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

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

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

Study Overview

• Status: Completed
• Conditions: Renal Anemia
• Intervention / Treatment: Drug: AND017; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
• United States
  • California
    • Northridge, California, United States, 91324
      • Amicis Research Center
  • Florida
    • Winter Park, Florida, United States, 32789
      • Clinical Site Partners
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology
  • Michigan
    • Flint, Michigan, United States, 48532
      • Elite Research Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Metrolina Nephrology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Southeast Renal Research Institute
  • Texas
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AND017 Dose A; AND017 will be administrated orally at dose A	Drug: AND017; Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2
Experimental: AND017 Dose B; AND017 will be administrated orally at dose B	Drug: AND017; Orally, 3 times per week in Period 1 and randomize to TIW or QW group at the same dose in Period 2
Experimental: AND017 Dose C; AND017 will be administrated orally at dose C	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 Comparator: Placebo; Placebo will be administrated orally	Drug: Placebo; Orally, 3 times per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Evaluations	Incidence of adverse events	Up to 17 weeks
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb response to treatment during Period 1	Cumulative percentage of patients with Hb ≥10.0 g/dL	Up to 5 weeks after dosing
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
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
Change from baseline in Hb	Change from baseline in Hb	Up to 13 weeks after dosing
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Kind Pharmaceuticals LLC
• Investigators: Study Director: Yusha Zhu, MD PhD, Kind Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Actual): July 5, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Anemia
• Other Study ID Numbers: AND017-MN-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No