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

Phase 2

Completed

• Conditions: Renal Anemia
• Interventions: Drug: AND017; Drug: Placebo

• Registration Number: NCT05035641
• Lead Sponsor: Kind Pharmaceuticals LLC

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.

Study Timeline

• Study First Submitted: 2021-04-21
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-05
• Study Start: 2021-10-18
• Primary Completion: 2023-07-05
• Study Completion: 2023-07-24
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-02
• Last Update Posted: 2023-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 113

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.

14. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AND017 Dose B	AND017	AND017 will be administrated orally at dose B
Placebo	Placebo	Placebo will be administrated orally
AND017 Dose C	AND017	AND017 will be administrated orally at dose C
AND017 Dose A	AND017	AND017 will be administrated orally at dose A

Primary Outcome Measures

Name	Time	Method
Safety Evaluations	Up to 17 weeks	Incidence of adverse events
Rate of rise in hemoglobin for each of 3 dose levels as compared with placebo from baseline to 5 weeks after TIW oral dosing	Up to 5 weeks after dosing	Calculate the slope of a linear regression for each patient using all hemoglobin data collected during the Fixed-Dose Period

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Hb	Up to 13 weeks after dosing	Change from baseline in Hb
To assess iron utilization parameter during treatment - total iron-binding capacity (TIBC)	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose	To assess TIBC level during treatment
Hb response to treatment during Period 1	Up to 5 weeks after dosing	Cumulative percentage of patients with Hb ≥10.0 g/dL
Percentage of responder patients	Up to 13 weeks after dosing	Responder is defined as a hemoglobin ≥10.0 g/dL and an increase in hemoglobin by ≥1.0 g/dL
Change in hemoglobin levels from baseline to the mean of weeks 10-13	Baseline and at Week 10, 11, 12, 13, and 14	Change in hemoglobin levels from baseline to the mean of weeks 10-13
To assess changes in the levels of PD indicator - 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 EPO
To assess changes in the levels of PD indicator - hepcidin	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 hepcidin
To assess iron utilization parameter during treatment - transferrin level	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose	To assess transferrin level during treatment
To assess iron utilization parameters during treatment - serum iron	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose	To assess serum iron level during treatment
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	Percentage of visits at which patients maintain hemoglobin between 10.0-11.0 g/dL after achieving hemoglobin ≥10.0 g/dL
Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit	Up to 13 weeks after dosing	Percentage of patients who maintain hemoglobin between 10.0-11.0g/dL at each visit
Mean Hb levels at weeks 6-14 including the average of weeks 10-13	Up to 13 weeks after dosing	Mean Hb levels at weeks 6-14 including the average of weeks 10-13
Cumulative incidence of lack of response over the entire treatment period	Up to13 weeks after dosing	Hb level \< 10.0 g/dL and an increase in hemoglobin from baseline of \< 1 g/dL
To assess iron utilization parameter during treatment - transferrin saturation (TSAT)	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose	To assess TSAT level during treatment
To assess iron utilization parameters during treatment - ferritin	Baseline and at Week 3, 6, 9, 12, 14, and 28 days after the last dose	To assess ferritin level during treatment

Trial Locations

Locations (8)

Clinical Site Partners; 🇺🇸 Winter Park, Florida, United States

Amicis Research Center; 🇺🇸 Northridge, California, United States

Metrolina Nephrology Associates; 🇺🇸 Charlotte, North Carolina, United States

Northwest Louisiana Nephrology; 🇺🇸 Shreveport, Louisiana, United States

Elite Research Center; 🇺🇸 Flint, Michigan, United States

Southeast Renal Research Institute; 🇺🇸 Chattanooga, Tennessee, United States

Clinical Advancement Center, PLLC; 🇺🇸 San Antonio, Texas, United States

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China