Clinical trial NCT04913272: Clinical Trial To Evaluate Safety And Efficacy Of KT-301 (Formerly US-APR2020) In Subjects With Chronic Kidney Disease Stage IV
Official title: A Double-Blind, Randomized, Placebo-Controlled Phase 2 Clinical Trial To Evaluate Safety And Efficacy Of KT-301 (Formerly US-APR2020) In Subjects With Chronic Kidney Disease Stage IV
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Chronic Kidney Disease stage4
Lead sponsor: Kibow Pharma
Sponsor class: INDUSTRY
First posted: 2021-06-04
Enrollment: 630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Phase 2 double-blind, randomized, placebo-controlled, multicenter clinical trial to evaluate the safety and efficacy of KT-301 (formerly US-APR2020) in patients with CKD Stage IV.

Following Screening and Enrollment, patients will be Randomized to either Group KT-301 or Placebo. In Group KT-301, the drug KT-301 will be administered orally at 2 capsules per day (one capsule in the morning and one capsule in the evening, after meals, for a total daily dose of 90 Billion CFUs) for six months. Subjects will be followed for 6 months. Patients in Placebo Group will be administered Placebo tablets in similar routine.
Primary purpose: TREATMENT

Brief summary: The aim of this Phase 2 study is to evaluate the safety and efficacy of the live biotherapeutic product, KT-301 (formerly US-APR2020), in the management of patients with CKD Stage IV.

Detailed description: Kidney diseases are a global public health problem that affects over 200 million people worldwide. It is estimated that about 30 million adults in the United States have Chronic Kidney Disease (CKD) and most are undiagnosed. In addition, CKD represents the ninth leading cause of death in the United States. Kidney diseases also represent great socio-economical cost worldwide. In the United States, treating Medicare beneficiaries with CKD costed over $79 billion, and treating people with End Stage Kidney Disease (ESKD) costed an additional $35 billion in 2016. To date, there is no cure for CKD.

The most important CKD risk factors in adults include diabetes and high blood pressure. Other risk factors include heart disease, obesity, a family history of CKD, past damage to the kidneys, and old age. Having CKD increases the chances of also having heart disease and stroke.

CKD is a condition characterized by a gradual loss of kidney function over time. Depending on the kidney function measured with glomerular filtration rate (GFR) CKD can be classified into several stages (I, II, III, IV and V). CKD Stage V, also known as End Stage Kidney Disease (ESKD), is a very advanced stage of kidney disease where the kidneys have lost nearly all ability to do their job effectively, and eventually dialysis or a kidney transplant is needed to live. Treatment may slow the decline in kidney function and failure. However, not everyone with CKD develops ESKD, and in some cases ESKD develops even with treatment.

CKD is accompanied by altered pathogenic gut bacteria, inflammation, and accumulation of uremic toxins in the blood. These blood uremic toxins can diffuse passively into the bowel. Scientific research has shown that probiotic bacteria could metabolize various uremic toxins such as urea, uric acid, and creatinine. In addition, by supplementing the gut microbiome with probiotic bacteria, it is possible to metabolize the nitrogenous waste products and other toxins which diffuse into the gut, and thus lower levels of inflammation and blood uremic toxins.

KT-301 (formerly US-APR2020) is a live biotherapeutic (LBT) intended to restore the gut microbiome to improve the removal of uremic toxins in the bowel in CKD patients. The aim of this Phase 2 study is to evaluate the safety and efficacy of the KT-301 in the management of patients with CKD Stage IV.

Eligibility criteria: Inclusion Criteria:

* Adults between the ages of 18-80 years
* CKD Stage IV (eGFR = 15-29 mL/min) with declining kidney function for a period \> 6 months
* Serum Creatinine \> 2.0 mg/dL
* Adherence to low protein diet (LPD) of 0.6-0.8 g/kg/day based on subject response and on advisory

Exclusion Criteria:

* Those on probiotic supplements in the past 3 months
* Pregnancy, breast feeding or females of child-bearing potential who are unwilling to use a reliable form of contraception.
* Immunosuppressant medications therapy specific to immune mediated renal diseases
* HIV/AIDs
* Underweight (BMI ≤ 18.5)
* Subject with an infection that requires oral antibiotic administration at the time of randomization or close to that visit.
* Those with gastrointestinal disease (irritable bowel syndrome or anal fissures or anal fistulas or perianal abscesses or perianal infections or diverticular diseases or colitis or colon polyps) at the time of screening and randomization, or within 6 months prior to the randomization visit (Visit 2)
* Those with internal prosthesis including orthopedics, neurosurgery, heart valves, vascular stents ˂ 2 years post -surgery procedure. Those with Prosthesis \> 2 years should not be excluded.
* Those with biological/tissue grafts or prosthesis or implant
* Those on anticoagulant medicines, including Vit K antagonists (e.g., warfarin, coumadin) or the new class of oral anti-coagulants approved by FDA in the last 10 years
* Those on peritoneal dialysis
* Those with acute kidney injury
* Those with mental conditions or medically debilitating disease/disorder other than CKD, which, in the judgment of the investigator, would interfere with or serve as a contraindication to adherence to the study protocol or affect the ability to give informed consent or affect overall prognosis of the patient.

Primary outcomes:
measure: Evaluate incidences of Treatment-Emergent Adverse Events following KT-301 (formerly US-APR2020) administration in patients with Chronic Kidney disease (CKD) Stage IV as a measure of safety.
timeFrame: six months
measure: Evaluate the change of eGFR as per NKF-USFDA guidelines following KT-301 (formerly US-APR2020) administration in patients with Chronic Kidney disease (CKD) Stage IV as a measure of clinical efficacy.
timeFrame: six months
Secondary outcomes:
measure: Evaluate changes in basic blood uremic metabolic markers
timeFrame: six months
measure: Evaluate changes in complete blood count and hematology parameters
timeFrame: six months
measure: Evaluate changes in C-Reactive Protein (CRP) levels
timeFrame: six months
measure: Evaluate change in quality of life (QOL)- SF36 QOL questionnaire
timeFrame: six months
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Jadedstone Clinical Research
state: Maryland
city: Saginaw
country: United States
facility: Kidney Michigan
state: Michigan
city: Orangeburg
country: United States
facility: South Carolina Clinical Research
state: South Carolina
city: Houston
country: United States
facility: Almeda Medical Clinic
state: Texas
city: Woodbridge
country: United States
facility: Mendez Center for Clinical Research
state: Virginia
Study officials:
References: