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A Phase 3, Multicenter, Multi-country, Open-label, Randomized, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Desidustat Versus Darbepoetin for the Treatment of Anemia in Patients with Chronic Kidney Disease (CKD) who are not on Dialysis.

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SLCTR Registration Number

SLCTR/2019/032


Date of Registration

25 Sep 2019

The date of last modification

Sep 25, 2019



Application Summary


Scientific Title of Trial

A Phase 3, Multicenter, Multi-country, Open-label, Randomized, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Desidustat Versus Darbepoetin for the Treatment of Anemia in Patients with Chronic Kidney Disease (CKD) who are not on Dialysis.


Public Title of Trial

A Randomized, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Desidustat Versus Darbepoetin for the Treatment of Anemia in Patients with Chronic Kidney Disease (CKD) who are not on Dialysis


Disease or Health Condition(s) Studied

Anemia in patients with chronic kidney disease (CKD) who are not on dialysis.


Scientific Acronym

DESI.18.001


Public Acronym


Brief title

Desidustat in the treatment of anemia in CKD


Universal Trial Number

UNT- U1111-1240-5253


Any other number(s) assigned to the trial and issuing authority

ERC ref P/120/06/2019


Trial Details


What is the research question being addressed?

What is the safety and efficacy of desidustat over darbepoetin injection on the haemoglobin levels in anaemic patients with CKD who are not on dialysis?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Masking not used


Control

Active


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 3


Intervention(s) planned

Study Sites • Colombo North Teaching Hospital • National Hospital of Sri-Lanka Subjects will be randomly assigned to receive Desidustat 100 mg Tablet or Darbepoetin Injection in a 1:1 ratio. The randomization schedule will be generated Using SAS® software (Version: 9.4 or higher; SAS Institute Inc., USA). The study will be conducted over a period of up to 30 weeks. Subjects will be evaluated at study sites for 10 scheduled visits: at screening visit (Visit 1: Week -4); randomization visit (Visit 2: Week 0); (Visit 3: Week 2); Visit 4 (Week 4); Visit 5 (Week 6); Visit 6 (Week 8); Visit 7 (Week 12); Visit 8 (Week 16); Visit 9 (Week 20) and end-of-treatment (EOT) (Visit 10: Week 24). Desidustat 100 mg tablet will be orally administered thrice in a week in anemic patients with CKD who are not on dialysis for a period of 24 weeks. Darbepoetin Alfa (Cresp®) dose and dose regimen: Initial dose will be 0.75 mcg/kg. Dose regimen throughout the study will be every 2 weeks till target Hb is achieved and stabilized.


Inclusion criteria

  1. Current clinical diagnosis of anemia due to CKD with baseline hemoglobin concentrations between 7.0-10.0 g/dL (both inclusive) before the enrollment.
  2. Ability to understand and give informed consent for participation.
  3. Male or female patients diagnosed with CKD (stage III to V, not receiving dialysis) defined by estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
  4. Male or female, 18 to 80 years of age.
  5. Body weight > 40 kg.
  6. Subjects not on dialysis and not expected to start dialysis during the study period.
  7. Patients must not be treated with erythropoiesis-stimulating agent (ESA) therapy within 6 weeks prior to enrollment.
  8. Estimated GFR >10 mL/min/1.73 m2.
  9. Serum ferritin >100 ng/mL and/or TSAT >20%.
  10. No iron, folate or Vitamin B12 deficiency.
  11. Females of childbearing potential, must agree to use one of the approved contraception methods, from screening until completion of the follow-up visit.

Exclusion criteria

  1. Prior chronic hemodialysis or chronic peritoneal dialysis treatment.

  2. Intravenous iron within 14 days prior to enrollment.

  3. Prior exposure of rhEPO analogues less than 04 weeks.

  4. Red blood cell transfusion within 8 weeks prior to enrollment.

  5. History of previous or concurrent cancer.

  6. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection.

  7. Active infection prior to enrollment.

  8. History of renal transplant.

  9. Major surgery within 90 days of the first day of study drug dosing, and minor surgery within 30 days of the first day of study drug dosing.

  10. Unable to swallow tablets or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; mal-absorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.

  11. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia.

  12. Presence or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal [GI] bleeding or constitutional disorders) that may increase risk of life-threatening bleeding.

  13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

  14. History of severe allergic or hypersensitivity to investigational products and its excipients.

  15. Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists or other medications within 28 days of the first dose of study drug that in the investigator’s opinion, could compromise patient safety.

  16. Pregnant and breastfeeding women.

  17. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.

  18. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation.

  19. Presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) which, in the Investigator's opinion, could compromise the patient's safety.

  20. History of significant alcoholism or drug abuse within the past 1 year. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).

  21. History of difficulty with donating blood.

  22. History or presence of any clinically significant ECG abnormalities during screening.

  23. Participants who have participated in any drug research study other than the present trial within past 3 months.

  24. Participants who have donated one unit (350 ml) of blood in the past 3 months or history of whole blood transfusion in last 120 days prior to enrollment.

  25. History of chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease, Systemic Lupus Erythematosus [SLE]).

  26. In case of DM patients, glycosylated haemoglobin (HbA1c) >9 %.

  27. In case of hypertensive patients, systolic and diastolic BP is > 160 and 100 mm of Hg respectively or uncontrolled blood pressure.

  28. Female volunteers with following criteria will not be eligible: • History of pregnancy or lactation in the past 3 months. • Fertile female volunteers not protected against pregnancy by adequate long-term anti-fertility measures • History of less than 1 year of menopause and not using adequate long-term antifertility measures • Oral hormone replacement therapy • Positive serum -hCG level at the screening visit

  29. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the NYHA (New York Heart Association) classification.

  30. History of myocardial infarction in the past 6 months.

  31. Abnormal baseline laboratory investigations as follows: • WBC count <3 x 103 /uL • Platelets count <100 x 103 /uL • Bilirubin >2.0 mg/dL • ALT and/or AST >2.5 times of the ULN



Primary outcome(s)

1.

Mean change in haemoglobin

[

(Duration: Week 24)

]

Secondary outcome(s)

1.
  1. Hb responders (Defined as achievement of target level of 10-12 g/dL and post-treatment increase of 1 g/dL or more in Hb by Week 24)

  2. Time to achieve target range Hb level (Defined as Hb level of 10-12 g/dL)

  3. Percentage of time spent in target Hb range

  4. Serum hepcidin level

  5. Serum Potassium (K+)

  6. Quality of life by SF-36 (Short Form (36) Health Survey)

  7. Need for rescue therapy during study treatment

  8. Vascular endothelial growth factor (VEGF) 9 levels

9.Lipid profile and lipoproteins

[

24 Week

]

Target number/sample size

70 randomized subjects from Sri Lanka. (35 patients in each arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2019-09-27


Anticipated end date

2019-12-31


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Cadila Healthcare Ltd. Zydus Tower Satellite Cross Road Ahmedabad 380015 Gujarat, India Tel. No. : +91 79 26868100 Fax No.:+91 79 2686 2363 E-mail: clinical@zyduscadila.com


Regulatory approvals

Approved by National Medicines Regulatory Authority, on 21-Aug-2019 under the reference number NMRA/CTEC/CTM/017/2019



State of Ethics Review Approval


Status

Approved


Date of Approval

2019-08-13


Approval number

P/120/06/2019


Details of Ethics Review Committee

Name: University of Kelaniya
Institutional Address:Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Telephone:011-2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr.A.L.M Nazar
Consultant Nephrologist
National Hospital of Sri-Lanka Colombo 10

0777287400

latiffnazar@hotmail.com

Contact Person for Public Queries

Dr.A.L.M Nazar
Consultant Nephrologist
National Hospital of Sri-Lanka Colombo 10

0777287400

latiffnazar@hotmail.com


Primary study sponsor/organization

Cadila Healthcare Ltd.

Zydus Tower Satellite Cross Road Ahmedabad 380015 Gujarat, India
+91 79 26868100
+91 79 2686 2363
clinical@zyduscadila.com

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description

Details will be submitted through Clinical Study Report as per the local regulatory requirement


Study protocol available

Yes


Protocol version and date

version 1.0, 19 Dec 2018


Protocol URL

N/A

Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results