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Darbepoetin Alfa in Anemic Low or Intermediate-1 Risk MDS Subjects

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01362140
First received: May 26, 2011
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

This is a Phase 3, multicenter, randomised, double-blind, placebo-controlled trial of darbepoetin alfa 500 μg administered once every 3 weeks (Q3W) to approximately 141 low or intermediate-1 risk anaemic MDS subjects who have not previously received erythropoiesis-stimulating agents (ESAs) or biologic response modifiers to treat MDS. This study consists of a 3-week screening period, a 24-week double-blind treatment period, and a 48-week active treatment period and the long-term follow-up period. An end of treatment period (EOTP) visit occurs at week 25, or 3 weeks after last dose of investigational product (IP) for subjects who withdraw from the study. After entering the active treatment period, an end of active treatment period (EOATP) visit occurs at week 72 / 73, or 3 weeks after the last dose of darbepoetin alfa Q3W (2 weeks after the last dose of darbepoetin alfa administered every 2 weeks [Q2W]) for subjects who withdraw from the study.

Long-term follow-up (LTFU) will occur every 26 weeks (± 4 weeks) from the EOATP visit (or EOTP visit if the subject does not enter the active treatment period) and will continue for a minimum of 3 years from the first dose of IP. Follow-up may occur through clinic visit or telephone contacts. Information on the subject's survival and progression to AML status will be collected during LTFU.

Approximately 141 subjects who meet all eligibility requirements will be randomised in a 2:1 ratio to 1 of 2 groups:

  1. darbepoetin alfa 500 μg Q3W (n=94)
  2. placebo Q3W (n=47)

Randomisation will be stratified by the International Prognostic Scoring System (IPSS) category (low versus intermediate-1) established at screening.


Condition Intervention Phase
MDS
Drug: Darbepoetin alfa
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Multicenter, Randomised, Double-blind, Placebo-controlled Study of Darbepoetin Alfa for the Treatment of Anaemic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • To assess the superiority of darbepoetin alfa versus placebo on the incidence of RBC transfusions during the double-blind treatment period. [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events, including treatment-emergent adverse events of interest (eg, pure red cell aplasia [PRCA]; thrombovascular events (TVE) [arterial thrombovascular events (ATE) and venous thrombovascular events (VTE)]) [ Time Frame: up to 73 weeks ] [ Designated as safety issue: Yes ]
  • Mortality through EOTP, EOATP, and LTFU [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
  • Disease progression to acute myeloid leukemia (AML) through EOTP, EOATP, and LTFU [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
  • Proportion of subjects acheiving International Working Group (IWG) erythroid response during the double-blind treatment period. [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Attaining a clinically meaningful change from baseline to EOTP in FACIT-F: improvement (at least a 3-point increase), deterioration (at least a 3-point decrease), unchanged (less than a 3-point in either direction) [ Time Frame: Up to week 73 ] [ Designated as safety issue: No ]
  • Change in patient-reported fatigue and overall health status from baseline to week 13, EOTP, week 31, week 42/43, week 54/55, and week 72/73/ EOATP as measured by the Functional Assessment of Chronic Illness Therapy (FACIT-F) & EuroQOL-5D [ Time Frame: Up to week 73 ] [ Designated as safety issue: No ]
  • Malignancies other than AML, basal cell carcinoma, or squamous cell carcinoma of the skin through EOTP [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Neutralising antibody formation to darbepoetin alfa [ Time Frame: up to 73 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 147
Study Start Date: December 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Darbepoetin alfa
500 mcg Q3W
Drug: Darbepoetin alfa
500 mcg Q3W
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Q3W

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Low or intermediate-1 risk MDS patients per IPSS at the time of randomisation, as determined by complete blood count (CBC) during screening and bone marrow examination and marrow cytogenetic analysis performed within 16 weeks prior to randomisation. Subject cannot have been rendered low or intermediate-1 risk by prior disease modifying therapy. Bone marrow slides must be available for centralised review at any time throughout the study
  • World Health Organization (WHO) classification of refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS), refractory cytopenias with multilineage dysplasia (RCMD), MDS-unclassified (MDSU), MDS with isolated del(5q) (5q- syndrome) or refractory anaemia with excess blasts-1 (RAEB-1)
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 assessed during screening
  • Haemoglobin level ≤ 10.0 g/dL as assessed by the local laboratory; sample obtained within 7 days prior to randomisation (retest during screening is acceptable)
  • Adequate transferrin saturation (Tsat) (≥ 15%) and serum ferritin (≥ 10 ng/mL) as assessed by the central laboratory during screening (supplementation and retest during screening is acceptable)
  • Adequate serum folate (≥ 4.5 nmol/L [≥ 2.0 ng/mL]) or RBC folate (≥ 317 nmol/L [≥ 140 ng/mL]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable)
  • Adequate vitamin B12 (≥ 148 pmol/L [≥ 200 pg/mL]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable)
  • 18 years of age or older
  • Subject or subject's legally acceptable representative has provided informed consent -

Exclusion Criteria:

  • Previously diagnosed with intermediate-2 or high risk MDS per International Prognostic Scoring System (IPSS)
  • Therapy-related or secondary MDS
  • History of acute leukemia
  • Evidence of bone marrow collagen fibrosis
  • Inherited anaemia (eg, haemoglobinopathy, thalassemia, red cell membrane defect, red cell enzyme deficiency), active hemorrhage, red cell aplasia, haemolytic anaemia
  • History of malignancies other than curatively treated non-melanoma skin or in situ carcinoma
  • History of thrombosis within 6 months prior to randomisation
  • Previous bone marrow or stem cell transplantation
  • Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to randomisation
  • Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at screening
  • Clinically significant systemic infection or uncontrolled chronic inflammatory disease (ie, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator at screening
  • History of seizure disorder (subject with previous history of seizure disorder will be eligible for the study if he/she had no evidence of seizure activity within 5 years of randomisation and is currently free of antiseizure medication)
  • Previous or ongoing use of ESA therapy, eg, rHuEpo, darbepoetin alfa
  • High transfusion demand: receiving a total of ≥ 4 units of RBC transfusion during either of 2 consecutive 8-week periods (ie, days -113 to -57 or days -56 to 0) prior to randomisation
  • Received any RBC transfusion within 14 days prior to randomisation
  • Received cytotoxic chemotherapy for any oncologic indication or planning to receive cytotoxic chemotherapy during the double-blind treatment period of the study
  • Received biologic response modifiers (eg, thalidomide, lenalidomide, arsenic trioxide, azacitidine, decitabine) to treat MDS or planning to receive biologic response modifiers during the double-blind treatment period of the study
  • Received myeloablative or craniospinal radiation or planning to receive myeloablative or craniospinal radiation during the double-blind treatment period of the study
  • Received G-CSF therapy within 30 days prior to randomisation or planning to receive G-CSF therapy during the double-blind treatment period of the study (temporary use of G-CSF for neutropenia with fever and/or infection is acceptable)
  • Abnormal renal function (serum creatinine level > 2 times the upper limit of the respective normal range [ULN]) as assessed by the central laboratory at screening
  • Abnormal liver function (total bilirubin > 2 times, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times ULN) as assessed by the central laboratory at screening. (Subjects with abnormal bilirubin at screening due to documented Gilbert's Disease are eligible if all other criteria are met.)
  • Serum endogenous erythropoetin (EPO) level > 500 mU/mL as assessed by the central laboratory at screening
  • Known seropositivity for human immunodeficiency virus (HIV) or diagnosis of Acquired Immunodeficiency Syndrome (AIDS), positive for hepatitis B surface antigen, or seropositive for hepatitis C virus
  • Subjects with active ethanol abuse, as judged by the investigator
  • Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
  • Female subject is not willing to use highly effective contraception during treatment and for at least 1 month after the end of treatment
  • Female subject is pregnant or planning to become pregnant within 1 month after the end of treatment
  • Subject has known sensitivity to any of the products to be administered during dosing
  • Subject has previously been randomised into this study
  • Subject will not be available for protocol-required study visits, to the best of the subject and investigator's knowledge
  • Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
  • Confirmed history of neutralising antibody activity to rHuEpo or darbepoetin alfa
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01362140

  Show 72 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01362140     History of Changes
Other Study ID Numbers: 20090160
Study First Received: May 26, 2011
Last Updated: September 11, 2014
Health Authority: Greece: National Organization for Medicines
Spain: Spanish Agency of Medicines
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Germany: Bundesinstitut für Arzneimitel und Medizinprodukte (BfArM)
Italy: Local Ethics committees
Czech Republic: Statni ustav pro kontrolu leciv (SUKL)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Austria: Bundesamt für Sicherheit im Gesundheitswesen AGES - PharmMed

Keywords provided by Amgen:
Randomized
Darbepoetin alfa
Myelodysplastic Syndromes
Placebo-controlled
low risk MDS
intermediate-1 risk MDS
International Prognostic Scoring System

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Precancerous Conditions
Darbepoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014