An Efficacy Study for Epoetin alfa in Anemic Patients with Myelodysplastic Syndromes

• Register: EUCTR
• Last refreshed on: 23 January 2017
• Main ID: EUCTR2010-022884-36-BG
• Date of registration: 26/04/2013
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: An Efficacy Study for Epoetin alfa in Anemic Patients with Myelodysplastic Syndromes
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating Epoetin Alfa Versus Placebo in Anemic Patients with IPSS Low- or intermediate 1 Risk Myelodysplastic Syndromes
• Date of first enrolment: 12/06/2013
• Target sample size: 159
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022884-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, France, Germany, Greece, Italy, Russian Federation

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subject at least 18 years of age;

2. Criterion modified per amendment;
2.1. Criterion modified per amendment;
2.2. Diagnosis of MDS according to WHO or FAB pathologic classification (confirmed via bone marrow aspirate/biopsy) within 12 weeks prior to screening/during screening phase;
Note: If there is any sign of disease progression, a bone marrow
aspirate/biopsy should be repeated during the screening phase.

3. Criterion modified per amendment;
3.1. Criterion modified per amendment.
3.2. Documentation of an IPSS score indicating Low- or Intermediate-1-risk disease within 12 weeks prior to screening/during screening phase;
Note: If there is no sign of disease progression, an IPSS score based on bone marrow sample obtained up to 12 weeks before screening can be used for documentation.

4. Criterion modified per amendment;
4.1. Criterion modified per amendment;
4.2. Hemoglobin concentration at screening and baseline (before the first dose of study drug) of 10.0 g/dL or less;
Note: Assessment should be based on untransfused hemoglobin, ie, the subject did not receive a RBC transfusion within the previous 2 weeks (if the subject was transfused within 2 weeks before screening or between screening and baseline a maximum hemoglobin concentration of 10.5 g/dL at screening
or at baseline is acceptable).

5. Criterion modified per amendment
5.1 Screening serum erythropoietin concentration of less than 500 mU/mL; Note: Any subject with screening serum erythropoietin concentration >500 mU/mL can be retested once if the investigator has reason to believe that this is an unusual erythropoietin concentration for the subject.


6. Criterion modified per amendment;
6.1. RBC transfusion requirement of less than or equal to 4 RBC units over the last 8 weeks before randomization;

7. Screening Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;

8. Adequate iron stores, defined as serum ferritin greater than 100 ng/mL, transferrin saturation greater than 20%, or both, measured within the 2-week screening period, or adequate iron stores as demonstrated by recent (within 12 weeks) bone marrow examination with iron stain;

9. Criterion modified per amendment;
9.1 Documentation of adequate vitamin B12 and folate levels (above the lower limit of the reference range for the laboratory performing the assay), measured at screening and/or baseline.
Note: If the levels are below the lower limit at screening, and the subject has a confirmed diagnosis of MDS based on the bone marrow sample, subjects may be resupplied with vitamin B12 and/or folate during the screening period (resupply should be started without delay) and have levels retested so that the
results would be available at baseline (before randomization); such subjects with adequate levels from results available at baseline will be eligible for enrollment.

10. Female subjects with reproductive potential must be surgically sterile, abstinent, or practicing an effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, male partner sterilization) before entry and throughout the study and have a negative urine or serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening (all female subjects with reproductive potential) and at Week 24 (female subjects with reproductive potential continuing in the
Exclusion criteria:
1. Anemia attributed to factors other than MDS (including hemolysis, chronic renal failure, hepatitis, gastrointestinal bleeding);

2. Secondary MDS (ie, MDS arising after chemotherapy, immunotherapy or radiation therapy/exposure);

3. Criterion modified per amendment;
3.1. History of malignancy except in situ skin basal cell carcinoma or carcinoma in situ of the cervix or breast curatively treated;

4. Criterion modified per amendment;
4.1 Prior therapy with any ESA (including innovative ESAs and biosimilar ESAs for approved indications or for investigational use) in the last 8 weeks before randomization;

5. Criterion modified per amendment;
5.1 Prior use of approved or experimental agents for the treatment of MDS;
Note: This restriction pertains to agents that are intended to directly influence the proliferation of the malignant clone in the bone marrow and altering the course of the disease (eg, hypomethylating agents, lenalidomide, chemotherapy etc). Different treatments that aim to treat the cytopenias
caused by MDS are not exclusionary in the cases where exclusion criteria 4 and 10 are not met.

6. History (within 6 months) of DVT (including proximal and distal), pulmonary embolism, or other venous thrombosis;Note: prior superficial thrombophlebitis is not an exclusion criterion.

7. Clinically significant, uncontrolled disease or dysfunction of the pulmonary, cardiovascular, endocrine, neurologic, gastrointestinal, or genitourinary systems not attributable to MDS;

8. Criterion modified per amendment;
8.1 Uncontrolled hypertension (defined as a systolic pressure of 160 mmHg or higher, or a diastolic pressure of 110 mmHg or higher, or both); Note: Pertains to a history of uncontrolled hypertension, as reported by the subject or their physician (eg, general practitioner, cardiologist). A single high blood pressure measurement at screening or baseline, which can be
indicative of white coat syndrome, will not be exclusionary.


9. Criterion modified per amendment;
9.1. Use of androgens or corticosteroids for the treatment of MDS within the 2 weeks before screening; androgen or corticosteroid use is allowed for other underlying concomitant diseases (eg, rheumatoid arthritis)

10. Criterion modified per amendment;
10.1. Prior (within 2 weeks before screening) treatment with G-CSF or granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of neutropenia;
Note: in case of neutropenic fever, use of these agents is not an exclusion criterion.

11. Known history of human immunodeficiency virus (HIV) seropositivity;

12. Criterion modified per amendment;
12.1 History (within 6 months before screening) of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, acute coronary syndrome (including myocardial ischemia, unstable angina, Q-wave myocardial infarction, non-Q-wave
myocardial infarction), or other arterial thrombosis;
Note: Subjects with stable angina should be asymptomatic under normal daily effort with or without treatment, there should be no ischemic changes on resting ECG and the onset of the angina should not be within 6months before screening. Subjects who had ischemic heart disease (IHD) but underwent percutaneous transluminal coronary angioplasty (PTCA) are allowed in the
study. It is strongly recommended, when indicated, that subjects who have IHD or have had PTCA be receiving antiaggregant treatment as prophylaxis.

13. Known history of

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Anemic Patients With IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes
MedDRA version: 16.0 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 100000004851

Intervention(s)

Trade Name: ERYPO
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EPOETIN ALFA
CAS Number: 113427-24-0
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 40,000-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: The secondary objectives include:
- For responders at Week 24, observe the duration of the response through Week 48.
- To assess the proportion of responders at Week 24 maintaining response through Week 48 (as measured by
Erythroid response – IWG 2006).
- To compare time to first RBC transfusion, transfusion-free intervals, and number of RBC units transfused.
- To measure and compare changes in patient-reported outcome (PRO)/quality of life from baseline via the
Functional Assessment of Cancer Therapy - Anemia/Fatigue (FACT-An) and EuroQol 5-dimension (EQ-5D)
questionnaires.
- To collect medical resource utilization data that may be used in future economic modeling (the construction and
reporting of the economic model will be conducted separately from this study).
Overall safety will also be assessed.

Main Objective: To demonstrate that epoetin alfa treatment is better at improving anemia outcome (as evaluated by Erythroid response – International Working Group [IWG] 2006) in subjects with International Prognostic Scoring Systems (IPSS) Low- or Intermediate-1-risk myelodysplastic syndromes (MDS), compared with placebo, through Week 24.

Timepoint(s) of evaluation of this end point: At week 24

Primary end point(s): Erythroid response

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:

1/ Maintenance of Erythroid response

2/ Duration of response

3/ Time to first Red Blood Cell transfusion

4/ Transfusion-free intervals

5/ Number of Red Blood Cell units transfused

6/ Quality of life as measured by Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) questionnaire

7/ Quality of life as measured by EuroQol 5-dimension (EQ-5D) questionnaire

8/ Drug Consumption

9/ Duration of Hospitalization

10/ Number and duration of medical care encounters

Timepoint(s) of evaluation of this end point: 1/ every 4 weeks from week 24 to week 48

2/ every 4 weeks after week 24

3/ from baseline to study end (week 28 for non
responders, week 54 for responders or 4 weeks after early withdrawal)

4/ from baseline to study end (week 28 for non
responders, week 54 for responders or 4 weeks after early withdrawal)

5/ from baseline to study end (week 28 for non
responders, week 54 for responders or 4 weeks after early withdrawal)

6/ at baseline, week 24 and week 48

7/ at baseline, week 24 and week 48

8/ every 4 weeks from baseline to week 48

9/ every 4 weeks from baseline to week 48

10/ every 4 weeks from baseline to week 48

Secondary ID(s)

2010-022884-36-GR

EPOANE3021

Source(s) of Monetary Support

Janssen Medical Affairs, Turnhoutseweg 30, B-2340 Beerse