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

NCT ID: NCT03126318

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-19
• Study Completion Date: 2019-12-19

Brief Summary

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.

Detailed 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.

Conditions

Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

COR-001

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

Group Type: ACTIVE_COMPARATOR

COR-001

Intervention Type: DRUG

Anti-inflammatory therapy

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sterile water with a final buffer of 25 mM Histidine, 8.5% (w/v) trehalose and 0.05% PS80

Interventions

COR-001

Anti-inflammatory therapy

Intervention Type: DRUG

Placebo

Sterile water with a final buffer of 25 mM Histidine, 8.5% (w/v) trehalose and 0.05% PS80

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Corvidia Therapeutics

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michel Chonchol, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Coloardo Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

References

Nowak KL, Kakkar R, Devalaraja M, Lo L, Park W, Gobburu J, Kling D, Davidson M, Chonchol M. A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKD. Kidney360. 2020 Dec 4;2(2):224-235. doi: 10.34067/KID.0005862020. eCollection 2021 Feb 25.

Reference Type: DERIVED

PMID: 35373026 (View on PubMed)

Other Identifiers

16-2272

Identifier Type: -

Identifier Source: org_study_id