Study of DISC-0974 to Assess the Safety, Tolerability, PK and PD of DISC-0974 in Participants With CKD and Anemia

Disc Medicine

Status and phase: Enrolling; Phase 1

Conditions: Anemia of Chronic Kidney Disease; Chronic Kidney Diseases

Treatments: Drug: DISC-0974; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05745883

DISC-0974-103

Details and patient eligibility

About

This Phase 1b study of DISC-0974 will assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of DISC-0974 in adult participants with Non-Dialysis Dependent Chronic Kidney Disease and Anemia.

Enrollment: 32 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged ≥18 years of age at the time of signing informed consent.
2. Non-dialysis dependent chronic kidney disease, stages 2-5, defined as eGFR <90 mL/min/1.73m2 using the 2021 CKD-EPI formula
3. Hemoglobin ≤11.0 g/dL
4. Serum ferritin ≥75 μg/L at Screening
5. Transferrin saturation ≤35%
6. Body mass index (BMI) of 18.5 to 45.0 kg/m2, inclusive, at screening
7. Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2× upper limit of normal (ULN) at Screening.
8. Total and direct bilirubin <ULN at Screening.

Exclusion criteria

1. Treatment within 2 days prior to screening with oral iron or iron-containing supplements. Participants may be considered for the study if they undergo a 2-day washout period prior to signing the informed consent form (ICF) and screening for oral iron or iron-containing supplements.
2. Treatment within 30 days prior to screening with one of the following anemia treatments: erythropoietin-stimulating agent or IV iron. Participants may be considered for the study if they undergo a 30-day washout period prior to signing the informed consent form (ICF) and screening for erythropoietin-stimulating agent or IV iron.
3. Acute dialysis or acute kidney injury within 12 weeks prior to screening or expected need to start dialysis within 12 weeks of screening.
4. Hospitalization for a cardiovascular, renal, or cardiorenal condition within 30 days prior to screening.
5. Positive direct antiglobulin test with reactive eluate at screening or active hemolytic anemia.
6. History of hereditary hemochromatosis.
7. History of hemoglobinopathy or intrinsic red blood cell defect associated with anemia.
8. History of total splenectomy.
9. Hematopoietic stem cell or solid organ transplant within the past 10 years.
10. Medical history of anemia from Vitamin B12 or folate deficiency, infection, or bleeding in the 3 months prior to screening
11. Blood transfusion within 3 months of screening
12. Stroke, myocardial infarction, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to Screening
13. If female, pregnant or breastfeeding.
14. Any major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
15. History of malignancy within the last 3 years. The following history/concurrent conditions are allowed: basal or squamous cell carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system). A history of completed treatment (medical or surgical) of Stage 1-2 cancers may be permitted with prior Sponsor agreement.
16. Participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening
17. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug
18. History of anti-drug antibody formation
19. History of inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or have a history of left ventricular ejection fraction <35%
20. Uncontrolled fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement, despite appropriate treatment)
21. Human immunodeficiency virus positive, active Hepatitis B, or active Hepatitis C.
22. Uncontrolled diabetes mellitus or diabetes mellitus requiring initiation of insulin therapy within 3 months of screening
23. Significant medical condition, laboratory abnormality, or psychiatric condition that would prevent the patient from participating in the study.
24. Any condition or concomitant medication that would confound the ability to interpret data from the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Phase 1b Dose Escalation

Experimental group

Description:

Single ascending dose of DISC-0974

Treatment:

Drug: DISC-0974

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo