Gout, Gout Arthritis, Gout Flare
Conditions
Brief summary
This is a randomized, multicenter, double-blind, single administration study to investigate the efficacy and safety of 2 dosing regimens of Purified Cortrophin® Gel in the treatment of an acute gouty arthritis flare. The study consists of three periods: an optional pre-screening period, a double-blind treatment period, and a 7-day follow-up period. The treatment period is double-blind, and the patients will be randomized to treatment with 40 U Purified Cortrophin® Gel or 80 U Purified Cortrophin® Gel in a 1:1 ratio. Purified Cortrophin® Gel will be administered once (either subcutaneously or intramuscularly) on the first visit (Day 0; Visit 1) and surveyed after 24 hours (Day 1), 48 hours (Day 2), and 72 hours (Day 3; Visit 2) as well as on Day 7.
Interventions
DRUGPurified Cortophin Gel 80 U
This will be the 80 U dose of the purified Cortophin Gel
DRUGPurified Cortophin Gel, 40 U
This will be the 40 U dose of the purified Cortophin Gel
Sponsors
Massachusetts General Hospital
ANI Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent to participate in this study * Male and female patients, aged 18-85 years * Meeting the 2015 Gout classification criteria of the ACR/EULAR collaborative initiative * Onset of current acute gout flare within 5 days prior to study entry * Body mass index of less than or equal to 45 kg/m2 * Baseline pain intensity ≥ 50 mm on the 0-100 mm visual analog scale (VAS) * History of ≥ 1 gout flares within the 12 months prior to study entry * The patient meets at least one of the following criteria for both NSAIDs and colchicine treatment options: * Minimum of one episode of being intolerant, or unresponsive to the treatment, see Appendices 2-4. * The investigator deems the patient is either contraindicated or inappropriate for the treatment. Inappropriateness could be due to anticipated changes in patient status (i.e., such as worsening of comorbidities or use of concomitant medication), see Appendices 2-4. * Patients must be willing and capable of using an electronic device (e.g., cellphone) and must have access to a cellphone to be able to complete surveys.
Exclusion criteria
* Patients with scleroderma, osteoporosis, active or recurrent bacterial, fungal or viral infections, ocular herpes simplex, recent surgery (within 2 weeks prior to randomization or have an unhealed operation wound(s)), history of or the presence of a peptic ulcer, uncontrolled congestive heart failure, uncontrolled hypertension, uncontrolled diabetes type 1 or 2, or sensitivity to proteins derived from porcine sources. * Patients with primary adrenocortical insufficiency or adrenocortical hyperfunction. * Rheumatoid arthritis, evidence or suspicion of infectious/septic arthritis, or other acute inflammatory arthritis. * Polyarticular gouty arthritis involving more than 4 joints. * Participation in another concurrent investigational study within 30 days of randomization or has taken an investigational drug within five times the half-life of that investigational drug has passed. * Previous inclusion in this study. * Presence of severe renal function impairment: estimated creatinine clearance \<30 mL/min/1.73m2 (CKD stages 4 and 5). * Uncontrolled clinically significant hematologic, CNS, hepatic, pulmonary, gastrointestinal, metabolic, or endocrine disease as deemed by the investigator. * Presence of any medical or psychological condition or laboratory result that might create risk to the patients (or interfere with the patient's ability to comply with the protocol requirements, or to complete the study) in the opinion of the investigator. * Prior or current treatment with any ACTH product. * Pregnant or nursing (lactating) women. Women of childbearing age are required to be using an acceptable method of contraception. * Patients taking urate-lowering therapy had to be on a stable dose and regimen for ≥2 weeks before entering the study and remain on a stable dosage and regimen for at least 1 week after Purified Cortrophin® Gel. * Use of specified pain relief medications or biologics (including glucocorticoids, narcotics, paracetamol/acetaminophen, NSAIDs, colchicine, IL-blockers and tumor necrosis factor \[TNF\] inhibitors) within specified periods (see Appendix 5) prior to randomization. * Vaccination within 30 days prior to study enrollment and during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in gout pain intensity from baseline in target join to 72 hours post-injection | From baseline to Day 3/Visit 2 | Change in gout pain intensity from baseline in the target joint following PCG administration measured by Visual Analog Scale (VAS) at 72 hours post-injection (Day 3; Visit 2). Patients will score their pain intensity in the joint most affected at baseline (i.e., the index joint) on a 0-100 mm visual analogue scale (VAS), ranging from no pain (0) to unbearable pain (100). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in gout pain from baseline in target joint at Day 1 | From baseline to Day 1 | Change in gout pain intensity from baseline in the target joint following Purified Cortrophin® Gel administration measured by Visual Analog Scale (VAS) at Day 1 (24 hours post-injection). Minimum value: 0 Maximum value: 10 Higher score indicates worse outcome. |
| Change in gout pain intensity from baseline in target joint to Day 2 | From baseline to Day 2 | Change in gout pain intensity from baseline in the target joint following Purified Cortrophin® Gel administration as measured by Visual Analog Scale (VAS) at Day 2 (48 hours post-injection). Minimum value: 0 Maximum value: 10 Higher score indicates worse outcome. |
| Change in pain intensity timeline at baseline, 24 hours, 48 hours, 72 hours, and Day 7 post-injection. | From baseline to Day 7 | Change in pain intensity timeline at baseline, 24 hours, 48 hours, 72 hours, and Day 7 post-injection. |
| Time to onset of effect (≥20% change from baseline pain intensity on VAS). | From baseline to end of study (Day 7) | Time to onset of effect (≥20% change from baseline pain intensity on VAS). |
| Time to response (≥50% change from baseline pain intensity on VAS). | From baseline to end of study (Day 7) | Time to response (≥50% change from baseline pain intensity on VAS). |
| Patient Global Self-Assessment to treatment: (24 hours, 48 hours, 72 hours, and Day 7 post-injection). | From baseline to end of study (Day 7) | Patient Global Self-Assessment to treatment: (24 hours, 48 hours, 72 hours, and Day 7 post-injection). 4 - Excellent 3 - Good 2 - Acceptable 1 - Slight 0 - Poor Lower scores indicate worse outcomes. |
| Physician assessment of inflammatory signs: (baseline [Day 0; Visit 1], 72 hours [Day 3; Visit 2]) | From baseline to end of study (Day 7) | Physician assessment of inflammatory signs: (baseline \[Day 0; Visit 1\], 72 hours \[Day 3; Visit 2\]) * Physician assessment of joint tenderness 0 - No pain 1. \- Mild/patient there is pain when touched 2. \- Moderate/patient states there is pain and winces 3. \- Severe/patient states there is pain, winces and withdraws. * Physician assessment of joint swelling 0 - No swelling 1. \- Mild swelling/palpable 2. \- Moderate swelling/visible 3. \- Severe swelling/bulging beyond the joint margins * Physician assessment of erythema Absent or Present o Physician assessment of target joint range of motion 0 - Normal 1. \- Mildly restricted 2. \- Moderately restricted 3. \- Severely restricted 4. \- Immobilized The above answers will be totaled - minimum value: 0, max: 12. Higher values indicate worse outcomes. |
| Physician assessment of local tolerability at injection site (at 72 hours post-injection). | Day 3 (Visit 2) | Physician assessment of local tolerability at injection site (at 72 hours post-injection) Notes presence of redness, swelling, pain, bruising, itching (no numerical values). |
| Use of rescue medication (up to 72-hours post-injection). | From baseline to Day 3/Visit 2 | Use of rescue medication (up to 72-hours post-injection). |
| Safety assessment - AEs, SAEs | From baseline to end of study (Day 7) | Notes presence, description, duration of an AE, and whether the AE is serious. |
| Safety Assessment - Vital Signs | Day 1 Visit and Day 3 Visit | Height and Weight will be collected, and used to calculate the participant's BMI |
| Safety Assessment - Laboratory Measurements | Day 1 and Day 3 | Biochemistry: Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Total bilirubin (if \>upper limit of normal also conjugated and non-conjugated bilirubin) Alkaline phosphatase (ALP） Prothrombin Time/International Normalized Ratio (PT/INR)‡¥§ Albumin Cholesterol (total, LDL, and HDL) Triglycerides Creatinine◊§ Sodium (Na) Potassium (K) Ferritin Erythrocyte sedimentation rate Uric acid Glucose\*¥ HbA1c Troponin T C-reactive protein (CRP) Serum amyloid A (SAA) Calcium Magnesium Hematology: Hemoglobin Hematocrit White blood cells Differential blood count Thrombocytes Urine analysis: Albumin U-erythrocytes Abnormal test findings, if changed significantly from baseline will be noted. Minimum and maximum values, as well as indications of higher or lower values vary depending on the test. |
Countries
United States
Contacts
CONTACTAna D Fernandes, MA
PRINCIPAL_INVESTIGATORHyon K Choi, MD, DrPH
Massachusetts General Hospital
Outcome results
None listed