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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Chronic Kidney Diseases, Anemia of Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: DISC-0974
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Aged ≥18 years of age at the time of signing informed consent. Non-dialysis dependent chronic kidney disease, stages 2-5, defined as eGFR <90 mL/min/1.73m2 using the 2021 CKD-EPI formula Women: Hemoglobin <10.5 g/dL; Men: Hemoglobin <11.0 g/dL Serum ferritin ≥100 μg/L at Screening Transferrin saturation ≤35% Body mass index (BMI) of 18.5 to 45.0 kg/m2, inclusive, at screening Aspartate aminotransferase (AST) and alanine transaminase (ALT) <2× upper limit of normal (ULN) at Screening. Total and direct bilirubin <ULN at Screening. Exclusion Criteria: 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. 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. Acute dialysis or acute kidney injury within 12 weeks prior to screening or expected need to start dialysis within 12 weeks of screening. Hospitalization for a cardiovascular, renal, or cardiorenal condition within 30 days prior to screening. Positive direct antiglobulin test with reactive eluate at screening or active hemolytic anemia. History of hereditary hemochromatosis. History of hemoglobinopathy or intrinsic red blood cell defect associated with anemia. History of total splenectomy. Hematopoietic stem cell or solid organ transplant within the past 10 years. Medical history of anemia from Vitamin B12 or folate deficiency, infection, or bleeding in the 3 months prior to screening Blood transfusion within 3 months of screening Stroke, myocardial infarction, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to Screening If female, pregnant or breastfeeding. Any major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery. 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. Participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug History of anti-drug antibody formation 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% Uncontrolled fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement, despite appropriate treatment) Human immunodeficiency virus positive, active Hepatitis B, or active Hepatitis C. Uncontrolled diabetes mellitus or diabetes mellitus requiring initiation of insulin therapy within 3 months of screening Significant medical condition, laboratory abnormality, or psychiatric condition that would prevent the patient from participating in the study. Any condition or concomitant medication that would confound the ability to interpret data from the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b Dose Escalation<br>Single ascending dose of DISC-0974 | Drug: DISC-0974<br>* DISC-0974 is administered subcutaneously<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo is administered subcutaneously<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events |  | up to 8 weeks | 
| Incidence of clinically abnormal vital signs |  | up to 8 weeks | 
| Incidence of abnormal laboratory test results |  | up to 8 weeks | 
| Incidence of clinically abnormal physical exam |  | up to 8 weeks | 
| Incidence of clinically abnormal electrocardiograms |  | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in concentration of iron laboratory parameter |  | up to 8 weeks | 
| Change from baseline in concentration of hematologic laboratory parameters |  | up to 8 weeks | 
| Cmax-Maximum drug concentration measured in plasma |  | up to 8 weeks | 
| Tmax-Time of maximum drug concentration |  | up to 8 weeks | 
| AUC-Area under the drug concentration time curve |  | up to 8 weeks | 
| T½ - Elimination half life of the drug |  | up to 8 weeks | 
| CL/F-Apparent drug clearance |  | up to 8 weeks | 
| Vd/F-Apparent volume of distribution of the drug |  | up to 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Kidney Disease, Anemia