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

A Phase 2B Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy and Safety of 3 Dosages of SAP-001 in Combination With Standard of Care in Adult Subjects With Gout

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gout
• Intervention / Treatment: Drug: SAP-001

Detailed Description

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 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.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00907
    • Puerto Rico Site
• United States
  • California
    • Sacramento, California, United States, 95821
      • California Site
    • San Diego, California, United States, 92119
      • California Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Site
  • Florida
    • DeBary, Florida, United States, 32713
      • Florida Site
    • Miami, Florida, United States, 33173
      • Florida Site
    • Miami Lakes, Florida, United States, 33014
      • Florida Site
    • Miami Lakes, Florida, United States, 33173
      • Florida Site
    • Winter Park, Florida, United States, 32789
      • Florida Site
  • Idaho
    • Boise, Idaho, United States, 83713
      • Idaho Site
  • Maryland
    • Oxon Hill, Maryland, United States, 20745
      • Maryland Site
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Mississippi Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • North Carolina Site
  • Texas
    • Mesquite, Texas, United States, 75150
      • Texas Site
    • Plano, Texas, United States, 75093
      • Texas Site
    • The Woodlands, Texas, United States, 77832
      • Texas Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Male or female, ≥18 and ≤75 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. Already have been diagnosed with gout according to the current American College of Rheumatology (ACR) scoring criteria for the classification of primary gout; or has symptoms of gout with at least 1 of the following: i. 3 gout flares in the previous 18 months prior to screening; or ii. Presence of at least 1 gout tophus; or iii. Current diagnosis of gouty arthritis; Subject must be refractory to SoC XOI therapy, or in whom XOI is contraindicated. Refractory to SOC XOI is 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. XOI contraindication can be self-reported medical contraindication to SoC XOI therapy or in whom SoC XOI therapy is not considered medically appropriate treatment for symptomatic gout. Subject can still participate in the clinical trial if SOC XOI therapy is considered medically not appropriate or contraindicated.
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. Subjects who stopped SoC XOI therapy within 4 weeks of the Screening Visit are eligible for the study but must be restarted on SoC XOI therapy and confirmed resistant to XOI therapy (sUA levels ≥7.0 mg/dL) after at least 4 weeks of treatment.
5. Subject must have sUA levels ≥7.0 mg/dL by central laboratory results at the Screening Visit (Visit 1) and prior to randomization at the Randomization Visit (Day 1, Visit 4).

Main Exclusion Criteria:

1. Subjects not previously diagnosed as having gout before the Screening Visit.
2. Female subject is pregnant, planning to get pregnant, lactating/breastfeeding, or has a positive urine pregnancy test at the Screening Visit or prior to randomization at the Randomization Visit (Day 1, Visit 4).
3. Subject has used any prescription drugs (eg, losartan, pegloticase, URAT1 inhibitors), 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). Exceptions may be made on a case-by-case basis (such as chronic use of low dose aspirin) following discussion and agreement between the investigator and sponsor. 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.
4. 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 therapy is contraindicated or not medically appropriate) during the Run-in Period as assessed prior to randomization at the Randomization Visit (Day 1, Visit 4).
5. 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.
6. Serum creatinine level >1.5 mg/dL and/or eGFR ≤60 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation23 by central laboratory results at the Screening Visit (Visit 1) or prior to randomization at the Randomization Visit (Day 1, Visit 4).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo versus SAP-001; Placebo arm	Drug: SAP-001; Test the efficacy and safety of SAP-001 versus placebo; Other Names: Colchicine; Xanthine Oxidase Inhibitor
Experimental: SAP-001 low dose	Drug: SAP-001; Test the efficacy and safety of SAP-001 versus placebo; Other Names: Colchicine; Xanthine Oxidase Inhibitor
Experimental: SAP-001 middle dose	Drug: SAP-001; Test the efficacy and safety of SAP-001 versus placebo; Other Names: Colchicine; Xanthine Oxidase Inhibitor
Experimental: SAP-001 high dose	Drug: SAP-001; Test the efficacy and safety of SAP-001 versus placebo; Other Names: Colchicine; Xanthine Oxidase Inhibitor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanton Pharma Pte. Ltd.
• Investigators: Study Director: Carmen Arencibia, Study Official

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 12, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Hyperuricemia; Serum Uric Acid; Gout Flare
• Additional Relevant MeSH Terms: Crystal Arthropathies; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Gout; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Colchicine
• Other Study ID Numbers: SAP-001-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No