A Dose Escalation Study of IG3018 in Subjects With Hyperuricemia With or Without Chronic Kidney Disease

A Dose Escalation Study of IG3018 to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics in Subjects With Hyperuricemia With or Without Chronic Kidney Disease

This is a phase I/II clinical study to evaluate the safety, tolerability, PK, and efficacy of IG3018 tablet in hyperuricemia (HUA) subjects with or without CKD.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperuricemia; Hypouricemia, Renal
• Intervention / Treatment: Drug: IG3018; Other: Placebo matching IG3018

Detailed Description

The study has two parts:

Part 1 is a randomized, double-blind, placebo-controlled, dose escalation study in hyperuricemia subjects without CKD. Initiation Dose shall be at 0.25 g tablets (Cohort A) and doses are escalated to 0.5 g (Cohort B) and then to 1.0 g (Cohort C) in a planned manner.

Part 2 is an open-label, proof of concept study involving hyperuricemia subjects with advanced predialysis CKD (Stage 3a, Stage 3b and Stage 4), and treated with two doses [0.5 g BID IG3018 (Cohort D) and 1.0 g BID IG3018 (Cohort E)].

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Feng Yan; Phone Number: +86 18612826692; Email: yan.feng@intelligemtx.com
• Study Contact Backup: Name: Maoduan Du; Phone Number: +86 13910863795; Email: du.maoduan@intelligemtx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For Part 1 and Part 2:

Subjects must meet all the following criteria to be included in the study:

1. Male or female, aged 18 to 75 years (both inclusive).

2. According to the investigator's judgment, eGFR must be met as:

   Part 1 only, subjects without CKD and have eGFR ≥ 60 mL/minute/1.73 m2 at screening phase; Part 2 only, subjects with CKD (Stage 3a, 3b and Stage 4) have eGFR≥15 and <60 mL/minute/1.73 m2 at screening phase.

3. The serum uric acid level for subjects need to meet any of the following:

   For subjects already on ULT within 2 weeks prior to the screening visit, the serum uric acid would be measured during the screening visit/phase, and then at the end of the run-in phase, prior to confirming their eligibility. Subjects with ULT within 2 weeks before screening has fasting serum uric acid ≥ 0.48 mmol/L at the end of run-in phase.

   For subjects without ULT in 2 weeks prior to screening visit，the serum uric acid should be measured twice on 2 different days (at least 24 hours apart) prior to confirming their eligibility. Subjects without ULT within 2 weeks before screening has fasting serum uric acid ≥ 0.48 mmol/L at screening phase.

4. Body Mass Index (BMI) ≥ 18 and ≤ 35 kg/m2 (both inclusive) at screening.
5. Female subjects of child-bearing potential must agree to use highly effective contraceptive methods and must abstain from egg collection or donation from the screening phase to 90 days after the last dose of the study drug. And the male partner of a female subject also needs to agree to use highly effective method of birth control during this phase (Appendix 1).
6. Male subjects considered fertile must agree to not donate sperm, and take effective contraceptive methods from the screening phase to 90 days after the last dose of the study drug. And the female partner of male subjects also needs to agree to use a highly effective method of female contraception during this phase (Appendix 1).
7. Able to understand and give signed written informed consent form and willing to comply with all study procedures.

Exclusion Criteria:

For Part 1 and Part 2:

Subjects who meet any of the following criteria will be excluded from the study:

1. Prior uricase therapy or exposure to recombinant uricase, such as Rasburicase or Pegloticase.
2. Subject has acute gout flares requiring treatment within 3 months prior to or during Screening.
3. Major surgery within 3 months prior to the first administration.
4. History of malignant tumors within 6 months prior to screening.
5. Subject within the last 3 months has: myocardial infarction, angina, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemia attack.
6. Subject who are on taking any other urate-lowering medication (allopurinol, febuxostat, probenecid and benzbromarone) and cannot stop during the study periods included in the run-in phase.
7. Subject with underlying medical conditions requiring changes or introduction of drugs that have the potential impact on the serum uric acid levels (e.g., salicylic acids, diuretics, angiotensin receptor blockers, etc.) within at least 1 month prior the screening phase.
8. History of gastrointestinal (GI) surgery, including gastric sleeve, colostomy/ enterostomy, Roux-en-Y or gastric banding (unless gastric band removed for a minimum of 12 months prior to Screening.
9. History of GI diseases, including gastrointestinal bleeding moderate to severe gastrointestinal dysfunction, moderate to severe chronic constipation for a minimum of 3 months prior to screening, or newly diagnosed peptic or duodenal ulcer diseases within 4 weeks prior to screening.
10. Inability to swallow oral medications.
11. Received treatment with or exposure to an Investigational drug or device within 30 days of signing informed consent.
12. Subject with one of positive results of HIV virus, or positive hepatitis B virus surface antigen (HBsAg) and the number of copies of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) at screening, or HBsAg (-), hepatitis B core antibody (HBcAb) (+) and the number of copies of HBV DNA ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) after treatment of HBV infection, or positive hepatitis C antibody (HCV-Ab), and hepatitis C virus (HCV) ribonucleic acid (RNA) ≥ ULN of the study site during Screening phase.
13. History of alcohol abuse, or subjects who consumed alcohol within 48 h before the first administration or did not agree to stop using alcohol products during the study.
14. Subject who has previously been diagnosed with the following diseases and has not been able to control them after medication therapy or other treatment. Uncontrolled is defined as hypertension: msSBP ≥ 180mmHg and/or msDBP ≥ 110mmHg; or Diabetes mellitus: HbA1c ≥ 9% at screening.
15. Subject with secondary hyperuricemia caused by tumor, hematological system diseases, drugs, etc. except for chronic kidney disease; or hereditary hyperuricemia at screening.
16. Subjects undergoing kidney transplantation or planning to undergo kidney transplantation at screening.
17. History of serious hypersensitivity reaction to a known ingredient of IG3018 tablet judged by the investigator.
18. Subject who is considered unsuitable for participating in the study in the opinion of the investigator judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A (0.25 g tablets); Cohort A will have 10 eligible patients. 8 subjects will receive the active study drug (IG3018) and 2 shall receive placebo in each dose cohort. Dose shall be at 0.25 g tablets. Single-dose initial treatment phase: D1~D3. Subject will receive a single dose of IG3018 or the placebo on Day 1. The predetermined information shall be collected in the form of blood and urine samples for PK analyses, whilst efficacy and safety assessment data will be collected within 48 hours after the single dose of study drug administration (IG3018 or placebo). Maintenance treatment on daily basis phase: 4 weeks. Subjects in this maintenance treatment phase shall receive the study drug IG3018 in twice daily dosing for 28 days from Day 4 to Day 31, and will be given IG3018 once on the morning of D32.	Drug: IG3018; Oral administration; Other: Placebo matching IG3018; Oral administration
Other: Cohort B (0.5 g tablets); Cohort B will have 10 eligible patients. 8 subjects will receive the active study drug (IG3018) and 2 shall receive placebo in each dose cohort. Dose shall be at 0.5 g tablets. Single-dose initial treatment phase: D1~D3. Subject will receive a single dose of IG3018 or the placebo on Day 1. The predetermined information shall be collected in the form of blood and urine samples for PK analyses, whilst efficacy and safety assessment data will be collected within 48 hours after the single dose of study drug administration (IG3018 or placebo). Maintenance treatment on daily basis phase: 4 weeks. Subjects in this maintenance treatment phase shall receive the study drug IG3018 in twice daily dosing for 28 days from Day 4 to Day 31, and will be given IG3018 once on the morning of D32.	Drug: IG3018; Oral administration; Other: Placebo matching IG3018; Oral administration
Other: Cohort C (1.0 g tablets); Cohort C will have 10 eligible patients. 8 subjects will receive the active study drug (IG3018) and 2 shall receive placebo in each dose cohort. Dose shall be at 1.0 g tablets. Single-dose initial treatment phase: D1~D3. Subject will receive a single dose of IG3018 or the placebo on Day 1. The predetermined information shall be collected in the form of blood and urine samples for PK analyses, whilst efficacy and safety assessment data will be collected within 48 hours after the single dose of study drug administration (IG3018 or placebo). Maintenance treatment on daily basis phase: 4 weeks. Subjects in this maintenance treatment phase shall receive the study drug IG3018 in twice daily dosing for 28 days from Day 4 to Day 31, and will be given IG3018 once on the morning of D32.	Drug: IG3018; Oral administration; Other: Placebo matching IG3018; Oral administration
Other: Cohort D (0.5 g BID IG3018); 5 to 8 hyperuricemia subjects with advanced CKD will be enrolled in Cohort D and will receive 0.5 g IG3018 twice daily (BID) for 4 weeks.	Drug: IG3018; Oral administration
Other: Cohort E (1.0 g BID IG3018); 5 to 8 hyperuricemia subjects with advanced CKD will be enrolled in Cohort E and will receive 1.0 g IG3018 twice daily (BID) for 4 weeks.	Drug: IG3018; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessments (Part 1 and Part 2)	Safety as assessed by incidence of reported adverse events, clinically significant changes in vital signs, physical examination, laboratory tests, 12-lead ECG. Safety as assessed by incidence of AEs by using the Common Terminology Criteria for Adverse Events, Version 5 (CTCAEv5).	Baseline through study completion at up to 46 days
The proportions of change from baseline in serum uric acid to normal level (≤ 0.36 mmol/L) (Part 1 and Part 2)	The proportions of change from baseline in serum uric acid to normal level (≤ 0.36 mmol/L) following 4 weeks treatment with IG3018 in each dose.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportions of change from baseline in serum uric acid to ≤ 0.30 mmol/L and ≤ 0.24 mmol/L respectively (Part 1 and Part 2)	The proportions of change from baseline in serum uric acid to ≤ 0.30 mmol/L and ≤ 0.24 mmol/L respectively, following 4 weeks treatment with IG3018 in each dose.	4 weeks
The actual change of serum uric acid (Part 1 and Part 2)	The actual change of serum uric acid from baseline to the end of 1, 2, 3, and 4 weeks of each treatment group.	4 weeks
The percentage change of serum uric acid (Part 1 and Part 2)	The percentage change of serum uric acid from baseline to the end of 1, 2, 3, and 4 weeks of each treatment group.	4 weeks
Gouty Attacks (Part 1 and Part 2)	Incidence of reported gouty attacks during the study period.	Baseline through study completion at up to 46 days
Urinary Albumin/Creatinine Ration (U-ACR) (Part 2 only)	The change in Urinary Albumin/Creatinine ration (U-ACR) during the study period.	Baseline through study completion at up to 43 days
Ae of IG3018 (Part 1 only)	Urine Accumulative excretion (Ae) of IG3018	32 days
Cmax of IG3018 (Part 1 only)	Maximum observed plasma concentration of IG3018	46 days
Tmax of IG3018 (Part 1 only)	Time to reach maximum plasma concentration of IG3018	46 days
T1/2 of IG3018 (Part 1 only)	Terminal half-life of IG3018	46 days

Collaborators and Investigators

• Sponsor: Intelligem Therapeutics Australia Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 3, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; Hyperuricemia; Hyperuricemia, Renal; Hyperuricemia, CKD
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hyperuricemia
• Other Study ID Numbers: IG3018-23-02-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No