Clinical trial NCT05690204: Dose Finding Study to Evaluate Safety and Efficacy of 3 Dosages of SAP 001.
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gout
Keywords: Hyperuricemia
Serum Uric Acid
Gout Flare
Lead sponsor: Shanton Pharma Pte. Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-19
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: primary
timeFrame: 24 weeks
Secondary outcomes:
measure: AE
timeFrame: 24 weeks
measure: Change from Baseline on PE measure
timeFrame: 24 weeks
measure: Changes from Baseline on ECGs
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: California Site
state: California
city: San Diego
country: United States
facility: California Site
state: California
city: Denver
country: United States
facility: Denver Site
state: Colorado
city: DeBary
country: United States
facility: Florida Site
state: Florida
city: Miami Lakes
country: United States
facility: Florida Site
state: Florida
city: Miami Lakes
country: United States
facility: Florida Site
state: Florida
city: Miami
country: United States
facility: Florida Site
state: Florida
city: Winter Park
country: United States
facility: Florida Site
state: Florida
city: Boise
country: United States
facility: Idaho Site
state: Idaho
city: Oxon Hill
country: United States
facility: Maryland Site
state: Maryland
city: Jackson
country: United States
facility: Mississippi Site
state: Mississippi
city: Raleigh
country: United States
facility: North Carolina Site
state: North Carolina
city: Mesquite
country: United States
facility: Texas Site
state: Texas
city: Plano
country: United States
facility: Texas Site
state: Texas
city: The Woodlands
country: United States
facility: Texas Site
state: Texas
city: San Juan
country: Puerto Rico
facility: Puerto Rico Site
Study officials:
affiliation: Study Official
name: Carmen Arencibia
role: STUDY_DIRECTOR
References: