Multicenter, Randomized, Double-blind, Placebo-controlled Two Stage Study to Characterize the Efficacy, Safety, Tolerability and Pharmacokinetics of GZ/SAR402671 in Patients at risk of Rapidly Progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- Conditions
- ADPKDkidney disease10038430
- Registration Number
- NL-OMON50604
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 32
- Male or female adult with ADPKD:
a) between ages of 18 and 50 years (inclusive) for patients in Stage 1
b) between 18 and 50 years (inclusive) for patients in Stage 2 with an eGFR
between 45 and 89.9 mL/min/1.73 m2 during the screening period
c) between 18 and 55 years (inclusive) for patients in Stage 2 with an eGFR
between 30 and 44.9 mL/min/1.73 m2 during the screening period
Diagnosis of ADPKD in patients with a family history, will be based on unified
Pei criteria. In the absence of a family history, the diagnosis will be based
on the presence of renal cysts bilaterally, totaling at least 20, in the
absence of findings suggestive of other cystic renal diseases.
- Mayo Imaging Classification of ADPKD Class 1C, 1D or 1E.
- Estimated glomerular filtration rate between 45 to 89,9 mL/min/1.73 m2 during
the screening period (Chronic Kidney Disease Epidemiology Collaboration
[CKD-EPI]) for stage 1.
- Estimated glomerular filtration rate between 30 and 89.9 mL/min/1.73 m2
during the
screening period (CKD-EPI equation) for Stage 2.
- Stable treatment regimen of antihypertensive therapy for at least 30 days
prior to the screening visit for hypertensive patient.
- Able to read, comprehend, and respond to the study questionnaires.
- Patient has given voluntary written informed consent before performance of
any study related procedures not part of standard medical care.
- 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 (patient does not meet recommended criteria for treatment or does not
tolerate treatment with tolvaptan).
- The patient, if female of childbearing potential, must have a negative blood
pregnancy test (*-human chorionic gonadotropin [*-hCG]) at the screening visit
and a negative urine pregnancy test at the baseline visit.
- 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
- Systolic BP >160 mmHg at run-in and baseline visits.
- History of administration of tolvaptan or other Polycystic Kidney
Disease-modifying agents (somatostatin analogues) within 3 months prior to the
screening visit.
- The patient, in the opinion of the Investigator, is unable to adhere to the
requirements of the study or unable to undergo study assessments (eg, has
contraindications to pupillary dilation or unable to undergo magnetic resonance
imaging [MRI] [For example: patient*s weight exceeds weight capacity of the
MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia,
large abdominal/back tattoos, etc]).
- Current participation in another investigational interventional study or use
of investigational medicinal product (IMP), within 3 months or 5 half-lives,
whichever is longer, before randomization.
- The patient has a positive result of any of the following tests: hepatitis B
surface antigen [HBsAg], anti-hepatitis C virus [anti-HCV] antibodies,
anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2
Ab). Patients with a positive hepatitis B surface antibody (HBsAb) test are
eligible if other criteria are met (ie, negative tests for: HBsAg, hepatitis B
core antibody [HBcAb], and hepatitis C virus antibody [HCVAb]). Patients immune
due to natural infection (positive HBsAb, negative HBsAg, positive HBcAb) are
eligible if they have a negative HBV DNA test.
- A history of drug and/or alcohol abuse within the past year prior to the
screening visit.
- A history of alcohol dependence within the 5 years prior to the screening
visit.
- Any patient who is the Investigator or any Subinvestigator, research
assistant, pharmacist, study coordinator, other staff, or relative thereof
directly involved in the conduct of the study.
- The patient is scheduled for in-patient hospitalization including elective
surgery, during the
study.
- The patient has a clinically significant, uncontrolled medical condition
that, in the opinion of the investigator, would put the safety of the subject
at risk through participation, or which would affect the efficacy or safety
analysis if the condition exacerbated during the study, or that may
significantly interfere with study compliance, including all prescribed
evaluations and follow-up activities.
The list of medical conditions that should be taken into account includes, but
is not limited
to the following:
Congestive heart failure New York Heart Association (NYHA) Grade III/IV),
clinically significant cardiac arrhythmia, severe unstable angina pectoris
within 6 months of Visit 1, hypertensive
emergency within 6 months of Visit 1, stroke or transient ischemic attack
within 3 months of Visit 1, myocardial infarction within 3 months of Visit 1,
current malignancy, tuberculosis (current or untreated), Cushing's disease,
Addison's disease, uncontrolled diabetes mellitus, uncontrolled thyroid disorder
- Any country-related specific regulation that would prevent the patient from
entering the
study.
- The patients did not adhere to treatment (<70% compliance rate) in the run-in.
- The patient has, according to World Health Organization (WHO) Grading (13), a
cortical cataract *1-quarter of the lens circumference (Grade cortical
cataract-2 [COR-2]) or a posterior subcapsular cataract
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Stage 1<br /><br>Primary endpoint:<br /><br>*Annualized rate of change in TKV based on MRI from baseline to 18 months.<br /><br><br /><br>Stage 2<br /><br>Primary endpoint:<br /><br>*Annualized rate of change in eGFR (CKD-EPI equation) from baseline to 24<br /><br>months.</p><br>
- Secondary Outcome Measures
Name Time Method