
Arm Description
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
Arm Title
Prednisone
Arm Type
Other
Arm Description
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Intervention Type
Drug
Intervention Name(s)
AIN457
Intervention Description
3 mg/kg
Intervention Type
Drug
Intervention Name(s)
ACZ885
Other Intervention Name(s)
canakinumab
Intervention Description
3 mg/kg
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
20 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to AIN457, ACZ885 and prednisone
Primary Outcome Measure Information:
Title
Polymyalgia Rheumatica Activity Score (PMR-AS)
Description
The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
Time Frame
Baseline, Day 15
Secondary Outcome Measure Information:
Title
Time to Partial Clinical Response
Description
The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had: >50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.
Time Frame
Day 15
Title
Time to Complete Clinical Response
Description
The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.
Time Frame
Day 15
Title
Time to First Flare
Description
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44
Time Frame
6 months
Title
Number of Flares Over a 6 Month Period
Description
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Time Frame
6 months
Title
Mean Steroid Dose Over a 6 Month Period
Description
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Time Frame
6 months
Title
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Time Frame
6 months
Title
Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.
Description
One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.
Time Frame
6 months
Title
Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
Description
The Short Form-36 (SF-36) Questionnaire is a 36-item questionnaire yields an 8-scale health profile as well as summary measures of individual patients.. The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame
6 months
Title
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
Description
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Time Frame
baseline and at month 6
Title
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6
Description
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Time Frame
6 months
Title
Pharmacokinetics of AIN457 and ACZ885 - Cmax
Time Frame
Day 15
Title
Pharmacokinetics of AIN457 and ACZ885 - Tmax
Time Frame
Day 15
Title
Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
Time Frame
Day 15
Title
Pharmacokinetics of AIN457 and ACZ885 - CL
Time Frame
Day 15
Title
Pharmacokinetics of AIN457 and ACZ885 - Vz
Time Frame
Day 15
Title
Pharmacokinetics of AIN457 and ACZ885 - T1/2
Time Frame
Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must meet all of the following features: Patients ≥ 50 and ≤ 85 years C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr New bilateral shoulder and/or hip pain Early morning stiffness ≥ 60 min Duration of illness > 1 week A negative 5 U purified protein derivative skin test (PPD) skin test (≤ 5 mm induration) at screening Exclusion Criteria: Active infection or current use of antibiotics Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV) Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis. Other protocol-defined inclusion/exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Novartis Investigative Site
City
Reggio Emilia
State/Province
RE
ZIP/Postal Code
42123
Country
Italy
Facility Name
Novartis Investigative Site
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
Novartis Investigative Site
City
Basildon
State/Province
Essex
ZIP/Postal Code
SS16 5NL
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Westcliff-on-Sea
State/Province
Essex
ZIP/Postal Code
SS0 0RY
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica

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