Safety and efficacy of subcutaneous HMR4396 for the management of anaemia in subjects with chronic renal failure

ISRCTN	ISRCTN68321818
DOI	https://doi.org/10.1186/ISRCTN68321818
Secondary identifying numbers	HMR4396A/3002

Submission date: 25/05/2007
Registration date: 02/07/2007
Last edited: 04/01/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration and not expected to be available in the future

Contact information

Dr Chris Freitag
Scientific

Shire Pharmaceuticals contact for trial
Hampshire International Business Park
Lime Tree Way
Basingstoke
RG24 8EP
United Kingdom

Study information

Study design	Phase III open-label uncontrolled international multicentre study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Safety and efficacy of subcutaneous HMR4396 for the management of anaemia in subjects with chronic renal failure
Study hypothesis	Chronic Kidney Disease (CKD) is often associated with severe anaemia, which is primarily the result of reduced erythropoietin production. Anaemia in patients with CKD is associated with increased morbidity and mortality, and reduced quality of life. Recombinant human erythropoietins can be used to treat anaemia, but existing agents are produced in Chinese Hamster Ovary (CHO) cell lines, leading to a hamster glycosylation profile different from that of endogenous human erythropoietin. HMR4396 is produced in a human cell line, and thus offers a glycosylation profile that differs from that of conventional epoetins. The primary objective was to evaluate the safety and efficacy of subcutaneous HMR4396 in the management of anaemia in subjects with chronic renal failure.
Ethics approval(s)	This was a multi-national, multi-centre trial with 21 centres in the European Union and 27 centres in the United States. The independent ethics committee from each of the sites approved the study before the start date of 1st October 1998.
Condition	Chronic Kidney Disease (CKD)
Intervention	The intervention was administration of HMR4396, given subcutaneously 1, 2, or 3 times weekly for up to 52 weeks, starting at the same dose as the previous epoetin in three patient groups: 1. CKD not on dialysis (pre-dialysis) 2. CKD on haemodialysis 3. CKD on peritoneal dialysis The main comparison was the ability to maintain the Haemoglobin (Hb) concentration over the duration of the trial.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	HMR4396, a gene-activated erythropoietin
Primary outcome measure	The primary efficacy endpoint in this study was the determination of each subjects average haemoglobin concentration (avHGB) over weeks 12, 16, 20, and 24. The primary efficacy analysis of avHGB was performed using the modified Intent-To-Treat (mITT) population. Additional analyses of the primary efficacy endpoint were conducted using the ITT and per-protocol populations. Efficacy analyses were conducted using haematology data collected up to seven days after the last held or received dose of study medication.
Secondary outcome measures	Secondary efficacy endpoints included: 1. Mean treatment dose 2. Mean haematocrit 3. Percentage of haemoglobin values above 10 g/dL 4. Percentage of haematocrit values above 30% 5. Changes in weekly profiles of haemoglobin and haematocrit 6. Counts of red blood cells and reticulocytes Analyses of non-primary endpoints were conducted using both the modified Intent-To-Treat (mITT) and Intent-To-Treat (ITT) populations.
Overall study start date	01/10/1998
Overall study end date	07/06/2000

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	865 subjects were screened of which 478 received HMR4396
Total final enrolment	478
Participant inclusion criteria	1. Men or women, 18 years of age or older, with chronic renal failure 2. Evidence of anaemia (haemoglobin less than 11.0 g/dL) in medical history 3. Subjects receiving hemodialysis must have been prescribed to receive epoetin two or three times weekly by subcutaneous (s.c.) administration for at least 30 days immediately before signing informed consent 4. Predialysis subjects and subjects receiving peritoneal dialysis must have been prescribed to receive epoetin at least once weekly by s.c. administration for at least 30 days immediately before signing informed consent 5. Dose of epoetin not changed by more than 50% (increase or decrease) in the 30 days before signing informed consent 6. Haemoglobin 10.0 to 12.0 (±0.4) g/dL for the two weeks before receiving the first dose of HMR4396 as determined by one measurement per week 7. For predialysis subjects, serum creatinine greater than 2 mg/dL or creatinine clearance less than 45 mL/min as estimated by 24-hour urine collection or Cockcroft and Gault formula 8. Serum ferritin greater than or equal to 90 ng/mL and transferrin saturation greater than or equal to 18% as determined by the pre-study measurement
Participant exclusion criteria	1. Uncontrolled hypertension 2. For haemodialysis subjects, missed more than three dialysis sessions in the 30 days before signing informed consent 3. One or more doses of epoetin missed or withheld by physician order in the 14 days before signing informed consent 4. Concomitant unrelated illness that could reduce life expectancy to less than 12 months (such as malignancy, immune deficiency, myocardial infarction or cerebrovascular accident within 30 days before signing informed consent) 5. Thrombocytopenia (platelet count less than 75,000/mm^3) 6. Active bleeding 7. Treatment with immunosuppressive drugs (other than corticosteroids for a chronic condition) within 30 days before signing informed consent 8. Androgen therapy within 30 days before signing informed consent 9. Current drug abuse 10. Known Human Immunodeficiency Virus (HIV) infection from medical history 11. Treatment with any investigational drug within 30 days before signing informed consent 12. Breastfeeding 13. Pregnancy at enrolment or plans to become pregnant during the study. It was required that absence of pregnancy be documented by serum test before exposure to HMR4396 or any other study procedure with potential risk to a foetus 14. Childbearing potential. Absence of childbearing potential was defined as being surgically sterile, at least one year post-menopausal, or using a medically accepted (prescription or nonprescription) method of contraception 15. History of hypersensitivity to HMR4396 or to drugs with similar chemical structures 16. Impaired hepatic function, defined as a pre-study value for Aspartate Aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase [SGOT]) or Alanine Aminotransferase (ALT) (Serum Glutamic Pyruvic Transaminase [SGPT]) exceeding three times the upper limit of the normal range for the central laboratory 17. Clinically relevant haematologic, cardiovascular, hepatic, neurologic, endocrine, infectious, inflammatory or other major systemic disease making implementation of the protocol or interpretation of the study results difficult 18. Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study 19. Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study 20. Likelihood that the subject would require treatment during the study period with drugs not permitted by the protocol 21. Previous treatment with HMR4396
Recruitment start date	01/10/1998
Recruitment end date	07/06/2000

Locations

Countries of recruitment

England
France
Germany
United Kingdom
United States of America

Study participating centre

Shire Pharmaceuticals contact for trial

Basingstoke
RG24 8EP
United Kingdom

Sponsor information

Hoechst Marion Roussel (Shire Pharmaceuticals) (France)
Industry

102 Route de Noisy
Romainville, Cedex
93235
France

"ROR"	https://ror.org/02n6c9837

Funders

Funder type

Industry

Hoechst Marion Roussel (France)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	25/02/2009	04/01/2021	Yes	No

Editorial Notes

04/01/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
3. The secondary study design has been changed from 'randomised controlled trial' to 'non randomised study'
06/09/2016: No publications found in PubMed, verifying study status with principal investigator.