Arthritis, Psoriatic
Conditions
Brief summary
The primary objective is to evaluate the safety and tolerability of a single intravenous dose of PG102 in patients with psoriatic arthritis. The secondary objectives are to evaluate how PG102 moves around the body and to explore its effects on the disease.
Interventions
DRUGPG102
A single intravenous infusion
DRUGPlacebo comparator
Phosphate-buffered saline
Sponsors
PanGenetics UK Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Arthritis that meets Classification of Psoriatic Arthritis (CASPAR) criteria * Plaque psoriasis for at least 6 months prior to study enrollment
Exclusion criteria
* Clinically significant psoriasis flare * Unstable doses of pain relief medication * Treatment with systemic corticosteroids other than prednisone ≤ 10 mg/day or equivalent * Treatment with any biologic therapy * Treatment with immunosuppressive agents or disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate * Treatment with lithium, any anti-malarial, chlorambucil, cyclophosphamide or therapies for psoriasis other than low potency topical corticosteroids on intertriginous and groin areas, tar or salicylate preparations on the scalp, and emollients and moisturisers * Family history of multiple thrombotic events or a personal history of any venous or arterial thrombotic event * Clinically significant result for anti-cardiolipin, Activated protein C resistance test, Protein C, Free Protein S, Antithrombin III, Factor V Leiden, Prothrombin variant, Homocysteine, Lupus anticoagulant, Prothrombin time, Activated partial thromboplastin time, Fibrinogen, Thrombin time, Factors IX and XI * Currently smoking ≥ 10 cigarettes per day or equivalent * Active tuberculosis or other infection * Current or previous malignancies * Clinically significant abnormality on physical examination, laboratory testing, vital signs or 12-lead electrocardiogram
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Reported Adverse Events | Three months | This was an exploratory study and all safety endpoints were considered. |
| The Percentage of Participants With Adverse Events | Three months | — |
| The Number of Episodes of Change in Vital Signs | Three months | Clinically significant episodes of change in blood pressure, heart rate, temperature or respiration rate on the day before dosing and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours and 4, 7, 14, 21, 28, 56 & 84 days after dosing. The investigator evaluated clinical significance primarily by blinded comparison with the respective screening value. |
| The Number of Episodes of Change in Electrocardiogram | Three months | Episodes of clinically significant change in 12-lead electrocardiogram predose,1 & 4 hours and 1 & 84 days postdose. The investigator evaluated clinical significance primarily by blinded comparison with the screening electrocardiogram. |
| The Number of Episodes of Change From Screening in Laboratory Assessments | Three months | Red cell count, haemoglobin, haematocrit, total and differential white cell counts, platelet count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, reticulocytes; urea, creatinine, urate, bilirubin, sodium, potassium, calcium, phosphate, chloride, bicarbonate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gammaglutamyl transferase, creatine phosphokinase, albumin, protein; urine pH, protein, glucose, ketones, bilirubin, blood, urobilinogen, nitrite, leucocytes, specific gravity. |
Countries
Serbia
Participant flow
Recruitment details
Eight study sites (rheumatology centres) in Serbia (3), Hungary (4) and the Russian Federation (1). The first patient's first visit was on December 2, 2008 and the last visit for the last patient was on April 21, 2010.
Pre-assignment details
The first three patients in each cohort were dosed sequentially and could not be taking methotrexate. Subsequent patients in each cohort could be dosed simultaneously and could be taking methotrexate. There was a pause between dosing the last patient in the first cohort and the first patient in the second cohort.
Participants by arm
| Arm | Count |
|---|---|
| PG102 0.3 mg/kg Lowest dose PG102 | 6 |
| PG102 1 mg/kg Second dose PG102 | 6 |
| Placebo Control, phosphate-buffered saline | 5 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Study Termination | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | PG102 0.3 mg/kg | PG102 1 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Age Continuous | 43.3 years FULL_RANGE 9.77 | 43.8 years FULL_RANGE 10.85 | 45.2 years FULL_RANGE 13.2 | 44.0 years |
| Region of Enrollment Hungary | 4 Participants | 1 Participants | 3 Participants | 8 Participants |
| Region of Enrollment Serbia | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 4 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 4 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 5 |
Outcome results
Primary
The Number of Episodes of Change From Screening in Laboratory Assessments
Red cell count, haemoglobin, haematocrit, total and differential white cell counts, platelet count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, reticulocytes; urea, creatinine, urate, bilirubin, sodium, potassium, calcium, phosphate, chloride, bicarbonate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gammaglutamyl transferase, creatine phosphokinase, albumin, protein; urine pH, protein, glucose, ketones, bilirubin, blood, urobilinogen, nitrite, leucocytes, specific gravity.
Time frame: Three months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG102 0.3 mg/kg | The Number of Episodes of Change From Screening in Laboratory Assessments | 4 Number of episodes of change |
| PG102 1 mg/kg | The Number of Episodes of Change From Screening in Laboratory Assessments | 7 Number of episodes of change |
| Placebo | The Number of Episodes of Change From Screening in Laboratory Assessments | 3 Number of episodes of change |
Primary
The Number of Episodes of Change in Electrocardiogram
Episodes of clinically significant change in 12-lead electrocardiogram predose,1 & 4 hours and 1 & 84 days postdose. The investigator evaluated clinical significance primarily by blinded comparison with the screening electrocardiogram.
Time frame: Three months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG102 0.3 mg/kg | The Number of Episodes of Change in Electrocardiogram | 0 Number of episodes of change |
| PG102 1 mg/kg | The Number of Episodes of Change in Electrocardiogram | 0 Number of episodes of change |
| Placebo | The Number of Episodes of Change in Electrocardiogram | 0 Number of episodes of change |
Primary
The Number of Episodes of Change in Vital Signs
Clinically significant episodes of change in blood pressure, heart rate, temperature or respiration rate on the day before dosing and 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours and 4, 7, 14, 21, 28, 56 & 84 days after dosing. The investigator evaluated clinical significance primarily by blinded comparison with the respective screening value.
Time frame: Three months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG102 0.3 mg/kg | The Number of Episodes of Change in Vital Signs | 0 Number of episodes of change |
| PG102 1 mg/kg | The Number of Episodes of Change in Vital Signs | 0 Number of episodes of change |
| Placebo | The Number of Episodes of Change in Vital Signs | 1 Number of episodes of change |
Primary
The Number of Reported Adverse Events
This was an exploratory study and all safety endpoints were considered.
Time frame: Three months
Population: All adverse events reported for all patients dosed were evaluated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG102 0.3 mg/kg | The Number of Reported Adverse Events | 3 Number of adverse events |
| PG102 1 mg/kg | The Number of Reported Adverse Events | 6 Number of adverse events |
| Placebo | The Number of Reported Adverse Events | 13 Number of adverse events |
Primary
The Percentage of Participants With Adverse Events
Time frame: Three months
Population: All patients dosed were evaluated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PG102 0.3 mg/kg | The Percentage of Participants With Adverse Events | 50 Percentage of Participants |
| PG102 1 mg/kg | The Percentage of Participants With Adverse Events | 67 Percentage of Participants |
| Placebo | The Percentage of Participants With Adverse Events | 40 Percentage of Participants |