Condition category
Urological and Genital Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

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

Trial website

Contact information



Primary contact

Dr Chris Freitag


Contact details

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

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

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

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.

Study design

Phase III open-label uncontrolled international multicentre study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Chronic Kidney Disease (CKD)


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



Phase III

Drug names

HMR4396, a gene-activated erythropoietin

Primary outcome measure

The primary efficacy endpoint in this study was the determination of each subject’s 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 trial start date


Overall trial end date


Reason abandoned (if study stopped)


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 type


Age group




Target number of participants

865 subjects were screened of which 478 received HMR4396

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


Recruitment end date



Countries of recruitment

France, Germany, United Kingdom, United States of America

Trial participating centre

Shire Pharmaceuticals contact for trial
RG24 8EP
United Kingdom

Sponsor information


Hoechst Marion Roussel (Shire Pharmaceuticals) (France)

Sponsor details

102 Route de Noisy

Sponsor type




Funder type


Funder name

Hoechst Marion Roussel (France)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/09/2016: No publications found in PubMed, verifying study status with principal investigator.