A Study of Patients With Chronic Kidney Disease to Assess the Safety of a Single Dose of COR-001 (COR-001-SC1)

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 1

Conditions: Chronic Kidney Diseases

Treatments: Drug: COR-001; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03126318

16-2272

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a single dose of the study drug or placebo administered subcutaneously to patients with moderate-to-severe chronic kidney disease and persistent inflammation.

Full description

This is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a single dose of the study drug or placebo administered subcutaneously to patients with moderate-to-severe chronic kidney disease (CKD) and persistent inflammation (defined as a persistently elevated serum CRP (C-Reactive Protein) level). The primary objective is to evaluate the safety of a single dose of the study drug delivered subcutaneously. Four CKD patients will be randomized to the study drug or placebo within each dosing cohort in a ratio of 3:1. The dosing cohorts are 5 mg, 15 mg, 50 mg, and 100 mg. Each patient will be given 1 dose of the study drug and then be followed for 12 weeks for primary safety, pharmacokinetic and pharmacodynamic assessments. Next, patients will continue to be followed for an additional 20 weeks (32 weeks observation in total) for safety and anti-drug antibody assessments.

Prior to dose escalation (i.e., higher total dose than studied in the preceding cohorts), there will be a formal safety review and the data will have been determined to be acceptable by a Data Safety Monitoring Board (DSMB) which will include at least one nephrologist. The safety review required for dose escalation will include at least 21 days of treatment data from the preceding cohort(s). The DSMB will also meet to review data concerning an SAE (Serious Adverse Event) that is suspected to be study drug related

The investigative team (other than an un-blinded research pharmacist or equivalent) will be blinded to the treatment assignment.

Enrollment: 32 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. CKD stage III or IV
2. Serum CRP > 2 mg/L measured twice during the Screening period at least one week apart
3. Urine protein excretion < 3.5 g/24h estimated by a spot urine protein/creatinine ratio
4. The patient agrees to comply with the contraception and reproduction restrictions of the study - use 2 forms of acceptable contraception

Exclusion criteria

1. Patients with advanced CKD requiring chronic dialysis

2. Hospitalization over the period of 6 weeks prior to randomization

3. Use of systemic immunosuppressive drugs during the Screening Period or anticipated use of such drugs anytime during the study Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary.

4. History of or expected to undergo living related kidney transplant during the study period

5. Currently receiving or planning to receive live or inactivated vaccines

6. Clinical evidence or suspicion of active or smoldering infection (e.g., diabetic foot ulcer) or use of antibiotics during the Screening period

7. History of a positive PPD or prior diagnosis of tuberculosis

8. Evidence of HIV infection or carrier state by serology at Screening

9. Hepatitis B or C by serology (i.e. Hepatitis B Surface Antigen or Hepatitis C antibody positive) at Screening

10. AST or ALT > 2.5x ULN at Screening

11. History of liver cirrhosis or home oxygen use

12. History of gastrointestinal ulceration or active diverticulitis in the 1 year prior to Screening

13. Absolute neutrophil count < 2 x 109/L at Screening

14. Platelet count < 100 x 109/L at Screening

15. Participated in an investigational drug study within 30 days of Screening or Screening is within 5 half-lives of the investigational compound.

16. Known allergy to the study drug or any of its ingredients

17. Breastfeeding or a positive pregnancy test at Screening or Day -1.

18. Any condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would in the opinion of the Investigator increase the risk of the subject's participation in the study.

    This would include but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy, anemia attributable to a primary hematologic disease (e.g., sickle cell anemia), or any unexplained blackouts.

19. Actively treated malignancy (other than non-melanoma skin cancers) during the 1 year prior to Screening. Patients receiving hormonal treatment only during this period only may be enrolled with the approval of the medical monitor.

20. Myocardial infarction during the 3 months prior to Screening or during Screening

21. Severe arthritis, lupus, inflammatory bowel disease, asthma or other disease(s) or medical condition(s) that, in the opinion of the investigator, could interfere with hs-CRP or immune function

22. Use of CYP substrates with a narrow therapeutic index (please see detailed table below).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

COR-001

Active Comparator group

Description:

COR-001 5, 15, 50, or 100 mg dose (depending on dose cohort assigned to patient) given by subcutaneous injection one time only

Treatment:

Drug: COR-001

Placebo

Placebo Comparator group

Description:

Placebo at pH 6.0will be given in a volume to match the volume of COR-001 being given for the dose cohort by subcutaneous injection one time only

Treatment:

Drug: Placebo