Clinical Research

Venglustat in Subjects With ADPKD

Sponsored by: Genzyme, a Sanofi Company

Primary Objective:

To determine the effect of venglustat on the rate of total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline in patients at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD).

Secondary Objectives:

  • To determine the effect of venglustat on the rate of renal function decline (Stage 1) and on the rate of TKV growth (Stage 2).
  • To evaluate the pharmacokinetics (PK) of venglustat in Autosomal Dominant Polycystic Kidney Disease patients (Stages 1 and 2).
  • Safety/tolerability objective:
  • To characterize the safety profile of venglustat (Stages 1 and 2).
  • To evaluate the effect of venglustat on mood using Beck Depression Inventory II (BDI-II) (Stages 1 and 2).
  • To evaluate the effect of venglustat on the lens by ophthalmological examination (Stages 1 and 2).
  • To evaluate change in nocturia based on patient reported diary (Stages 1 and 2).
  • To evaluate the effect of venglustat on kidney concentrating ability by assessing urine osmolality (in patients not on diuretic) (Stage 2 only).

 

Who can participate?

You may be able to join the study if you have:

  • Male or female adult with Autosomal Dominant Polycystic Kidney Disease (ADPKD) with age at the time the consent is signed:

    1. between 18 to 50 years (both inclusive) for patients from Stage 1
    2. between 18 to 50 years (both inclusive) for patients from Stage 2 with eGFR between 45 and 89.9 mL/min/1.73 m2 during screening period*
    3. between 18 to 55 years (both inclusive) for patients from Stage 2 with eGFR between 30 and 44.9 mL/min/1.73 m2 during screening period.*
  • Diagnosis of AKPKD in patients with a family history will be based on unified Pei criteria.
  • Stable treatment regimen of anti-hypertensive therapy for at least 30 days prior to the screening visit for hypertensive patient.
  • Patient does not have access to tolvaptan at the time of study start or tolvaptan is not indicated for treatment of patient according to treating physician
  • Female patients of childbearing potential and male patients must agree to practice true abstinence in line with their preferred and usual lifestyle or to use double-contraceptive methods (including a highly effective method of contraception for female participants of childbearing potential) for the entire duration of the study and for at least 6 weeks for females and 90 days for males following their last dose of study drug.

 

What will happen during the study?

If you are eligible and agree to participate in the study, you will be required to:

  • Visit the study clinic up to 13 times

  • Have MRI, Ocular exam, and ECG procedures

  • Take the investigational medication daily as directed by the study doctor

  • Have blood and urine tests

  • Drink enough fluids (a minimum of 8 to 12 glasses during the day)

Enrollment is now open.

For more information: visit https://clinicaltrials.ucsf.edu/trial/NCT03523728 and https://clinicaltrials.gov/ct2/show/NCT03523728

You may also contact [email protected] or Julie Yeh at [email protected] or 415-502-3618.

___________________________________________________________________________________________________________________________________________________________

Bardoxolone Methyl in Subjects With ADPKD

Sponsored by: Reata Pharmaceuticals, Inc.

This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD.

Patients will be randomized 1:1 to either bardoxolone methyl or placebo. Patients receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Dose de-escalation is permitted during the study if indicated clinically, and subsequent dose re-escalation is also permitted to meet the dosing objective of the highest tolerated dose.

All patients in the study will follow the same visit and assessment schedule. Following randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 and by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they received at Week 48 and will continue study drug treatment through Week 100. Patients will also be scheduled to be assessed at an in-person follow-up visit at Week 104, four weeks after the end of treatment.

 

Who can participate?

You may be able to join the study if you have:

  • Male and female patients 18 ≤ age ≤ 70 upon study consent
  • Diagnosis of ADPKD by modified Pei-Ravine criteria: 1) at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or 2) at least 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history
  • Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 30 to≤ 90 mL/min/1.73 m2 (18 to 55 years) or ≥ 30 to ≤ 44 mL/min/1.73 m2 (56 to 70 years)
  • 1) Patients with either screening eGFR ≥ 60 to ≤ 90 mL/min/1.73 m2 or age 56 to 70 years, must have evidence of ADPKD progression (i.e., eGFR decline of ≥ 2.0 mL/min/1.73 m2 per year, based on historical eGFR data and medical monitor discretion)

     2)The two eGFR values collected at Screen A and Screen B visits used to determine eligibility must have a percent difference ≤ 25%

  • Albumin to creatinine ratio (ACR) ≤ 2500 mg/g at Screen B visit
  • Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 80 mmHg at Screen A visit after a period of rest. Patients receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) must be on a stable dose for at least 6 weeks prior to the Screen A visit.

 

What will happen during the study?

If you are eligible and agree to participate in the study, you will be required to:

  • Visit the study clinic up to 18 times

  • Have Kidney Ultrasound, Echocardiogram, and ECG procedures

  • Take the investigational medication daily as directed by the study doctor

  • Have blood and urine tests

  • Drink enough fluids (a minimum of 8 to 12 glasses during the day)

Enrollment is now open.

For more information: visit https://clinicaltrials.ucsf.edu/trial/NCT03918447 and https://clinicaltrials.gov/ct2/show/NCT03918447

You may also contact [email protected] or Julie Yeh at [email protected] or 415-502-3618.

___________________________________________________________________________________________________________________________________________________________

Tesevatinib in Subjects With ADPKD

Sponsored by: Kadmon Corporation, LLC

The goal of the study is to compare and evaluate safety and efficacy of tesevatinib 50mg versus placebo in patients with ADPKD.

Safety and efficacy of 50mg tesevatinib in comparison to placebo in patients with autosomal dominant polycystic kidney disease (ADPKD) will be assessed.

The primary purpose of this study is focused on evaluating the change from baseline in height-adjusted total kidney volume (htTKV) as measured by magnetic resonance imaging (MRI) at Months 12, 18, and 24 in patients with ADPKD treated with tesevatinib or placebo.

If eligible for the study participation, subjects will be randomly assigned to either investigational treatment group or placebo group. Treatment group will receive 50mg tesevatinib once daily for 24 months and control group will receive the placebo once daily for 24 months.

 

Who can participate?

You may be able to join the study if you have:

  • ADPKD diagnosis based on Ravine's criteria
  • Cysts of at least 1 cm
  • eGFR ≥ 30 mL/min/1.73 m2 and ≤ 80 mL/min/1.73 m2, using the Modification of Diet in Renal Disease-4 variable formula
  • htTKV

 ≥ 500 mL for subjects 18-35 years of age
 ≥ 750 mL for subjects 36-49 years of age
 ≥ 900 mL for subjects 50-60 years of age

  • Have the following laboratory values:

Platelets > lower limit of normal (LLN), Hemoglobin > 9 g/dL, Total bilirubin ≤ 1.5 mg/dL, Aspartate aminotransferase (AST) < 2.5 × upper limit of normal (ULN), Alanine aminotransferase (ALT) < 2.5 × ULN, Prothrombin time/partial thromboplastin time ≤ 1.5 × ULN, Serum potassium levels within normal limits, Serum magnesium levels within normal limits, Albumin ≥ LLN, Amylase ≤ 1.5 x ULN , Lipase ≤ 1.5 x ULN, Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 × ULN, International normalized ratio (INR) ≤ 1.5, except those subjects taking warfarin who must have INR ≤ 3

  • Female subjects of childbearing potential with negative pregnancy test at screening
  • If sexually active, the subject agrees to use 2 accepted methods of contraception during the course of the study and for 6 months after their last dose of study drug

 

What will happen during the study?

If you are eligible and agree to participate in the study, you will be required to:

  • Visit the study clinic up to 23 times

  • Have MRI, Echocardiogram, Ocular exam, and ECG procedures

  • Take the investigational medication daily as directed by the study doctor

  • Have blood and urine tests

  • Drink enough fluids (a minimum of 8 to 12 glasses during the day)

Enrollment is now close.

For more information: visit https://clinicaltrials.ucsf.edu/trial/NCT03203642 and https://clinicaltrials.gov/ct2/show/NCT03203642

You may also contact [email protected] or Julie Yeh at [email protected] or 415-502-3618.