Darbepoetin Alfa MDS Companion Protocol
Study Details
Study Description
Brief Summary
The primary objective of the study was to provide required access of investigational product (darbepoetin alfa) beyond the end of the active treatment period (EOATP) of the darbepoetin alfa MDS 20090160 (NCT01362140) study for patients who had continued demonstration of benefit from darbepoetin alfa treatment and to describe the safety of longer-term use in this patient population.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a phase 3b, multi-centre, open-label, single-arm companion study to the MDS 20090160 study (NCT01362140) for the treatment of anaemic patients with MDS. Participants who completed the active-treatment period of the darbepoetin alfa MDS 20090160 study and met the eligibility criteria could be enrolled into this study to continue treatment of darbepoetin alfa for up to 73 weeks or until progression to acute myelogenous leukemia (AML), whichever occurs first.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Darbepoetin Alfa Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. |
Drug: Darbepoetin Alfa
The first dose of darbepoetin alfa was the same as that administered at the last dosing visit of the active treatment period in Study 20090160. Doses could be increased up to a maximum of 500 μg every two weeks (Q2W).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-emergent Adverse Events [From first dose of darbepoetin alfa to 30 days after last dose; the maximum treatment duration was 73 weeks.]
Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 indicates a mild AE, Grade 2 indicates a moderate AE, Grade 3 indicates severe or medically significant but not immediately life-threatening and Grade 4 indicates life-threatening consequences; urgent intervention indicated. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: fatal life threatening required in-patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event The investigator assessed whether each adverse events was related to darbepoetin alfa.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subject or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/ procedures being initiated;
-
Subject must continue long term follow up within parent study (20090160);
-
Subject must have an ongoing clinically relevant erythroid response as assessed by the Investigator using current response criteria (ie, International Working Group (IWG) response criteria);
Exclusion Criteria:
-
Transfusion dependence defined as receiving a total of ≥ 4 units of red blood cell (RBC) transfusion in the previous 8-week period prior to enrolment;
-
Known diagnosis of acute myelogenous leukemia (AML) or marrow collagen fibrosis;
-
Known refractory anaemia with excess blast-2 (RAEB-2);
-
Known diagnosis of intermediate-2 or high risk MDS per International Prognostic Scoring System (IPSS);
-
Subjects received thrombopoiesis-stimulating factors (eg, eltrombopag, romiplostim) in the MDS 20090160 study or planning to receive such agents during the study;
-
Other protocol defined inclusion and exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Charleroi | Belgium | 6000 | |
| 2 | Research Site | Leuven | Belgium | 3000 | |
| 3 | Research Site | Liege | Belgium | 4000 | |
| 4 | Research Site | Sint-Niklaas | Belgium | 9100 |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 20130113
- 2013-000727-13
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 5 centers in Belgium from 12 June 2014 (first participant enrolled) to 20 March 2017 (last participant completed study). |
|---|---|
| Pre-assignment Detail | This study enrolled participants who completed the active treatment period of the phase 3 Study 20090160 (NCT01362140). |
| Arm/Group Title | Darbepoetin Alfa |
|---|---|
| Arm/Group Description | Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. |
| Period Title: Overall Study | |
| STARTED | 9 |
| COMPLETED | 8 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Darbepoetin Alfa |
|---|---|
| Arm/Group Description | Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. |
| Overall Participants | 9 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
71.3
(7.9)
|
| Age, Customized (Count of Participants) | |
| 18 - 64 years |
1
11.1%
|
| 65 - 74 years |
6
66.7%
|
| 75 - 84 years |
2
22.2%
|
| ≥ 85 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
33.3%
|
| Male |
6
66.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
1
11.1%
|
| Not Hispanic or Latino |
8
88.9%
|
| Unknown or Not Reported |
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| White |
9
100%
|
Outcome Measures
| Title | Number of Participants With Treatment-emergent Adverse Events |
|---|---|
| Description | Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 indicates a mild AE, Grade 2 indicates a moderate AE, Grade 3 indicates severe or medically significant but not immediately life-threatening and Grade 4 indicates life-threatening consequences; urgent intervention indicated. A serious adverse event was defined as an adverse event that met at least one of the following serious criteria: fatal life threatening required in-patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event The investigator assessed whether each adverse events was related to darbepoetin alfa. |
| Time Frame | From first dose of darbepoetin alfa to 30 days after last dose; the maximum treatment duration was 73 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants |
| Arm/Group Title | Darbepoetin Alfa |
|---|---|
| Arm/Group Description | Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. |
| Measure Participants | 9 |
| All adverse events |
9
100%
|
| Adverse events ≥ grade 2 |
8
88.9%
|
| Adverse events ≥ grade 3 |
2
22.2%
|
| Adverse events ≥ grade 4 |
0
0%
|
| Serious adverse events |
3
33.3%
|
| AEs leading to discontinuation of darbepoetin alfa |
1
11.1%
|
| Fatal adverse events |
0
0%
|
| Treatment-related adverse events |
0
0%
|
Adverse Events
| Time Frame | From first dose of darbepoetin alfa to 30 days after last dose; the maximum treatment duration was 73 weeks. | |
|---|---|---|
| Adverse Event Reporting Description | Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. | |
| Arm/Group Title | Darbepoetin Alfa | |
| Arm/Group Description | Participants received darbepoetin alfa for up to 73 weeks or until progression to acute myeloid leukemia (AML), whichever occurred first. | |
All Cause Mortality |
||
| Darbepoetin Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | |
Serious Adverse Events |
||
| Darbepoetin Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/9 (33.3%) | |
| Eye disorders | ||
| Macular fibrosis | 1/9 (11.1%) | |
| General disorders | ||
| Pyrexia | 1/9 (11.1%) | |
| Nervous system disorders | ||
| Ischaemic stroke | 1/9 (11.1%) | |
Other (Not Including Serious) Adverse Events |
||
| Darbepoetin Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/9 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 2/9 (22.2%) | |
| Neutropenia | 1/9 (11.1%) | |
| Cardiac disorders | ||
| Palpitations | 1/9 (11.1%) | |
| Eye disorders | ||
| Chalazion | 1/9 (11.1%) | |
| Visual acuity reduced | 1/9 (11.1%) | |
| Gastrointestinal disorders | ||
| Abdominal discomfort | 3/9 (33.3%) | |
| Abdominal pain | 1/9 (11.1%) | |
| Abdominal pain upper | 1/9 (11.1%) | |
| Aphthous ulcer | 1/9 (11.1%) | |
| Diarrhoea | 1/9 (11.1%) | |
| Dry mouth | 1/9 (11.1%) | |
| Haematochezia | 1/9 (11.1%) | |
| Inguinal hernia | 1/9 (11.1%) | |
| Nausea | 1/9 (11.1%) | |
| Vomiting | 1/9 (11.1%) | |
| General disorders | ||
| Asthenia | 1/9 (11.1%) | |
| Fatigue | 4/9 (44.4%) | |
| Injection site haematoma | 1/9 (11.1%) | |
| Malaise | 1/9 (11.1%) | |
| Pyrexia | 1/9 (11.1%) | |
| Infections and infestations | ||
| Bronchitis | 1/9 (11.1%) | |
| Gingivitis | 1/9 (11.1%) | |
| Herpes simplex | 1/9 (11.1%) | |
| Influenza | 1/9 (11.1%) | |
| Nasopharyngitis | 2/9 (22.2%) | |
| Oral fungal infection | 1/9 (11.1%) | |
| Pharyngitis | 1/9 (11.1%) | |
| Sinusitis | 1/9 (11.1%) | |
| Upper respiratory tract infection | 1/9 (11.1%) | |
| Urinary tract infection | 1/9 (11.1%) | |
| Injury, poisoning and procedural complications | ||
| Contusion | 1/9 (11.1%) | |
| Fall | 1/9 (11.1%) | |
| Upper limb fracture | 1/9 (11.1%) | |
| Investigations | ||
| Blood creatinine increased | 1/9 (11.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 1/9 (11.1%) | |
| Bone pain | 2/9 (22.2%) | |
| Hypercreatinaemia | 1/9 (11.1%) | |
| Muscle spasms | 1/9 (11.1%) | |
| Musculoskeletal chest pain | 1/9 (11.1%) | |
| Pain in extremity | 1/9 (11.1%) | |
| Nervous system disorders | ||
| Dizziness | 2/9 (22.2%) | |
| Headache | 2/9 (22.2%) | |
| Restless legs syndrome | 1/9 (11.1%) | |
| Psychiatric disorders | ||
| Depression | 1/9 (11.1%) | |
| Renal and urinary disorders | ||
| Nocturia | 1/9 (11.1%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 3/9 (33.3%) | |
| Dysphonia | 1/9 (11.1%) | |
| Dyspnoea | 1/9 (11.1%) | |
| Dyspnoea exertional | 4/9 (44.4%) | |
| Epistaxis | 1/9 (11.1%) | |
| Oropharyngeal pain | 3/9 (33.3%) | |
| Rhinorrhoea | 1/9 (11.1%) | |
| Skin and subcutaneous tissue disorders | ||
| Erythema | 1/9 (11.1%) | |
| Pruritus | 1/9 (11.1%) | |
| Rash | 1/9 (11.1%) | |
| Rash generalised | 1/9 (11.1%) | |
| Skin discomfort | 1/9 (11.1%) | |
| Urticaria | 1/9 (11.1%) | |
| Vascular disorders | ||
| Haematoma | 1/9 (11.1%) | |
| Hypotension | 1/9 (11.1%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
- 20130113
- 2013-000727-13