A Study of AND017 to Treat Anemia in Non-dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients

Renal Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05035641
• Other study ID #: AND017-MN-201
• Status: Completed
• Phase: Phase 2
• Start date: October 18, 2021
• Est. completion date: July 24, 2023

Study information

• Verified date: October 2023
• Source: Kind Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: July 24, 2023
• Est. primary completion date: July 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Kidney Diseases
• Renal Anemia
• Renal Insufficiency, Chronic

Intervention

Drug:
• AND017
Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2
• Placebo
Orally, 3 times per week

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing
United States	Metrolina Nephrology Associates	Charlotte	North Carolina
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	Elite Research Center	Flint	Michigan
United States	Amicis Research Center	Northridge	California
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	Northwest Louisiana Nephrology	Shreveport	Louisiana
United States	Clinical Site Partners	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kind Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Evaluations	Incidence of adverse events	Up to 17 weeks
Primary	Rate of rise in hemoglobin for each of 3 dose levels as compared with placebo from baseline to 5 weeks after TIW oral dosing	Calculate the slope of a linear regression for each patient using all hemoglobin data collected during the Fixed-Dose Period	Up to 5 weeks after dosing
Secondary	Hb response to treatment during Period 1	Cumulative percentage of patients with Hb =10.0 g/dL	Up to 5 weeks after dosing
Secondary	Percentage of responder patients	Responder is defined as a hemoglobin =10.0 g/dL and an increase in hemoglobin by =1.0 g/dL	Up to 13 weeks after dosing
Secondary	Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin =10.0 g/dL	Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin =10.0 g/dL	Up to 13 weeks after dosing
Secondary	Change from baseline in Hb	Change from baseline in Hb	Up to 13 weeks after dosing
Secondary	Change in hemoglobin levels from baseline to the mean of weeks 10-13	Change in hemoglobin levels from baseline to the mean of weeks 10-13	Baseline and at Week 10, 11, 12, 13, and 14
Secondary	Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit	Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit	Up to 13 weeks after dosing
Secondary	Mean Hb levels at weeks 6-14 including the average of weeks 10-13	Mean Hb levels at weeks 6-14 including the average of weeks 10-13	Up to 13 weeks after dosing
Secondary	Cumulative incidence of lack of response over the entire treatment period	Hb level < 10.0 g/dL and an increase in hemoglobin from baseline of < 1 g/dL	Up to13 weeks after dosing
Secondary	To assess changes in the levels of PD indicator - EPO	To assess changes in the levels of EPO	Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose
Secondary	To assess changes in the levels of PD indicator - hepcidin	To assess changes in the levels of hepcidin	Baseline and at Week 2, 4, 6, 8, 10, 12, 14, and 28 days after the last dose
Secondary	To assess iron utilization parameter during treatment - transferrin level	To assess transferrin level during treatment	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
Secondary	To assess iron utilization parameter during treatment - total iron-binding capacity (TIBC)	To assess TIBC level during treatment	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
Secondary	To assess iron utilization parameter during treatment - transferrin saturation (TSAT)	To assess TSAT level during treatment	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
Secondary	To assess iron utilization parameters during treatment - ferritin	To assess ferritin level during treatment	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose
Secondary	To assess iron utilization parameters during treatment - serum iron	To assess serum iron level during treatment	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose