Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease

Prior treatment

• Participants not fully vaccinated for Coronavirus Disease 2019 (COVID 19).
  • Participants will be considered fully vaccinated if they have received all recommended doses of a COVID-19 vaccine that has been authorized or approved by the United States Food and Drug Administration (FDA) or is listed for emergency use by the World Health Organization within 14 days prior to the first dose of the study drug.
  • Participants who have fully recovered from COVID 19 and have a negative COVID-19 test ≥14 days before screening are eligible.
• Participants who have had acute kidney injury (AKI) within the past 3 months, or have ever received dialysis.
• Active substance abuse including inhaled or injection drugs in the year prior to screening.
• Use of cannabis or cannabinoid containing compounds within 90 days prior to screening.
• Any chronic medications started or changed within the past 3 months or at risk of needing to be changed during the study.
• Participants taking a strong inducer or inhibitor of cytochrome P450 3A4, 2D6 or 2C19 by screening. These medications are prohibited during the entire study duration.
• Having taken any investigational compound within 30 days, or 5 half-lives of the drug, whichever is longer, before the Screening Visit.

Other illness

• Significant medical condition, that in the opinion of the Investigator will place the participant at risk during the study or that will confound the study endpoints.
• Other causes of kidney disease that are not DKD (eg, lupus nephritis). Of note, hypertension is not an exclusion criteria.
• Participants with a history of epilepsy or intracranial surgery.
• Uncontrolled hypertension with measurements of systolic pressures \>160 or diastolic measurements \>100 at the Screening Visit.
• Evidence of moderate to severe hepatic impairment as defined by Child's-Pugh B or C.
• Subjects with a history of significant psychiatric disorder, including but not limited to:
  • Major depression within the last 2 years.
  • Any history of a suicide attempt or suicidal ideation.
  • Subjects with a history of other severe psychiatric disorders (eg, schizophrenia, bipolar disorder).
• Current or active malignancy within the past 5 years, except for cancer in situ, or non-melanoma skin cancer such as basal cell or squamous cell carcinoma that has been completely resected.
• Participants with a history of hyperthyroidism or other thyroid diseases.

Lab values

• Participants with an eGFR \<30 ml/min/1.73m².
• QTc \>500 msec at baseline.

Other

• Pregnancy, planned pregnancy, potential for pregnancy or unwillingness to use effective birth control during the trial, as well as breast feeding.
• Score of the 9-question Patient Health Questionnaire (PHQ-9) ≥15 at baseline.

• Male and female participants ≥18 years of age.
• Able and willing to give informed consent and to comply with scheduled visits and trial procedures.
• A diagnosis of DKD due to either T1DM or T2DM (diagnosed for ≥1 year)
• On a stable anti-diabetic medication regimen for ≥4 months prior to randomization with a hemoglobin A1C (HbA1c) \<9.5%.
  • Participants with T1DM may not be on any glucose lowering medications beyond insulin.
  • Participants with T2DM may be on more than 1 anti diabetic medication regimen (eg, SGLT2 inhibitor, insulin, or other anti-diabetic medication regimen).
  • HbA1c should have been performed within the last 4 months prior to randomization.
• Participants must be on a stable dose of ACEi or ARB for ≥4 months prior to randomization and expected to remain stable for the 4-month treatment period.
• Participants taking finerenone (not required), on a stable dose for ≥4 months prior to randomization.
• Presence of albuminuria with a UACR \>100 mg/g and \<3000 mg/g at screening.