Clinical trial NCT05514548: Phase 2 Study of INV-202 in Patients With Diabetic Kidney Disease
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of the Efficacy, Safety, and Pharmacokinetics of Two Doses of INV-202 in Patients With Diabetic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Kidney Disease
Keywords: Diabetic Kidney Disease
Type 1 diabetes mellitus (T1DM)
Type 2 diabetes mellitus (T2DM)
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2022-08-24
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to assess the efficacy, safety, tolerability, and transformation within the human body of INV-202 investigational drug in the treatment of adult participants with a diagnosis of Diabetic Kidney Disease due to either Type 1 diabetes mellitus or Type 2 diabetes mellitus.

Detailed description: This is a Phase 2, randomized, double-blind, placebo controlled, dose ranging, multicenter study designed to assess the efficacy, safety, tolerability, and pharmacokinetics of INV-202 for the treatment of adult participants with a diagnosis of DKD due to either Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM) (diagnosed ≥1 year) who are on a stable anti diabetic medication regimen for ≥4 months prior with a HbA1c \<9.5%. Approximately 240 participants (80/arm) will be randomized to 1 of 3 treatment arms in a 1:1:1 ratio: INV 202 10 mg, INV-202 25 mg, or placebo. The assigned study treatment will be taken once daily (QD), for 16 weeks.

Due to the high expected screen failure rates, participants may be pre-screened at sites with an approved pre-screening ICF.

Each participant will be allowed 1 retest during the screening period if they fail screening and 1 re-screening on a case by case basis with approval from the Worldwide medical monitors.

Study participation will last approximately 22 weeks and includes a Screening Period (up to 4 weeks), a Study Treatment Period with 16 weeks of daily study treatment, and a Safety Follow-Up Visit consisting of a phone call 2 weeks after the End of Treatment Visit (Week \[W\]18) to allow reporting of any adverse events following withdrawal of the study drug.

Any participant who withdraws before completing treatment will be requested to return for an Early Termination Visit, at which time the procedures normally scheduled for the W16 visit will be conducted.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants ≥18 years of age.
2. Able and willing to give informed consent and to comply with scheduled visits and trial procedures.
3. A diagnosis of DKD due to either T1DM or T2DM (diagnosed for ≥1 year)
4. On a stable anti-diabetic medication regimen for ≥4 months prior to randomization with a hemoglobin A1C (HbA1c) \<9.5%.

   1. Participants with T1DM may not be on any glucose lowering medications beyond insulin.
   2. Participants with T2DM may be on more than 1 anti diabetic medication regimen (eg, SGLT2 inhibitor, insulin, or other anti-diabetic medication regimen).
   3. HbA1c should have been performed within the last 4 months prior to randomization.
5. 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.
6. Participants taking finerenone (not required), on a stable dose for ≥4 months prior to randomization.
7. Presence of albuminuria with a UACR \>100 mg/g and \<3000 mg/g at screening.

Exclusion Criteria:

1. 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.
2. Participants not fully vaccinated for Coronavirus Disease 2019 (COVID 19).

   1. 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.
   2. Participants who have fully recovered from COVID 19 and have a negative COVID-19 test ≥14 days before screening are eligible.
3. Other causes of kidney disease that are not DKD (eg, lupus nephritis). Of note, hypertension is not an exclusion criteria.
4. Participants with an eGFR \<30 ml/min/1.73m².
5. Participants who have had acute kidney injury (AKI) within the past 3 months, or have ever received dialysis.
6. Participants with a history of epilepsy or intracranial surgery.
7. Uncontrolled hypertension with measurements of systolic pressures \>160 or diastolic measurements \>100 at the Screening Visit.
8. Active substance abuse including inhaled or injection drugs in the year prior to screening.
9. Use of cannabis or cannabinoid containing compounds within 90 days prior to screening.
10. Pregnancy, planned pregnancy, potential for pregnancy or unwillingness to use effective birth control during the trial, as well as breast feeding.
11. Evidence of moderate to severe hepatic impairment as defined by Child's-Pugh B or C.
12. Subjects with a history of significant psychiatric disorder, including but not limited to:

    1. Major depression within the last 2 years.
    2. Any history of a suicide attempt or suicidal ideation.
    3. Subjects with a history of other severe psychiatric disorders (eg, schizophrenia, bipolar disorder).
13. Score of the 9-question Patient Health Questionnaire (PHQ-9) ≥15 at baseline.
14. 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.
15. QTc \>500 msec at baseline.
16. Any chronic medications started or changed within the past 3 months or at risk of needing to be changed during the study.
17. Participants with a history of hyperthyroidism or other thyroid diseases.
18. 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.
19. Having taken any investigational compound within 30 days, or 5 half-lives of the drug, whichever is longer, before the Screening Visit.

Primary outcomes:
measure: Change in UACR from baseline to W16
timeFrame: 16 weeks
Secondary outcomes:
measure: Change in urine protein to creatinine ratio (UPCR) from baseline to W16
timeFrame: 16 weeks
measure: Change in eGFR using serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula from baseline to W16
timeFrame: 16 weeks
measure: Change in eGFR using cystatin C and the CKD-EPI formula from baseline to W16
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Garden Grove
country: United States
facility: National Institute of Clinical Research, Inc.
state: California
city: Pomona
country: United States
facility: National Institute of Clinical Research, Inc - Pomona
state: California
city: Salinas
country: United States
facility: Central Coast Nephrology
state: California
city: San Dimas
country: United States
facility: North American Research Institute
state: California
city: Upland
country: United States
facility: National Institute of Clinical Research, Inc - Upland
state: California
city: Boca Raton
country: United States
facility: Research Physicians Network Alliance
state: Florida
city: Cooper City
country: United States
facility: ALL Medical Research, LLC
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Rockville
country: United States
facility: Endocrine and metabolic Consultants
state: Maryland
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center, Inc
state: Nevada
city: Greenville
country: United States
facility: Physicians East, PA
state: North Carolina
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center
state: Pennsylvania
city: Orangeburg
country: United States
facility: South Carolina Clinical Research LLC
state: South Carolina
city: Knoxville
country: United States
facility: Knoxville Kidney Center, Pllc
state: Tennessee
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, LLC
state: Texas
city: Pearland
country: United States
facility: Linq Research, LLC
state: Texas
city: Pearland
country: United States
facility: Linq Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Laval
country: Canada
facility: Centre de recherche Clinique de Laval
state: Quebec
city: Montreal
country: Canada
facility: GCP Research
state: Quebec
city: Kutaisi
country: Georgia
facility: "Clinic- LJ", LTD
city: Rust'avi
country: Georgia
facility: LTD Clinic Rustavi
city: Tbilisi
country: Georgia
facility: L. Managadze National Center of Urology, LTD
city: Tbilisi
country: Georgia
facility: Acad. G. Chapidze Emergency Cardiology Center LTD, Department of Internal Medicine and Medical Research
city: Tbilisi
country: Georgia
facility: Acad. G. Chapidze Emergency Cardiology Center LTD, Department of Multi-center Clinical Trials
city: Tbilisi
country: Georgia
facility: Archangel St Michael Multiprofile Clinical Hospital Ltd
city: Tbilisi
country: Georgia
facility: Ltd "Institute of Clinical Cardiology"
city: Tbilisi
country: Georgia
facility: Tbilisi Heart and Vascular Clinic LTD
city: Tbilisi
country: Georgia
facility: Georgian Dutch Hospital LLC
city: Tbilisi
country: Georgia
facility: LTD Tbilisi Heart Center
city: Tbilisi
country: Georgia
facility: Aleksandre Aladashvili Clinic LLC
city: Tbilisi
country: Georgia
facility: Israel-Georgia Research Clinic Helsicore, LTD
city: Tbilisi
country: Georgia
facility: LTD "Adapt"
city: Tbilisi
country: Georgia
facility: National Institute of Endocrinology, LTD,
city: Baja
country: Hungary
facility: Diaverum Dialysis Centre of Baja and Nephrology Out-Patient Clinic of Baja St.Rokus Hospital
city: Budapest
country: Hungary
facility: DPC Hospital - Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, 1st Department of Internal Medicine
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Kistarcsa
country: Hungary
facility: Flor Ferenc Hospital of Pest County
city: Nyíregyháza
country: Hungary
facility: Medifarma-98 Kft
city: Afula
country: Israel
facility: Haemek medical center
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus \ Rambam Medical Center
city: H̱olon
country: Israel
facility: Wolfson medical center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Beilinson Campus
city: Safed
country: Israel
facility: Ziv Medical Center - Endocrinology Clinic
city: Safed
country: Israel
facility: Ziv Medical Center
city: Cuernavaca
country: Mexico
facility: Instituto de Diabetes Obesidad Y Nutricion , S.C.
city: Guadalajara
country: Mexico
facility: Centro de Investigación Médica y Reumatología S.C.
city: Guadalajara
country: Mexico
facility: Cento de Investigacion Medica de Occidente, S.C.
city: Guadalajara
country: Mexico
facility: Cento de Investigacion Medica de Occidente, S.C.
city: Guadalajara
country: Mexico
facility: Medical Office
city: Guadalajara
country: Mexico
facility: Unidad de Investigación Clinica y atencion Medica HEPA
city: Mexico City
country: Mexico
facility: Clinica Integral del Paciente Diabético y Obeso
city: Mérida
country: Mexico
facility: Investigación Médica
city: Mérida
country: Mexico
facility: St Lucas Clinical Research Center SA de CV
city: Veracruz
country: Mexico
facility: Instituto Veracruzano en Investigacion Clínica S.C.
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun
city: Belgrade
country: Serbia
facility: General Hospital "Vršac"
city: Belgrade
country: Serbia
facility: University Clincial Center of Serbia
city: Kragujevac
country: Serbia
facility: University of Kragujevac - Klinicki Centar "Kragujevac"
city: Kruševac
country: Serbia
facility: General Hospital Krusevac
city: Niš
country: Serbia
facility: University Clinical Center Nis, Clinic of Nephrology
city: Novi Sad
country: Serbia
facility: University Clinical Center of Vojvodina
city: Užice
country: Serbia
facility: Healt Center Uzice,General Hospital
city: Zaječar
country: Serbia
facility: Health Center Zajecar
Study officials:
affiliation: Inversago Pharma
name: Glenn Crater, MD
role: STUDY_DIRECTOR
References: