A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis

Phase 2

Completed

• Conditions: Renal Anemia
• Interventions: Drug: AND017 capsules TIW; Drug: AND017 capsules QW; Drug: epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars

• Registration Number: NCT05265325
• Lead Sponsor: Kind Pharmaceuticals LLC

Brief Summary

This is a phase II study to evaluate the safety and efficacy of AND017 in renal anemia patients on dialysis

Detailed Description

This is a Phase II study to assess the safety and efficacy of AND017 in patients with CKD who are anemic and on dialysis.

Study Timeline

• Study First Submitted: 2022-02-22
• Study First Submitted QC: 2022-02-22
• Study First Posted: 2022-03-03
• Study Start: 2023-05-03
• Primary Completion: 2024-02-29
• Study Completion: 2024-04-25
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

1. Body weight from 45 to 140 kg inclusive
2. Receiving stable HD (including combination methods such as hemodiafiltration or hemofiltration), HHD, or PD for ESKD for a minimum of 16 weeks prior to randomization and determined by the Investigator to be compliant with dialysis treatment prescription.
3. Patient must have been on IV or SC of an approved ESA under the prescription for at least 6 weeks, and ≤25% change in dose between the two most recent doses, prior to randomization.
4. The mean of two hemoglobin values during screening (at least 7 days apart) must be 9.0-11.0 g/dL with a difference of ≤1.3 g/dL between the two values
5. TSAT ≥ 20% or ferritin ≥ 100 ng/mL at screening
6. Folate ≥ 3.0 ng/mL and vitamin B12 ≥ lower limit of normal (LLN) at screening
7. AST and ALT < 3×ULN at screening.
8. No evidence of other causes of anemia caused by a pathologic process in the hematopoietic system, including intra- or extravascular hemolysis, or myelodysplasia.

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 determined by the Investigator to be caused by concurrent autoimmune disease with inflammatory symptoms (such as systemic erythematosus, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, Sjögren's syndrome, celiac disease, etc.).
3. History of gastric/intestinal resection considered influential on the absorption of drugs in the gastrointestinal tract (excluding resection of gastric or colon polyps) or concurrent symptomatic gastroparesis despite on treatment.
4. Clinically significant bleeding (eg, requiring transfusion or drop in Hb of ≥ 2 g/dL) within 4 weeks of first dose; 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 (TIA), myocardial infarction, thromboembolic event (deep vein thrombosis, DVT), pulmonary embolism, or lung infarction within 24 weeks before the screening assessment.
8. Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody at the screening assessment, or positive for human immunodeficiency virus in a past test.
9. Not complying with COVID-19 prevention and control requirements per local policy.
10. Concurrent primary form of anemia other than renal anemia (hemolytic anemia, thalassemia, sickle cell anemia, history of pure red cell aplasia, history of myelodysplastic syndrome or multiple myeloma, iron deficiency, etc.). Any question of the primary cause of anemia should be discussed with the Medical Monitor before the patient signs informed consent.
11. Known hemosiderosis, hemochromatosis or hyper-coagulable condition
12. Known to be hypersensitive or intolerant to ESA.
13. Having received treatment with androgenic anabolic steroids, testosterone enanthate, or mepitiostane within 5 weeks prior to the first dose.
14. Any treatment with a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) within 5 weeks prior to the first dose.
15. TBIL>1.5 ULN, or AST>3 ULN, or ALT>3 ULN, or ALP>3 ULN, or previous or concurrent serious liver disease (acute or active chronic hepatitis, cirrhosis, etc.) thought to be caused by any other HIF-PHI.
16. Previous or current malignant tumor (patients with no recurrence for at least 5 years are eligible. Exemption: basal cell and squamous cell carcinoma not under active stage).
17. Patients with a history of significant liver disease or active liver disease.
18. Patients that have major surgery planned during the study period.
19. Patients that have undergone blood transfusion or with evidence of major blood loss within 8 weeks before the screening assessment. Investigators should discuss this with the Medical Monitor for cases where there is doubt about whether to exclude or not.
20. Patients unable to discontinue IV iron during the screening period.
21. Patients with an organ transplant on immunosuppression, or with a scheduled kidney or any other organ transplant within the duration of the study, or without kidney.
22. Serum albumin < 2.5 g/dL at screening.
23. Patients with other chronic medical condition that may limit life expectancy in the opinion of the Investigator.
24. 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 Regimen A	AND017 capsules TIW	AND017 will be administrated orally at dose A three times a week
AND017 Dose Regimen B	AND017 capsules QW	AND017 will be administrated orally at dose B once a week
Erythropoietin stimulating agent	epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars	Investigator will select an erythropoietin stimulating agent, such as epoetin alfa, darbepoetin alfa, Mircera®, or their biosimilars, for the patient under this arm with starting doses and dose adjustment rules according to the epoetin alfa USPI or SmPC.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 20 weeks	Incidence of adverse events
Mean change from baseline in Hb at Week 6	Up to 5 weeks after dosing	Mean change from baseline in Hb at Week 6

Secondary Outcome Measures

Name	Time	Method
Proportion of responders, during the entire study period.	up to Week 20	Responders are defined as patients whose Hb achieved ≥ 10.0 g/dL and an increase ≥ 1.0 g/dL from baseline
Mean proportion of visits at which patients maintain Hb within the target range from baseline during the fixed-dose period and titration period	up to Week 20	Target range is defined as 10.0-11.0 g/dL inclusive and an increase ≥ 1.0 g/dL.
Proportion of patients with a mean Hb between 10.0-11.0 g/dL inclusive during Week 14-20	at Week 14, 15, 16, 17, 18, 19, and 20	Proportion of patients with a mean Hb between 10.0-11.0 g/dL inclusive during Week 14-20
Change in Hb from baseline to the mean Hb levels over Week 14-20	Baseline and at Week 14, 15, 16, 17, 18, 19, and 20	Change in Hb from baseline to the mean Hb levels over Week 14-20
Mean Hb levels and mean change from baseline in Hb level at each visit	up to Week 20	Mean Hb levels and mean change from baseline in Hb level at each visit
Cumulative response rate over the entire study period	up to Week 20	Response is defined as Hb \< 10.0 g/dL or an increase in hemoglobin of \<1 g/dL from baseline

Trial Locations

Locations (25)

North America Research Institute; 🇺🇸 Riverside, California, United States

US Renal Care - Pine Bluff; 🇺🇸 Pine Bluff, Arkansas, United States

The Affiliated Zhongshan Hospital of Dalian University; 🇨🇳 Dalian, Liaoning, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, Fujian, China

Zhongshan Hospital affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, Sichuan, China

Rocky Mountain Kidney Care; 🇺🇸 Lone Tree, Colorado, United States

High Desert Nephrology Associates; 🇺🇸 Gallup, New Mexico, United States

Nephrology and Hypertension Specialists; 🇺🇸 Dalton, Georgia, United States

South Texas Renal Care Group - San Saba; 🇺🇸 San Antonio, Texas, United States

Nephrology Consultants of Northwest Ohio - Toledo; 🇺🇸 Toledo, Ohio, United States

South Texas Renal Care Group; 🇺🇸 San Antonio, Texas, United States

Nephrology Associates of Western New York; 🇺🇸 Cheektowaga, New York, United States

The Second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

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

Xiamen Fifth Hospital; 🇨🇳 Xiamen, Fujian, China

Renmin Hospital of Wuhan University; 🇨🇳 Wuhan, Hunan, China

Xiamen Branch, Zhongshan hospital affilicated to Fudan University; 🇨🇳 Xiamen, Fujian, China

The First Affiliated Hospital of Henan University of Science and Technology; 🇨🇳 Luoyang, Henan, China

Second Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

The First People's Hospital of Changzhou; 🇨🇳 Changzhou, Jiangsu, China

Second Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Jinshan Hospital Affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China

First Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

Zigong First People's Hospital; 🇨🇳 Zigong, Sichuan, China