Dose Finding Study to Evaluate Safety and Efficacy of 3 Dosages of SAP 001.

Study Overview
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Brief Summary
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The aim of this study is to confirm the safety and pharmacological characteristics of SAP-001, evaluate its efficacy in lowering sUA and tophus burden, and identify the appropriate dose regimen for future studies in adult subjects with gout, with or without tophi, and hyperuricemia refractory to SoC XOI therapy.

Detailed Description
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A Phase 2B, multicenter, randomized, double-blind, placebo-controlled, dose-finding study to assess the safety, PK, PD, and efficacy of 3 orally administered dosages of SAP-001 (10 mg QD, 30 mg QD, and 60 mg QD) compared to placebo QD in adult subjects with gout, with or without tophi, and hyperuricemia refractory to standard-of-care (SoC) XOI therapy. In the completed Phase 1 and Phase 2 studies, SAP-001 was well tolerated at single doses up to 120 mg and at dosages up to 60 mg QD for 28-days in subjects with gout and hyperuricemia and demonstrated statistically significant reductions in sUA levels compared to placebo. The aim of this study is to confirm the safety and pharmacological characteristics of SAP-001

Official Title
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A Phase 2B Study to Evaluate the Efficacy and Safety in Combination With Standard of Care in Adult Subjects With Gout, and Hyperuricemia Refractory to Conventional XOI Therapy

Conditions
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Gout

Intervention / Treatment
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* Drug: SAP001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and ≤65 years of age, willing and able to provide informed consent and to adhere to the requirements and guidelines of the protocol. 2. Body mass index ≥19 and ≤40 kg/m2 at the Screening Visit (Visit 1). 3. Subject must already have been diagnosed with symptomatic gout according to the current American College of Rheumatology (ACR) scoring criteria for the classification of primary gout or had symptomatic gout with at least 3 gout flares in the previous 18 months or at least 1 gout tophus or gouty arthritis, and be refractory to SoC XOI therapy as defined by a medical history of failure to normalize sUA to <6 mg/dL (the ACR target for gout) with at least 3 months of SoC XOI treatment at the maximum medically appropriate dose or a self-reported medical contraindication to SoC XOI therapy or in whom SoC XOI therapy is not considered medically appropriate treatment for symptomatic gout. 4. Subject must have been on SoC XOI therapy for gout and hyperuricemia for at least 4 weeks immediately before the Randomization Visit (Day 1, Visit 4) unless SoC XOI therapy is contraindicated or not medically appropriate. 5. Subject must have sUA levels ≥7.5 mg/dL at the Screening Visit (Visit 1) and Randomization (Day 1, Visit 4) Visits - Exclusion Criteria: Subjects not previously diagnosed as having gout before the Screening Visit. 2. Subject has used any prescription drugs (eg, losartan, pegloticase, URAT1 inhibitors), over-the-counter (OTC) medications, herbal medications or products, vitamins, or minerals that are known to lower sUA levels (except SoC XOI therapies) within 14 days prior to the Randomization Visit (Day 1, Visit 4). Subjects who are already taking losartan for blood-pressure control are allowed to enroll in the study and continue taking losartan if they have been on a stable dose for at least 6 months prior to Randomization Visit (Day 1, Visit 4). 3. Subject was not compliant with taking placebo during the Run-in Period (defined as taking <80% or >120% of planned placebo doses) or the investigator determines that the subject was not compliant with SoC XOI gout medications (unless SoC XOI SAP-001 SHANTON PHARMA PTE. LTD. Clinical Trial Protocol: SAP-001-202 Version 3.0 (Amendment 2) 10 October 2022 Confidential Page 9 of 125 therapy is contraindicated or not medically appropriate) during the Run-in Period as assessed at the Randomization Visit (Visit 4). 4. Subject had an acute gout flare (exclusive of symptomology associated with chronic synovitis/arthritis) that did not resolve at least 14 days prior to the Randomization Visit (Day 1, Visit 4). If an acute gout flare occurs during the Screening or Run-in Periods, the subject may be rescreened after a period of at least 14 days has passed following resolution of the flare. 5. Serum creatinine level >1.5 mg/dL and/or estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation by central laboratory results at the Screening Visit (Visit 1) or prior to randomization at the Randomization Visit (Day 1, Visit 4). 6. Abnormal liver function tests, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) or total bilirubin >ULN by central laboratory results at the Screening Visit (Visit 1) or prior to randomization at the Randomization Visit (Day 1, Visit 4). Subjects with a history of Gilbert's syndrome may be enrolled if total bilirubin <2 × ULN by central laboratory results at the Screening Visit (Visit 1) and prior to randomization at the Randomization Visit (Day 1, Visit 4). 7. Subjects diagnosed with acute liver disease within 2 years prior to the Screening Visit (Visit 1). 8. Subjects previously diagnosed with chronic liver disease or hepatic insufficiency before the Screening Visit (Visit 1). 9. Subjects with a current or history of suspected hepatic steatosis (fatty liver) Historical liver ultrasound may be used to evaluate hepatic steatosis -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo versus SAP 001<br>Placebo arm | Drug: SAP001<br>* Test the efficacy and safety of SAP 001 versus placebo<br>* Other names: Colchicine;|
| Experimental: SAP001 10 mg<br>SAP001 10 mg | Drug: SAP001<br>* Test the efficacy and safety of SAP 001 versus placebo<br>* Other names: Colchicine;|
| Experimental: SAP001 30 mg<br>SAP001 30mg | Drug: SAP001<br>* Test the efficacy and safety of SAP 001 versus placebo<br>* Other names: Colchicine;|
| Experimental: SAP001 60 mg<br>SAP001 60 mg | Drug: SAP001<br>* Test the efficacy and safety of SAP 001 versus placebo<br>* Other names: Colchicine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| primary | assess the proportion of subjects who achieved sUA levels less than 6 mg/dl by laboratory results | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE | Incidence of AEs including SAE and TEAEs by CTCAE criteria | 24 weeks | 
| Change from Baseline on PE measure | Changes from baseline in Physical Exam based on number of participants with abnormal findings | 24 weeks | 
| Changes from Baseline on ECGs | Changes from baseline in ECG parameters by QTc intervals | 24 weeks |