CTRI/2022/06/042974 [Registered on: 02/06/2022] Trial Registered Prospectively
Last Modified On:
09/08/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Non-randomized, Placebo Controlled Trial
Public Title of Study
To Evaluate the Efficacy and Safety of Ferric Pyrophosphate Citrate Administered via Dialysate to Maintain Hemoglobin Concentration in Chronic Kidney Disease Patients Receiving Hemodialysis (a procedure where a dialysis machine or a dialyzer are used to clean your blood)
Scientific Title of Study
A Phase 3, Multicenter, Randomized, Single-blind, Placebo-controlled, Parallel-arm Study to Evaluate the Efficacy and Safety of Ferric Pyrophosphate Citrate Administered via Dialysate to Maintain Hemoglobin Concentration in Chronic Kidney Disease Patients Receiving Hemodialysis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ICR/21/010; Version no.: 3.0, dated 02/FEB/2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Suyog Mehta
Designation
Vice President & Head - Medical Affairs & Clinical Research, India & EM
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
suyog.mehta@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Sapan Behera
Designation
MBBS, MD, DM
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
sapan.behera@sunpharma.com
Details of Contact Person Public Query
Name
Rajesh Gaikwad
Designation
Deputy General Manager – India Clinical Research
Affiliation
Sun Pharma Laboratories Limited
Address
Sun Pharma Laboratories Limited,
Sun House, Plot No. 201 B/1, Western Express Highway,
Goregaon (E), Mumbai-400063, Maharashtra, India
Mumbai MAHARASHTRA 400063 India
Phone
02243244324
Fax
02243244343
Email
rajesh.gaikwad@sunpharma.com
Source of Monetary or Material Support
Sun Pharma Laboratories Limited
Sun House, 201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063
Primary Sponsor
Name
Sun Pharma Laboratories Limited
Address
Sun House, 201 B/1, Western Express Highway,
Goregaon ( E),Mumbai 400 063
All India Institute of Medical Sciences, MIHAN, Sumthana, Nagpur- 441108 Nagpur MAHARASHTRA
8800905030
amolbhawane@gmail.com
Dr Vinay Rathod
All India Institute Of Medical Sciences
All India Institute Of Medical Sciences, Department of Nephrology, ground floor, OPD No. 1, D BLOCK, G.E. Road , Tatibandh , Raipur Chhattisgarh-492099. Raipur CHHATTISGARH
9057279574
vinayrathoredm@aiimsraipur.edu.in
Dr Siddharth Mavani
Avishkar Dialysis Centre
Avishkar Dialysis Centre, Nijanandnagar, Motipura, Himmatnagar-383001, Gujarat Sabar Kantha GUJARAT
9825317953
msiddh@yahoo.co.in
Dr Chaudhari Avinash Eknathrao
Dr. D.Y. Patil Medical College Hospital & Research Centre
OPD building, Department of Nephrology, Dr. D.Y. Patil Medical College Hospital & Research Centre, Plot no. 2, Sector -5, Nerul, Navi Mumbai-400706 Mumbai MAHARASHTRA
9820047661
achaudhari12@yahoo.co.in
Dr Patil Mayur Vinayakrao
Dr. M.K Shah Medical College & Research Centre
Room No 04, Medicine OPD, Dr. M.K Shah Medical College & Research Centre, Smt S.M.S. Multispecialty Hospital, Ahmedabad -382424 Ahmadabad GUJARAT
9727765779
mayurpatil20@gmail.com
Dr Sanjay S
Dr. Sanjay Hospital
Dr. Sanjay Hospital, Dr. Sanjays Centre for Kidney & Diebetes, Ground floor, Dept. of Nephrology, 357/B, Bangalore- Bellari Road, parallel to new airport rd, Old town, Yalahanka, Bangalore 560064. Bangalore KARNATAKA
Second floor, Department of Medicine, Government Medical College and Hospital, Panchakki Road, Aurangabad- 431001 Aurangabad MAHARASHTRA
9922931527
mabhattacharya@gmail.com
Dr Vidyasagar Korla
Govt. Medical College & Government General hospital
Department of Medicine, OPD no. 13, 1st floor, Govt. Medical College & Government General hospital (Old RIMSGGH), Srikakulam- 532001, Andhra Pradesh, India Srikakulam ANDHRA PRADESH
9491191631
drvidyasagarkggh@gmail.com
Dr Vajid Rahim
Ishwar Institute of Health Care
Ishwar Institute of Health Care, Ishwar Heights, 1st Floor Plot No. 7,gut no 6/1 , beside Punjabi Bhavan, Padegaon, Aurangabad-431002 Maharashtra India. Aurangabad MAHARASHTRA
Kins Care and Research foundation
Jhankar More, 1st floor, Golden height building, Siliguri, West Bengal- 734005
Darjiling WEST BENGAL
9434001422
dr.schakraborty365@gmail.com
Dr Niranjan MR
KR Hospital Attached to Mysore Medical College and Research
KR Hospital Attached to Mysore Medical College and Research Institute, Room no 4, Department of Nephrology, KR Hospital Attached to Mysore Medical College and Research institute, Irwin Road, Mysuru, Karnataka, India- 570001. Mysore KARNATAKA
9448672501
drniranjanmr@gmail.com
Dr Tarun Jeloka
Life Point Multispecialty Hospital
3rd Floor, Clinical Research Department, Life Point Multispecialty Hospital ,145/1, Mumbai Bangalore Highway , Near Hotel Sayaji, Wakad Pune-411057- Maharashtra India. Pune MAHARASHTRA
9370691221
tjeloka@gmail.com
Dr Dinesh Mittal
Maharaja Agrasen hospital
Maharaja Agrasen hospital, West Punjabi Bagh, New Delhi- 110026 New Delhi DELHI
9811140304
dmnephro@gmail.com
Dr Bahadur Madan Mohan
Masina Hospital Trust
Masina Hospital Trust Sant Savta Marg, Byculla (East) Mumbai Mumbai City Maharashtra - 400027 India Mumbai MAHARASHTRA
9821083965
madan.bahadur@gmail.com
Dr Avinash Ignatius
Noble Hospital
2nd Floor, OPD No. 1, Nephrology Department, Noble Annex Building, Magarpatta City Road, Hadapar, Pune, Maharashtra, India, 411013. Pune MAHARASHTRA
9823101982
dr_ignatius@yahoo.co.in
Prof Dr Pinaki Mukhopadhayay
NRS Hospital
Dept. of Nephrology, NRS Hospital, Nil Ratan Sircar Medical College & Hospital, 138 ,A.J.C. Bose Road ,Kolkata 700014 , West Bengal India. Kolkata WEST BENGAL
9231978078
drpinaki71@yahoo.com
Dr Pradeep Kumar Rai
Opal Hospital Private Limited
Opal Hospital Private Limited, Ground floor, Department of Nephrology, Room No. 3, N 10/60-2 Kakarmatta DLW Road Varanasi Varanasi Uttar Pradesh – 221002. Varanasi UTTAR PRADESH
9336913486
pradeepk.rai@gmail.com
Dr Manisha Kumar Sahay
Osmania Medical College & General Hospital
Osmania Medical College & General Hospital, Professor and HOD, Department of Nephrology. QQDC Building 3rd Floor Room No.447, Afzalgunj, Hyderabad-500012, Telangana, India. Hyderabad TELANGANA
9849097507
drmanishasahay@gmail.com
Dr Vivek Biradar
PCMC’s Yashwantrao Chavan Memorial hospital
2nd floor, Medicine department, PCMC’s Yashwantrao Chavan Memorial hospital, Sant Tukaram Nagar, Pimpri, Pune -411018, Maharashtra Pune MAHARASHTRA
Dept. of Nephrology, Institute of Post Graduate Medical Education & Research, SSKM, I 244 AJC Bose Road, Kolkata-700020, West Bengal, India. Kolkata WEST BENGAL
9433121697
dratanupal@gmail.com
Dr Deodatta Chafekar
Supreme Kidney Care
Supreme Kidney Care, Om Chambers, Sadhu Vaswani Road, Opposite Holaram Colony, Near MICO Circle, Nashik- 422002 Nashik MAHARASHTRA
(1) ICD-10 Condition: D631||Anemia in chronic kidney disease,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Ferric pyrophosphate citrate solution
Ferric pyrophosphate citrate solution will be administered via dialysate during each dialysis session (3 times per week)for 42 weeks.
Comparator Agent
Standard dialysate without FPC
Standard dialysate without FPC will be administered during each dialysis session (3 times per week) for 42 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Adult CKD stage 5 patients of either gender of age ≥ 18 years undergoing chronic hemodialysis at least 3 times per week for at least 3 months prior to screening, and expected to remain on this schedule and able to complete the duration of the study.
2. Patients on minimally adequate measured dialysis dose prior to randomization; defined as urea reduction ratio greater than equal to 65 percentage URR is equal to 1 minus Ureapost-HD divided by Ureapre-HD multiplied by 100, or single-pool Kt by V dialyzer clearance of urea multiplied by dialysis time, divided by patient’s total body water greater than equal to 1.2, or KIDt by V online dialyzer clearance measured using ionic dialysance multiplied by dialysis time, divided by patients total body water greater than equal to 1.2.
3. Dialyzer blood flow rate (QB) prior to randomization ≥ 250 mL/min.
4. Must be willing and able to provide written informed consent directly or through their legally authorized representative (LAR).
5. Received IV iron therapy between 6 months and 2 weeks prior to randomization in order to replace iron losses resulting from hemodialysis procedure.
6. Agree to be ‘without Oral or IV iron supplementation’ from 2 weeks prior to randomization until end-of-treatment (EOT) and ‘no change in ESA dose’ from randomization until EOT by the patient/LAR.
7. Mean screening pre-dialysis Hb ≥ 9.5 to ≤ 11.5 grams per deciliter (g/dL) (i.e., average Hb values of Week -2 & Week -1) at randomization.
8. Mean screening pre-dialysis serum (S.) ferritin ≥ 200 to < 1000 micrograms per liter (µg/L) (i.e., average S. Ferritin values of Week -2 & Week -1) at randomization.
9. Mean screening pre-dialysis Transferrin Saturation (TSAT) ≥ 20% to ≤40% (i.e., average TSAT values of Week -2 & Week -1) at randomization.
10. If being administered erythropoietin stimulating agent (ESA) [epoetin, darbepoetin, or continuous erythropoietin receptor activator (CERA)], the patient should be on stable dose of ESA without change in the route of administration for at least 4 weeks prior to screening. [Stable dose of ESA is defined as the dose change of < 35% (i.e., [maximum [max] – minimum [min] dose]/max dose < 0.35)].
11. Vascular access for dialysis that will be used upon enrollment with stable function in the judgment of the Investigator.
12. Undergoing dialysis only using an arteriovenous (AV) fistula, graft, or tunneled catheter.
13. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period. If currently abstinent, the patients must agree to use a double barrier method as described above if she becomes sexually active during the study period. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
[Note: Women with childbearing potential are defined as: those who are not (1) surgically sterile (bilateral oophorectomy, hysterectomy, or bilateral tubal ligation) or (2) post-menopausal. Post-menopausal woman will be defined as: Woman not using hormonal replacement therapy and have had at least 12 continuous months of natural (spontaneous) amenorrhea and be greater than 45 years of age].
14. Male patients must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period). No sperm donation is allowed during the study period.
ExclusionCriteria
Details
1. Patient who has living kidney donor identified or living-donor kidney transplant scheduled.
2. Vascular access for dialysis with non-tunneled catheter.
3. Patients who are anticipated to be unable to complete the entire study (e.g., due to concurrent disease) based on Investigator’s clinical judgment.
4. Received IV or oral iron therapy within 2 weeks prior to the randomization.
5. Known causes of anemia other than renal failure and HD (e.g., sickle cell disease, thalassemia, pure red cell aplasia, hemolytic anemia, myelodysplastic syndrome, etc.).
6. Known active bleeding from any site other than AV fistula or graft (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.).
7. The patient has any current febrile illness (e.g., oral temperature ≥100.4°F/38.0°C). The patient may subsequently become eligible at least 1 week after resolution of the illness.
8. Planned elective surgery during the study period (from screening to end of the study).
9. Patients with known cirrhosis of liver (based on previously documented histological criteria) or Patients with decompensated liver cirrhosis based on clinical criteria (e.g., presence of ascites, esophageal varices, spider nevi, or history/presence of encephalopathy.
10. RBC or whole blood transfusion within 8 weeks prior to randomization.
11. Patients with serum vitamin B12 and/or serum folic acid deficiency at screening (Note: Retest for serum Vitamin B12 and/or serum folic acid acceptable during screening).
12. Patients having human immunodeficiency virus - human immunodeficiency virus, acquired immunodeficiency syndrome (HIV-AIDS), hepatitis B, C, and Occult /latent tuberculosis (TB) at Screening.
13. Hospitalization in previous three months (except for vascular access surgery) that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of this study.
14. Evidence of any current malignancy except cancers of the skin (either by previously documented laboratory/histological reports or by Investigator’s clinical judgment/suspicion).
15. Known ongoing inflammatory disorder (other than CKD), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease.
16. Known coagulation disorder.
17. Known active bacterial, tuberculosis, fungal, viral, or parasitic infection requiring anti-microbial therapy or anticipated to require anti-microbial therapy during the patient’s participation in this study.
18. Patients with tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient’s participation in this study.
19. Participation in a study of an investigational drug or device within 30 days prior to enrolment in this study, and agree not to participate in any other clinical trial during the study period and up to 30 days after completion of the trial.
20. Patient with a clinically significant condition that in the Investigator’s opinion precludes the patient’s participation in the study or interferes with the interpretation of the study results.
21. History of alcohol or any substance abuse within the last 1 year prior to screening as per Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria.
22. Pregnancy or intention to become pregnant before completing all study drug treatment.
23. Lactating woman.
24. Employee of the Sponsor, Investigator, or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members of the employees of Sponsor or the Investigator.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant Blinded
Primary Outcome
Outcome
TimePoints
Mean change in hemoglobin (Hb) from baseline to End-of-Treatment (EOT).
baseline to End-of-Treatment (EOT).
Secondary Outcome
Outcome
TimePoints
1. Mean change in pre-dialysis serum ferritin
2. Mean change from pre-dialysis to post-dialysis in serum iron and TSAT over the entire randomized treatment period
3. Mean change and mean percentage change in the pre-dialysis reticulocyte hemoglobin content (CHr), serum iron, TSAT, UIBC, and TIBC.
4. The proportion of patients who meet each protocol-mandated anemia management (PMAM) criterion
5. The proportion of completers with Hb 12.5 g/d
6. The proportion of completers with Hb 10 g/dL
7. The proportion of completers with ferritin 100 µg/L
8. Time to achieve end-of-treatment criteria
9. Mean change in High-sensitive C-reactive protein (hs-CRP)
10. Mean change in Interleukin (IL) -6
11. Mean change in hepcidin
12. Proportion of patients receiving RBC or whole blood transfusion
13. Number of units RBC or whole blood transfusion
14. Change in quality-of-life (QoL) score (using dialysis recovery time and/or KDQOL v. 1.3)
1. From baseline to EOT
2. From baseline to EOT
3. From baseline to EOT
4. From baseline to EOT
5. EOT
6. EOT
7. EOT
8. From baseline to EOT
9. From baseline to EOT
10. From baseline to EOT
11. From baseline to EOT
12. From baseline to EOT
13. From baseline to EOT
14. From baseline to EOT
Target Sample Size
Total Sample Size="338" Sample Size from India="338" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
07/06/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="10" Days="1"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Not applicable
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study will be a phase 3, multicenter,
randomized, single-blind, placebo-controlled, parallel-arm study to evaluate efficacy and safety
of FPC dialysate solution administered via dialysate to maintain Hb concentrations in CKD patients
receiving HD.
The study will
be conducted at approximately 25-30 numbers of centers in India, having
qualified Investigators. The study will be initiated only after the receipt of
Regulatory and Ethics committee (EC) approval.
The
study consists of following days of assessments:
·Screening Visit: (Week -2 to Week -1):
Screening
·Treatment Period (Week 1 to Week 42)
ØStudy Initiation Visit (Week 1; 2nd HD session):Randomization, Study drug administration, Baseline parameters
assessment
ØOn Treatment Visit (2nd HD session ofWeek
1 to 2nd HD session of Week 42): Study drug administration, efficacy
and safety parameters assessment
·End of Treatment Visit: 2nd HD
session of Week 42; EOT assessment
·End of study visit/ Follow Up period: From
EOT to 3rd HD session of Week 43; EOS assessment