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

Chronic Kidney Diseases Clinical Trial

Official title:

A Phase 1b Multicenter, Randomized, Double-Blind, Placebo-Controlled Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of DISC-0974 in Participants With Non-Dialysis Dependent Chronic Kidney Disease and Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05745883
• Other study ID #: DISC-0974-103
• Status: Recruiting
• Phase: Phase 1
• Start date: April 4, 2023
• Est. completion date: May 2025

Study information

• Verified date: March 2024
• Source: Disc Medicine, Inc
• Contact: Disc Medicine Clinical Trials
• Phone: (617) 674 9274
• Email: clinicaltrials[@]discmedicine.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: May 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• DISC-0974
DISC-0974 is administered subcutaneously
• Placebo
Placebo is administered subcutaneously

Locations

Country	Name	City	State
United States	Washington Nephrology Associates, LLP	Alexandria	Virginia
United States	Centricity Research	Columbus	Ohio
United States	Nephrology and Hypertension Specialists, PC-Dalton	Dalton	Georgia
United States	Accel Research	DeLand	Florida
United States	Rocky Mountain Kidney Care - Lone Tree	Lone Tree	Colorado
United States	Total Research Group	Miami	Florida
United States	Boise Kidney & Hypertension PLLC	Nampa	Idaho
United States	Center for Advanced Kidney Research PLC	Saint Clair Shores	Michigan
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	Endeavor Clinical Trials	San Antonio	Texas
United States	Flourish Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Disc Medicine, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events		up to 8 weeks
Primary	Incidence of clinically abnormal vital signs		up to 8 weeks
Primary	Incidence of abnormal laboratory test results		up to 8 weeks
Primary	Incidence of clinically abnormal physical exam		up to 8 weeks
Primary	Incidence of clinically abnormal electrocardiograms		up to 8 weeks
Secondary	Change from baseline in concentration of iron laboratory parameter		up to 8 weeks
Secondary	Change from baseline in concentration of hematologic laboratory parameters		up to 8 weeks
Secondary	Cmax-Maximum drug concentration measured in plasma		up to 8 weeks
Secondary	Tmax-Time of maximum drug concentration		up to 8 weeks
Secondary	AUC-Area under the drug concentration time curve		up to 8 weeks
Secondary	T½ - Elimination half life of the drug		up to 8 weeks
Secondary	CL/F-Apparent drug clearance		up to 8 weeks
Secondary	Vd/F-Apparent volume of distribution of the drug		up to 8 weeks