Polymyalgia Rheumatica
Conditions
Keywords
Polymyalgia Rheumatica, PMR, ABBV-154, Glucocorticoid
Brief summary
Polymyalgia rheumatica (PMR) is an inflammatory disease causing shoulder, hip, and neck pain and stiffness, in adults aged 50 years or older. This study evaluates how safe and effective ABBV-154 is in participants with glucocorticoid-dependent PMR. Adverse events and change in disease activity will be assessed. ABBV-154 is an investigational drug being evaluated for the treatment of PMR. Participants will be randomized into 1 of 4 treatment groups or arms, each arm receiving a different treatment. There is a 1 in 4 chance that a participant will be assigned to placebo. Around 160 participants, of at least 50 years of age, with PMR will be enrolled in the study at approximately 95 sites worldwide. The study is compromised of a 52 week double-blind, placebo-controlled period and a follow-up visit 70 days after the last dose of the study drug. All participants will receive a glucocorticoid taper along with the assigned dose of ABBV-154 or placebo, subcutaneously (SC) every other week (eow). There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of Polymyalgia Rheumatica (PMR) and fulfillment of the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) provisional classification criteria for PMR. * Must have had at least 2 episodes of unequivocal PMR flare. * Must be on a stable dose of prednisone. * Must be willing to follow the protocol-defined glucocorticoid tapering regimen.
Exclusion criteria
* Have been treated with a prior TNF antagonist. * Current use of immunomodulators other than prednisone and hydroxychloroquine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Flare | From first dose of study drug to Week 52 | Flare is defined as, presence of clinical signs and symptoms of PMR and requirement to increase the glucocorticoid dose per investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Flare-Free State | Up to Week 24 | Percentage of participants achieving flare-free state. |
| Cumulative Glucocorticoid Dose | Week 24 | Cumulative glucocorticoid dose. |
| Change From Baseline in Glucocorticoid Dose | Week 24 | Change from Baseline in glucocorticoid dose. |
Countries
Australia, Austria, Canada, France, Germany, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
In this Double-Blind study, 181 glucocorticoid dependent PMR subjects were randomized into 4 groups and dosed for 52 weeks. Subjects were dosed SC: Placebo, ABBV-154 (40mg,150mg, or 340mg) with a glucocorticoid taper EOW. Beginning at Week 3, subjects were to taper prednisone/prednisolone per the protocol-defined glucocorticoid taper schedule to 0mg prednisone equivalent by Week 24.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneously (SC) every other week (eow) for 52 weeks. In addition, participants received a glucocorticoid oral tablet taper.
Placebo: Subcutaneous Injection Glucocorticoid: Oral Tablet | 50 |
| ABBV-154 40mg SC Participants in this group received 40mg dose of ABBV-154 SC eow for 52 weeks. In addition, participants received a glucocorticoid oral tablet taper.
ABBV-154: Subcutaneous Injection Glucocorticoid: Oral Tablet | 42 |
| ABBV-154 150mg SC Participants in this group received 150mg dose of ABBV-154 SC eow for 52 weeks. In addition, participants received a glucocorticoid oral tablet taper.
ABBV-154: Subcutaneous Injection Glucocorticoid: Oral Tablet | 45 |
| ABBV-154 340mg SC Participants in this group received 340mg dose of ABBV-154 SC eow for 52 weeks. In addition, participants received a glucocorticoid oral tablet taper.
ABBV-154: Subcutaneous Injection Glucocorticoid: Oral Tablet | 44 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 | 1 | 7 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 1 | 1 |
| Overall Study | Study Terminated by Sponsor | 25 | 28 | 32 | 27 |
| Overall Study | Withdrawal by Subject | 7 | 4 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | ABBV-154 40mg SC | ABBV-154 150mg SC | ABBV-154 340mg SC | Total |
|---|---|---|---|---|---|
| Age, Continuous | 71.0 years STANDARD_DEVIATION 7.15 | 67.5 years STANDARD_DEVIATION 7.98 | 69.8 years STANDARD_DEVIATION 8.34 | 69.1 years STANDARD_DEVIATION 6.23 | 69.4 years STANDARD_DEVIATION 7.5 |
| Baseline Glucocorticoid Dose (mg/day) | 9.21 mg/day STANDARD_DEVIATION 3.801 | 9.45 mg/day STANDARD_DEVIATION 3.378 | 9.10 mg/day STANDARD_DEVIATION 3.519 | 9.52 mg/day STANDARD_DEVIATION 3.317 | 9.31 mg/day STANDARD_DEVIATION 3.495 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 42 Participants | 43 Participants | 42 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 33 Participants | 30 Participants | 25 Participants | 29 Participants | 117 Participants |
| Sex: Female, Male Male | 17 Participants | 12 Participants | 20 Participants | 15 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 42 | 0 / 45 | 0 / 44 |
| other Total, other adverse events | 27 / 50 | 25 / 42 | 30 / 45 | 37 / 44 |
| serious Total, serious adverse events | 8 / 50 | 5 / 42 | 8 / 45 | 9 / 44 |
Outcome results
Primary
Time to Flare
Flare is defined as, presence of clinical signs and symptoms of PMR and requirement to increase the glucocorticoid dose per investigator.
Time frame: From first dose of study drug to Week 52
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Flare | 113 days |
| ABBV-154, 40mg SC | Time to Flare | 225 days |
| ABBV-154, 150mg SC | Time to Flare | NA days |
| ABBV-154, 340mg SC | Time to Flare | NA days |
p-value: 0.01295% CI: [0.273, 0.878]Log Rank
p-value: 0.00495% CI: [0.248, 0.794]Log Rank
p-value: <0.00195% CI: [0.094, 0.419]Log Rank
Secondary
Change From Baseline in Glucocorticoid Dose
Change from Baseline in glucocorticoid dose.
Time frame: Week 24
Population: ITT Population with data available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glucocorticoid Dose | -4.96 mg | Standard Deviation 3.943 |
| ABBV-154, 40mg SC | Change From Baseline in Glucocorticoid Dose | -6.29 mg | Standard Deviation 3.384 |
| ABBV-154, 150mg SC | Change From Baseline in Glucocorticoid Dose | -7.40 mg | Standard Deviation 3.554 |
| ABBV-154, 340mg SC | Change From Baseline in Glucocorticoid Dose | -7.88 mg | Standard Deviation 3.398 |
p-value: 0.03995% CI: [-3.08, -0.08]ANCOVA
p-value: <0.00195% CI: [-4.15, -1.16]ANCOVA
p-value: <0.00195% CI: [-4.49, -1.52]ANCOVA
Secondary
Cumulative Glucocorticoid Dose
Cumulative glucocorticoid dose.
Time frame: Week 24
Population: ITT Population with data available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cumulative Glucocorticoid Dose | 984.576 Glucocorticoid dose (mg) | Standard Deviation 524.6579 |
| ABBV-154, 40mg SC | Cumulative Glucocorticoid Dose | 823.411 Glucocorticoid dose (mg) | Standard Deviation 397.9403 |
| ABBV-154, 150mg SC | Cumulative Glucocorticoid Dose | 734.310 Glucocorticoid dose (mg) | Standard Deviation 332.3137 |
| ABBV-154, 340mg SC | Cumulative Glucocorticoid Dose | 759.450 Glucocorticoid dose (mg) | Standard Deviation 381.1683 |
p-value: 0.14495% CI: [-208.04, 30.71]ANCOVA
p-value: 0.00795% CI: [-283.62, -45.89]ANCOVA
p-value: 0.00395% CI: [-300.52, -64.58]ANCOVA
Secondary
Percentage of Participants Achieving Flare-Free State
Percentage of participants achieving flare-free state.
Time frame: Up to Week 24
Population: ITT Population with data available for analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Flare-Free State | 11 percentage of participants |
| ABBV-154, 40mg SC | Percentage of Participants Achieving Flare-Free State | 13 percentage of participants |
| ABBV-154, 150mg SC | Percentage of Participants Achieving Flare-Free State | 15 percentage of participants |
| ABBV-154, 340mg SC | Percentage of Participants Achieving Flare-Free State | 24 percentage of participants |
p-value: 0.10795% CI: [-4, 41.4]Cochran-Mantel-Haenszel
p-value: 0.09295% CI: [-3.1, 41]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [21.4, 62.3]Cochran-Mantel-Haenszel