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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04155125




Registration number
NCT04155125
Ethics application status
Date submitted
29/10/2019
Date registered
7/11/2019
Date last updated
20/11/2020

Titles & IDs
Public title
A Study of Efepoetin Alfa in Treating Anaemia Associated With Chronic Kidney Diseases Patient
Scientific title
Open-Label Randomised Controlled Trial of Efepoetin Alfa for Treatment of Anaemia Associated With Chronic Kidney Disease Patients Not on Dialysis (ND-CKD). A Non- Inferiority Trial Compared to Methoxy Polyethylene Glycol-Epoetin Beta (MIRCERA)
Secondary ID [1] 0 0
GXE4KGBio-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaemia Associated With Chronic Kidney Disease 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - efepoetin alfa
Treatment: Drugs - Mircera

Experimental: efepoetin alfa - Route of administration: Subcutaneous Injection.
The administration interval and initial dosage for subjects who are randomly assigned to subcutaneous efepoetin alfa will be starting from 4 µg/kg BW once per 2 weeks, then titrated based on Hb level during study period.

Placebo Comparator: Mircera - Route of administration: Subcutaneous Injection.
The starting dosage of Mircera arm will be 0.6 µg/kg BW per 2 weeks based on prior data in similar study populations with subsequent titration to achieve targeted Hb range. During the correction treatment period, the dosage of study drug will be adjusted to achieve a Hb level range within 10 - 12 g/dL and an increase =1.0 g/dL versus the individual patient's baseline Hb level. During the extension period, Hb levels should be maintained between 10 and 12 g/dL.


Treatment: Drugs: efepoetin alfa
The administration interval and initial dosage for subjects who are randomly assigned to subcutaneous efepoetin alfa will be starting from 4 µg/kg BW once per 2 weeks, then titrated based on Hb level during study period.

Treatment: Drugs: Mircera
The starting dosage of Mircera arm will be 0.6 µg/kg BW per 2 weeks based on prior data in similar study populations with subsequent titration to achieve targeted Hb range. During the correction treatment period, the dosage of study drug will be adjusted to achieve a Hb level range within 10 - 12 g/dL and an increase =1.0 g/dL versus the individual patient's baseline Hb level. During the extension period, Hb levels should be maintained between 10 and 12 g/dL.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the efficacy of efepoetin alfa in the treatment of anaemia associated with CKD as measured by haemoglobin (Hb) response rate at the end of correction treatment evaluation period - Measurement is done by an increase in Hb more than or equal to 1 g/dL compared with baseline and a Hb concentration within range of 10 - 12 g/dL inclusive without transfusion during evaluation period
Timepoint [1] 0 0
Measurement from the date of Randomization till the End of the Corrective Treatment period, assessed up to 20 weeks.
Secondary outcome [1] 0 0
Characterise safety and tolerability of subcutaneous efepoetin alfa is being measured by based on the frequency of adverse events and on the number of out of range laboratory values. - Safety endpoints parameters including Serious Adverse Events (SAE) specified below
Composite outcome of cardiovascular death or a nonfatal myocardial infarction or stroke
All-cause mortality
Cardiovascular mortality
Acute myocardial infarction
Heart failure
Acute kidney injury defined according to Acute Kidney Injury Network (AKIN) criteria
Abnormal clinical laboratory tests (haematology, biochemistry including serum ferritin and TSAT)
Anti-efepoetin alfa or anti-Mircera antibody titres
Clinically meaningful abnormal findings of vital signs
Development of clinically meaningful electrocardiogram abnormalities
Hospitalisations (excluding those for logistic reasons)
It is a composite outcome. Any abnormal test findings during the study will be helpful in reviewing the outcome.
Timepoint [1] 0 0
Measurement from the time the subject provides informed consent through and including 28 calendar days after the last study drug administration.

Eligibility
Key inclusion criteria
1. Age should be greater than or equal to the minimum age of consent in the applicable
country

2. Stage 3 or 4 CKD (eGFR = 15 and < 60 mL/min/1.73 m2)

3. ESA-naive (no prior ESA use) subjects whose Hb at baseline is = 8 g/dL and < 10 g/dL,
or ESA prior users whose Hb at baseline is = 8 g/dL and < 10 g/dL and who have stopped
using ESA at least 12 weeks till the screening

4. Ferritin = 100 ng/mL and transferrin saturation (TSAT) = 20%

5. Subject must be willing to complete all study-related activities and follow-up visits

6. Evidence of a signed and dated informed consent document indicating that the subject
has been informed of all pertinent aspects of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Need for dialysis therapy expected in the next 12 months or rapid progression of CKD
(e.g., eGFR decrease of >20% within 12 weeks)

2. Received a blood transfusion (including RBC transfusion) within the 12 weeks prior to
screening, or blood transfusion is anticipated during the study period

3. Have a history of overt gastrointestinal bleeding or any other bleeding episode
associated with a fall in Hb of = 1 g/dL, within the last 8 weeks prior to screening

4. Have an unstable Hb for any reason, in the investigator's opinion

5. Have non-renal anaemia (any anaemia where the investigator considers the anaemia is
predominantly due to a non-renal cause. Non-renal causes include, but are not limited
to vitamin B12 or folic acid deficiency, homozygous sickle-cell disease, thalassemia
of all types, other non-renal cause of anaemia such as myelodysplasia or
haematological malignancies)

6. Platelet count of = 50 x109/L

7. Vitamin B12 deficiency defined as total serum levels of < 181 pmol/L (246 pg/ml) 10

8. Folic acid deficiency defined as total serum levels < 7.63 nmol/L (3.37 ng/mL) 10

9. Pure red cell aplasia, or a history of pure red cell aplasia

10. Poorly controlled hypertension defined as a sitting SBP =170 mmHg and/or DBP =100 mm
Hg

11. Chronic congestive heart failure (New York Heart Association class IV) or are
otherwise at high risk for early withdrawal or interruption of the study (due to
myocardial infarction, severe or unstable coronary artery disease, stroke, or severe
liver disease) within the 12 weeks before screening or during screening

12. Active or not active malignancy (except non-melanoma skin cancer) within five years
before screening

13. Planned live kidney transplantation scheduled within 52 weeks after the screening
visit

14. Uncontrolled hyperparathyroidism, in the investigator's opinion

15. Uncontrolled hypothyroidism determined by the investigator that they cannot
participate in the study

16. Active acute or chronic infection, or uncontrolled or symptomatic inflammatory disease
(e.g., rheumatoid arthritis, systemic lupus erythematosus), or a C-reactive protein
level > 15 mg/L. (Routinely screening for hepatitis B virus (HBV), hepatitis C virus
(HCV), and human immunodeficiency virus (HIV) infection is not required in this
protocol. By history or current clinical evidence, patients with active acute HBV or
HCV infection should be excluded. Chronic HBV/HCV infection with LFTs > 3 times of
normal are excluded. Known HIV positive patients are excluded)

17. Immunosuppressive therapy (other than corticosteroids for a chronic condition, or
tacrolimus/cyclosporine) within 12 weeks prior to baseline

18. Life expectancy of less than 52 weeks

19. Planned surgery during the study period (excluding minor skin excisions)

20. Have received investigational drug(s) other than those of this study within 4 weeks
prior to screening, or will receive investigational drug(s) other than those of this
study during the study period

21. History or clinical evidence of cardiovascular, haematologic or hepatic (ALT, AST,
bilirubin values above three times the upper limit of normal [ULN] at screening) or
any physical conditions that, in the opinion of the investigator, would compromise
participation in the study

22. With a cognitive or psychiatric condition rendering the subject unable to be
cooperative with and complete study requirements

23. Hypersensitivity to any one of the investigational drugs

24. Subjects are, in the judgement of the investigator, otherwise inappropriate for entry
into the study

25. Subjects who are investigational site staff members directly involved in the conduct
of the trial and their family members, site staff members otherwise supervised by the
Investigator, or subjects who are KGBio or CRO employees directly involved in the
conduct of the trial

26. Participation in other studies involving same investigational drug(s) (Phases 1-4) of
this study within 12 weeks before screening

27. Females of childbearing potential or males who are unable/unwilling to take adequate
contraceptive precautions defined by the protocol for the duration of the study and
for at least 28 days after last dose of investigational product. Females have a
positive pregnancy test result within 24 hours prior to study entry, is otherwise
known to be pregnant, plans to become pregnant in the next 12 months or is currently
breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS
Recruitment hospital [1] 0 0
Renal Research Gosford - Gosford
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Launceston General Hospital - Launceston
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
7250 - Launceston
Recruitment outside Australia
Country [1] 0 0
Malaysia
State/province [1] 0 0
Perak
Country [2] 0 0
Malaysia
State/province [2] 0 0
Selangor
Country [3] 0 0
Malaysia
State/province [3] 0 0
Ipoh
Country [4] 0 0
Malaysia
State/province [4] 0 0
Kajang
Country [5] 0 0
Malaysia
State/province [5] 0 0
Kota Bharu
Country [6] 0 0
Malaysia
State/province [6] 0 0
Kuala Lumpur
Country [7] 0 0
Malaysia
State/province [7] 0 0
Kuantan
Country [8] 0 0
Malaysia
State/province [8] 0 0
Serdang
Country [9] 0 0
Malaysia
State/province [9] 0 0
Sibu
Country [10] 0 0
Philippines
State/province [10] 0 0
Bacolod City
Country [11] 0 0
Philippines
State/province [11] 0 0
Baguio
Country [12] 0 0
Philippines
State/province [12] 0 0
Cebu City
Country [13] 0 0
Philippines
State/province [13] 0 0
Dasmariñas
Country [14] 0 0
Philippines
State/province [14] 0 0
Davao City
Country [15] 0 0
Philippines
State/province [15] 0 0
Iloilo City
Country [16] 0 0
Philippines
State/province [16] 0 0
Quezon
Country [17] 0 0
Taiwan
State/province [17] 0 0
Changhua
Country [18] 0 0
Taiwan
State/province [18] 0 0
Hualien City
Country [19] 0 0
Taiwan
State/province [19] 0 0
Kaohsiung
Country [20] 0 0
Taiwan
State/province [20] 0 0
Keelung
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taichung
Country [22] 0 0
Taiwan
State/province [22] 0 0
Tainan
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei
Country [24] 0 0
Taiwan
State/province [24] 0 0
Taoyuan
Country [25] 0 0
Thailand
State/province [25] 0 0
Bangkok
Country [26] 0 0
Thailand
State/province [26] 0 0
Chiang Mai
Country [27] 0 0
Thailand
State/province [27] 0 0
Pathum Thani
Country [28] 0 0
Thailand
State/province [28] 0 0
Songkhla
Country [29] 0 0
Thailand
State/province [29] 0 0
Ubon Ratchathani

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
PT Kalbe Genexine Biologics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, randomised, multicenter, Mircera-controlled, parallel-group, Phase III
study to determine whether subcutaneous administered efepoetin alfa is as effective and well
tolerated as subcutaneous Mircera for anaemia correction and maintenance in erythropoiesis
stimulating agent (ESA)-naïve subjects who have CKD and are not on dialysis. ESA prior users
who have stopped using ESA at least 12 weeks till screening will also be eligible for this
study provided they fulfil all the subject entry criteria.
Trial website
https://clinicaltrials.gov/show/NCT04155125
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Srinivas Rao Jada
Address 0 0
Country 0 0
Phone 0 0
+6598474170
Fax 0 0
Email 0 0
jada.rao@kalbe.co.id
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04155125