Clinical trial NCT05035641: A Study of AND017 to Treat Anemia in Non-dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients
Official title: A Pilot Phase II Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging, Safety and Efficacy Study of Oral AND017 to Treat Anemia in Nondialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Anemia
Lead sponsor: Kind Pharmaceuticals LLC
Sponsor class: INDUSTRY
First posted: 2021-09-05
Enrollment: 113
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a pilot phase II study to evaluate the safety and efficacy of AND017 in NDD-CKD patients

Detailed description: This is a pilot phase 2, multicenter, randomized, parallel-group, double-blind, placebo-controlled, dose-ranging, safety and efficacy study of oral AND017 to treat anemia in non-dialysis-dependent chronic kidney disease patients.

Eligibility criteria: Key Inclusion Criteria:

1. Diagnosis of chronic kidney disease, not receiving dialysis, with an eGFR \<60 mL/min/1.73 m2.
2. Baseline Hb level ≥ 7.5 g/dL and \<10.0 g/dL.
3. TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening test
4. Serum folate and vitamin B12 ≥ lower limit of normal at screening test
5. AST and ALT ≤ 3×ULN.
6. Total bilirubin ≤ 1.5×ULN.

Key Exclusion Criteria:

1. Concurrent retinal neovascular lesions requiring treatment including proliferative diabetic retinopathy, exudative age-related macular degeneration, retinal vein occlusion, macular edema, etc.
2. Anemia that is possibly mainly caused by concurrent autoimmune disease with inflammatory symptoms
3. History of gastric/intestinal resection considered to affect the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent symptomatic gastroparesis despite being on treatment.
4. Clinically significant bleeding (eg, requiring transfusion or drop in Hb of ≥ 2g/dL) within 4 weeks of first dose; no bleeding diathesis or risk of bleeding that has not been medically or surgically corrected at least 4 weeks prior to first dose of study drug.
5. Uncontrolled hypertension defined as patients with hypertension having more than one of three diastolic blood pressure values \>95 mmHg and each test at least 5 min apart during the screening assessment.
6. Concurrent congestive heart failure (New York Heart Association \[NYHA\] Class III or higher).
7. History of stroke, transient ischemic attack, myocardial infarction, thromboembolic event, pulmonary embolism, or lung infarction within 24 weeks before the screening assessment.
8. Concurrent anemia due to another cause other than renal anemia
9. Known hemosiderosis, hemochromatosis or hyper-coagulable condition
10. Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks before randomization.
11. Having received treatment with erythropoiesis stimulating agents, androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks before the first dose.
12. Total bilirubin \>1.5xULN, or AST\>3xULN, or ALT\>3xULN, or ALP\>3xULN, or previous or concurrent serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.) thought to be caused by ESAs.
13. Patients with a history of significant liver disease or active liver disease. Investigators should discuss this with the Medical Monitor for cases where there is doubt about whether to exclude or not.

13. Patients that have major surgery planned during the study period. 14. Having undergone blood transfusion and/or a surgical procedure within 8 weeks before the screening assessment.

15. Having undergone a kidney transplantation. 16. History of a seizure disorder or any occurrence of seizures in the past

Primary outcomes:
measure: Safety Evaluations
timeFrame: Up to 17 weeks
measure: Rate of rise in hemoglobin for each of 3 dose levels as compared with placebo from baseline to 5 weeks after TIW oral dosing
timeFrame: Up to 5 weeks after dosing
Secondary outcomes:
measure: Hb response to treatment during Period 1
timeFrame: Up to 5 weeks after dosing
measure: Percentage of responder patients
timeFrame: Up to 13 weeks after dosing
measure: Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin ≥10.0 g/dL
timeFrame: Up to 13 weeks after dosing
measure: Change from baseline in Hb
timeFrame: Up to 13 weeks after dosing
measure: Change in hemoglobin levels from baseline to the mean of weeks 10-13
timeFrame: Baseline and at Week 10, 11, 12, 13, and 14
measure: Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit
timeFrame: Up to 13 weeks after dosing
measure: Mean Hb levels at weeks 6-14 including the average of weeks 10-13
timeFrame: Up to 13 weeks after dosing
measure: Cumulative incidence of lack of response over the entire treatment period
timeFrame: Up to13 weeks after dosing
measure: To assess changes in the levels of PD indicator - EPO
timeFrame: Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose
measure: To assess changes in the levels of PD indicator - hepcidin
timeFrame: Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose
measure: To assess iron utilization parameter during treatment - transferrin level
timeFrame: Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
measure: To assess iron utilization parameter during treatment - total iron-binding capacity (TIBC)
timeFrame: Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
measure: To assess iron utilization parameter during treatment - transferrin saturation (TSAT)
timeFrame: Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
measure: To assess iron utilization parameters during treatment - ferritin
timeFrame: Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
measure: To assess iron utilization parameters during treatment - serum iron
timeFrame: Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Amicis Research Center
state: California
city: Winter Park
country: United States
facility: Clinical Site Partners
state: Florida
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Flint
country: United States
facility: Elite Research Center
state: Michigan
city: Charlotte
country: United States
facility: Metrolina Nephrology Associates
state: North Carolina
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Kind Pharmaceuticals LLC
name: Yusha Zhu, MD PhD
role: STUDY_DIRECTOR
References: