Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00415532
• Collaborator: (none)
• Enrollment: 234
• Arms: 2
• Actual Duration (Months): 29.3

Study Details

Study Description

Brief Summary

This is a phase 3b, multi-center, randomized, Standard of Care (SOC)-controlled, open-label, 52-week treatment study to compare romiplostim to medical SOC for Idiopathic Thrombocytopenia Purpura (ITP), with a 6-month Safety Follow-up. Patients randomized to romiplostim must complete the taper or discontinuation of medical SOC for ITP as soon as medically feasible after the initiation of romiplostim. After the completion or discontinuation of the study treatment period, any participant who does not transfer in to another romiplostim study will complete a 6-month Safety Follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura	Drug: Medical Standard of Care for ITP; Biological: Romiplostim	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 234 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled, Open-label Study Evaluating the Efficacy and Tolerability of AMG 531 Versus Medical Standard of Care as Chronic Therapy for Non-splenectomized Subjects With Immune (Idiopathic) Thrombocytopenic Purpura
• Actual Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Nov 7, 2008
• Actual Study Completion Date: May 11, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Romiplostim Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.	Biological: Romiplostim; Other Names: AMG 531
Other: Standard of Care Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Drug: Medical Standard of Care for ITP

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Splenectomy During 52-Week Treatment Period [52 weeks]

   Occurrence of a splenectomy. Participants who discontinued study during the treatment period prior to reporting a splenectomy were considered as having had a splenectomy.

2. Number of Participants With Treatment Failure During 52-Week Treatment Period [52 weeks]

   Treatment failure was defined by platelet counts ≤ 20 x 10^9/L for 4 consecutive weeks at the highest recommended dose and schedule, a major bleeding event, or change in therapy due to an intolerable side effect or bleeding symptom.

Secondary Outcome Measures

1. Time to Splenectomy [52 weeks]

   Time to splenectomy in days calculated from date of randomization to date of splenectomy, or censored at date of end of treatment visit if no splenectomy was done during treatment period.

2. Percentage of Participants With Platelet Response [Weeks 1-8, and Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52]

   Platelet response was defined as platelet counts > 50 x 10^9/L, measured at each study visit (excluding those within 8 weeks of prior rescue medication use) up to the time of splenectomy or the end of initial treatment period, whichever occurred first.

3. Change in ITP-PAQ Physical Health Domain of Symptoms [Baseline and 52 weeks]

   Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of symptoms. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.

4. Change in ITP-PAQ Physical Health Domain of Fatigue [Baseline and 52 weeks]

   Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of fatigue. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.

5. Change in ITP-PAQ Physical Health Domain of Bother [Baseline and 52 weeks]

   Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of bother. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.

6. Change in ITP-PAQ Physical Health Domain of Activity [Baseline and 52 weeks]

   Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of activity. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is ≥ 18 years of age

• Subject has a diagnosis of Idiopathic Thrombocytopenia Purpura (ITP) according to the American Society of Hematology (ASH) guidelines

• If subject is > 60 years of age, subject has a written bone marrow biopsy report confirming the diagnosis of ITP

• Subject has received at least 1 prior therapy for ITP

• Subject has a platelet count < 50,000 or their platelet count falls to < 50,000 during or after a clinically-indicated taper or discontinuation of current ITP therapy

• Before any study-specific procedure, the appropriate written informed consent must be obtained

Exclusion Criteria:

• Subject has had a splenectomy for any reason

• Subject has an active malignancy

• Subject has a history of cancer, other than basal cell carcinoma or cervical carcinoma in situ, with treatment or active disease within 5 years

• Subject has a known history of bone marrow stem cell disorder

• Subject has participated in any study evaluating polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO), AMG 531, or a thrombopoietic protein

• Subject is receiving other investigational agents or procedures

• Subject is currently enrolled in, or has completed within the last 30 days, another investigational device or drug study

• Subject is pregnant or breast feeding

• Subject is not using adequate contraceptive precautions

• Subject has known sensitivity to any recombinant E. coli-derived product

• Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative

• Subject has any kind of disorder that compromises the ability of the subject to comply with study procedures

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Notice regarding posted summaries of trial results
• AmgenTrials clinical trials website

Publications

• Kuter DJ, Mathias SD, Rummel M, Mandanas R, Giagounidis AA, Wang X, Deuson RR. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol. 2012 May;87(5):558-61. doi: 10.1002/ajh.23163. Epub 2012 Mar 28.
• Kuter DJ, Rummel M, Boccia R, Macik BG, Pabinger I, Selleslag D, Rodeghiero F, Chong BH, Wang X, Berger DP. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med. 2010 Nov 11;363(20):1889-99. doi: 10.1056/NEJMoa1002625.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00415532
• Other Study ID Numbers: 20060131
• First Posted: Dec 25, 2006
• Last Update Posted: May 9, 2019
• Last Verified: May 1, 2019

• Keywords provided by Amgen: splenectomy; platelet; AMG 531; thrombopoietin; blood disorder; bleeding disorder; immune thrombocytopenic purpura; idiopathic thrombocytopenic purpura; immune (idiopathic) thrombocytopenic purpura; TPO; thrombopoietic protein
• Additional relevant MeSH terms: Thrombocytopenia; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Recruitment Details	First Subject Enrolled: 20-Dec-2006 Last Subject Enrolled: 01-Nov-2007

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Period Title: Treatment Period
STARTED	77	157
Received Treatment	75	154
Switched to Romiplostim Group	2	0
COMPLETED	60	142
NOT COMPLETED	17	15
Period Title: Treatment Period
STARTED	43	30
COMPLETED	34	18
NOT COMPLETED	9	12

Baseline Characteristics

Arm/Group Title	Standard of Care	Romiplostim	Total
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.	Total of all reporting groups
Overall Participants	77	157	234
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.7 (19.3)	54.8 (18.8)	54.7 (18.9)
Sex: Female, Male (Count of Participants)
Female	46 59.7%	85 54.1%	131 56%
Male	31 40.3%	72 45.9%	103 44%
Race/Ethnicity, Customized (Number) [Number]
White or Caucasian	69 89.6%	137 87.3%	206 88%
Black or African American	0 0%	6 3.8%	6 2.6%
Hispanic or Latino	5 6.5%	9 5.7%	14 6%
Asian (Chinese, Bangladeshi, Indian, Pakistani)	1 1.3%	5 3.2%	6 2.6%
American Indian or Alaska Native	1 1.3%	0 0%	1 0.4%
Other	1 1.3%	0 0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Splenectomy During 52-Week Treatment Period
Description	Occurrence of a splenectomy. Participants who discontinued study during the treatment period prior to reporting a splenectomy were considered as having had a splenectomy.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis set includes all randomized patients.

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Had splenectomy	28 36.4%	14 8.9%
Did not have splenectomy	49 63.6%	143 91.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Significant level is set at 0.05
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.172
	Confidence Interval	() 95%; 0.084 to 0.352
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants With Treatment Failure During 52-Week Treatment Period
Description	Treatment failure was defined by platelet counts ≤ 20 x 10^9/L for 4 consecutive weeks at the highest recommended dose and schedule, a major bleeding event, or change in therapy due to an intolerable side effect or bleeding symptom.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set. Participants who discontinued study during treatment period prior to experiencing treatment failure were considered as having had treatment failure.

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Had treatment failure	23 29.9%	18 11.5%
Did not have treatment failure	54 70.1%	139 88.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	Significant level is set at 0.05
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.307
	Confidence Interval	() 95%; 0.154 to 0.611
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to Splenectomy
Description	Time to splenectomy in days calculated from date of randomization to date of splenectomy, or censored at date of end of treatment visit if no splenectomy was done during treatment period.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Median (95% Confidence Interval) [days]	NA	NA

4. Secondary Outcome

Title	Percentage of Participants With Platelet Response
Description	Platelet response was defined as platelet counts > 50 x 10^9/L, measured at each study visit (excluding those within 8 weeks of prior rescue medication use) up to the time of splenectomy or the end of initial treatment period, whichever occurred first.
Time Frame	Weeks 1-8, and Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

Full analysis set. "N" indicates the number of participants with available data at each time point.

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Week 1 [N=75, 154]	6.7 8.7%	3.9 2.5%
Week 2 [N=71, 153]	28.2 36.6%	75.8 48.3%
Week 3 [N=70, 152]	34.3 44.5%	73.0 46.5%
Week 4 [N=170, 152]	30.0 39%	73.7 46.9%
Week 5 [N=68, 152]	32.4 42.1%	71.1 45.3%
Week 6 [N=66, 151]	30.3 39.4%	74.2 47.3%
Week 7 [N=66, 151]	30.3 39.4%	75.5 48.1%
Week 8 [N=65, 151]	29.2 37.9%	68.2 43.4%
Week 12 [N=62, 149]	25.8 33.5%	79.2 50.4%
Week 16 [N=61, 147]	34.4 44.7%	82.3 52.4%
Week 20 [N=58, 139]	36.2 47%	83.5 53.2%
Week 24 [N=58, 138]	31.0 40.3%	92.0 58.6%
Week 28 [N=57, 137]	40.4 52.5%	88.3 56.2%
Week 32 [N=55, 135]	34.5 44.8%	87.4 55.7%
Week 36 [N=54, 135]	33.3 43.2%	89.6 57.1%
Week 40 [N=52, 134]	38.5 50%	88.8 56.6%
Week 44 [N=51, 131]	51.0 66.2%	86.3 55%
Week 48 [N=48, 130]	41.7 54.2%	88.5 56.4%
Week 52 [N=38, 122]	50.0 64.9%	90.2 57.5%

5. Secondary Outcome

Title	Change in ITP-PAQ Physical Health Domain of Symptoms
Description	Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of symptoms. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Least Squares Mean (Standard Error) [Units on a scale]	12.5 (2.1)	16.0 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0133
	Comments	Significant level is set at 0.05
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Change in ITP-PAQ Physical Health Domain of Fatigue
Description	Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of fatigue. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set.

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Least Squares Mean (Standard Error) [Units on a scale]	9.5 (3.2)	11.2 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3434
	Comments	Significant level is set at 0.05
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Change in ITP-PAQ Physical Health Domain of Bother
Description	Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of bother. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Least Squares Mean (Standard Error) [Units on a scale]	13.0 (2.7)	16.8 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments	Significant level is set at 0.05
	Method	Mixed Models Analysis
	Comments

8. Secondary Outcome

Title	Change in ITP-PAQ Physical Health Domain of Activity
Description	Change from Baseline in the Immune Thrombocytopenic Purpura (ITP) Patient Assessment Questionnaire (PAQ) physical health domain of activity. This domain has a range of 0 to 100, with higher scores indicating a better health-related quality of life. Model included fixed effects of baseline assessment, geographic region, treatment group, assessment week, splenectomy status and treatment group-by-assessment week interaction. Treatment group and splenectomy status are time-varying covariates.
Time Frame	Baseline and 52 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Standard of Care	Romiplostim
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.	Romiplostim administered by subcutaneous injection once weekly at a starting dose of 3 μg/kg, adjusted to a maximum dose of 10 μg/kg to maintain a platelet count between 50 and 200 x 10^9/L for up to 52 weeks.
Measure Participants	77	157
Least Squares Mean (Standard Error) [Units on a scale]	8.2 (3.7)	17.1 (3.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard of Care, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0246
	Comments	Significant level is set at 0.05
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	52 week treatment period
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. 2 patients in Standard of Care (SOC) and 3 patients in the romiplostim arm did not receive the randomized treatment. 2 patients who were randomized to SOC and switched to romiplostim arm were counted in the Romiplostim arm.
Arm/Group Title	Standard of Care		AMG 531
Arm/Group Description	Medical standard of care treatments were selected and prescribed by the investigator according to standard institutional practices or therapeutic guidelines and administered for up to 52 weeks.
All Cause Mortality
	Standard of Care		AMG 531
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard of Care		AMG 531
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/73 (38.4%)		36/156 (23.1%)
Blood and lymphatic system disorders
Coagulopathy	1/73 (1.4%)		0/156 (0%)
Haemorrhagic diathesis	0/73 (0%)		1/156 (0.6%)
Idiopathic thrombocytopenic purpura	3/73 (4.1%)		0/156 (0%)
Thrombocytopenia	8/73 (11%)		6/156 (3.8%)
Cardiac disorders
Arrhythmia	1/73 (1.4%)		0/156 (0%)
Atrial fibrillation	1/73 (1.4%)		0/156 (0%)
Cardiac failure congestive	1/73 (1.4%)		0/156 (0%)
Cardio-respiratory arrest	1/73 (1.4%)		0/156 (0%)
Left ventricular failure	1/73 (1.4%)		0/156 (0%)
Myocardial infarction	0/73 (0%)		1/156 (0.6%)
Palpitations	0/73 (0%)		1/156 (0.6%)
Ventricular fibrillation	1/73 (1.4%)		0/156 (0%)
Eye disorders
Ocular vascular disorder	0/73 (0%)		1/156 (0.6%)
Gastrointestinal disorders
Abdominal pain	2/73 (2.7%)		1/156 (0.6%)
Abdominal pain upper	1/73 (1.4%)		0/156 (0%)
Dental caries	1/73 (1.4%)		0/156 (0%)
Gastrointestinal haemorrhage	1/73 (1.4%)		0/156 (0%)
Haematemesis	1/73 (1.4%)		0/156 (0%)
Nausea	0/73 (0%)		1/156 (0.6%)
Pancreatic fistula	1/73 (1.4%)		0/156 (0%)
Pancreatitis	1/73 (1.4%)		0/156 (0%)
Rectal haemorrhage	0/73 (0%)		1/156 (0.6%)
Small intestinal obstruction	0/73 (0%)		1/156 (0.6%)
Vomiting	0/73 (0%)		1/156 (0.6%)
General disorders
Asthenia	0/73 (0%)		1/156 (0.6%)
Face oedema	0/73 (0%)		1/156 (0.6%)
Oedema peripheral	0/73 (0%)		3/156 (1.9%)
Pyrexia	1/73 (1.4%)		1/156 (0.6%)
Hepatobiliary disorders
Cholecystitis	0/73 (0%)		1/156 (0.6%)
Hepatic failure	1/73 (1.4%)		0/156 (0%)
Hepatic function abnormal	0/73 (0%)		1/156 (0.6%)
Hepatitis toxic	0/73 (0%)		1/156 (0.6%)
Immune system disorders
Hypersensitivity	0/73 (0%)		1/156 (0.6%)
Infections and infestations
Appendicitis	0/73 (0%)		1/156 (0.6%)
Bacteraemia	1/73 (1.4%)		0/156 (0%)
Bronchitis	1/73 (1.4%)		0/156 (0%)
Cellulitis	0/73 (0%)		1/156 (0.6%)
Gastroenteritis norovirus	1/73 (1.4%)		0/156 (0%)
Herpes zoster	1/73 (1.4%)		0/156 (0%)
Klebsiella infection	0/73 (0%)		1/156 (0.6%)
Lobar pneumonia	0/73 (0%)		1/156 (0.6%)
Lower respiratory tract infection	0/73 (0%)		1/156 (0.6%)
Pneumonia	2/73 (2.7%)		4/156 (2.6%)
Sepsis	1/73 (1.4%)		0/156 (0%)
Subdiaphragmatic abscess	1/73 (1.4%)		0/156 (0%)
Tooth abscess	1/73 (1.4%)		0/156 (0%)
Urinary tract infection	1/73 (1.4%)		1/156 (0.6%)
Injury, poisoning and procedural complications
Contusion	0/73 (0%)		2/156 (1.3%)
Rib fracture	1/73 (1.4%)		0/156 (0%)
Spinal compression fracture	1/73 (1.4%)		0/156 (0%)
Wrist fracture	0/73 (0%)		1/156 (0.6%)
Investigations
Liver function test abnormal	1/73 (1.4%)		0/156 (0%)
Platelet count decreased	0/73 (0%)		1/156 (0.6%)
Metabolism and nutrition disorders
Hyperkalaemia	0/73 (0%)		1/156 (0.6%)
Malnutrition	1/73 (1.4%)		0/156 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/73 (0%)		2/156 (1.3%)
Back pain	0/73 (0%)		2/156 (1.3%)
Flank pain	1/73 (1.4%)		0/156 (0%)
Lumbar spinal stenosis	0/73 (0%)		1/156 (0.6%)
Mobility decreased	0/73 (0%)		1/156 (0.6%)
Muscular weakness	0/73 (0%)		1/156 (0.6%)
Musculoskeletal chest pain	0/73 (0%)		1/156 (0.6%)
Osteonecrosis	1/73 (1.4%)		2/156 (1.3%)
Pain in extremity	1/73 (1.4%)		2/156 (1.3%)
Polyarthritis	1/73 (1.4%)		0/156 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant	1/73 (1.4%)		0/156 (0%)
Neoplasm skin	0/73 (0%)		1/156 (0.6%)
Rectal cancer	1/73 (1.4%)		0/156 (0%)
Squamous cell carcinoma	0/73 (0%)		1/156 (0.6%)
Nervous system disorders
Depressed level of consciousness	1/73 (1.4%)		0/156 (0%)
Dizziness	0/73 (0%)		1/156 (0.6%)
Headache	1/73 (1.4%)		0/156 (0%)
Hepatic encephalopathy	1/73 (1.4%)		0/156 (0%)
Lethargy	0/73 (0%)		1/156 (0.6%)
Spinal haematoma	0/73 (0%)		1/156 (0.6%)
Syncope	0/73 (0%)		1/156 (0.6%)
Psychiatric disorders
Psychosomatic disease	1/73 (1.4%)		0/156 (0%)
Renal and urinary disorders
Renal colic	0/73 (0%)		1/156 (0.6%)
Renal failure	1/73 (1.4%)		1/156 (0.6%)
Renal failure acute	1/73 (1.4%)		0/156 (0%)
Renal impairment	1/73 (1.4%)		0/156 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/73 (1.4%)		1/156 (0.6%)
Epistaxis	0/73 (0%)		2/156 (1.3%)
Lung infiltration	1/73 (1.4%)		0/156 (0%)
Pleural effusion	0/73 (0%)		1/156 (0.6%)
Pulmonary embolism	0/73 (0%)		3/156 (1.9%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/73 (1.4%)		0/156 (0%)
Pruritus	0/73 (0%)		1/156 (0.6%)
Rash	0/73 (0%)		2/156 (1.3%)
Vascular disorders
Circulatory collapse	1/73 (1.4%)		0/156 (0%)
Deep vein thrombosis	0/73 (0%)		2/156 (1.3%)
Haemorrhage	0/73 (0%)		1/156 (0.6%)
Hypertensive crisis	1/73 (1.4%)		0/156 (0%)
Hypotension	0/73 (0%)		1/156 (0.6%)
Other (Not Including Serious) Adverse Events
	Standard of Care		AMG 531
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/73 (82.2%)		136/156 (87.2%)
Blood and lymphatic system disorders
Anaemia	4/73 (5.5%)		6/156 (3.8%)
Ear and labyrinth disorders
Vertigo	1/73 (1.4%)		9/156 (5.8%)
Gastrointestinal disorders
Abdominal pain	2/73 (2.7%)		8/156 (5.1%)
Abdominal pain upper	6/73 (8.2%)		4/156 (2.6%)
Constipation	6/73 (8.2%)		16/156 (10.3%)
Diarrhoea	4/73 (5.5%)		21/156 (13.5%)
Dyspepsia	4/73 (5.5%)		2/156 (1.3%)
Gingival bleeding	5/73 (6.8%)		9/156 (5.8%)
Nausea	6/73 (8.2%)		24/156 (15.4%)
Vomiting	2/73 (2.7%)		11/156 (7.1%)
General disorders
Chest pain	4/73 (5.5%)		6/156 (3.8%)
Fatigue	16/73 (21.9%)		43/156 (27.6%)
Influenza like illness	0/73 (0%)		8/156 (5.1%)
Oedema peripheral	3/73 (4.1%)		15/156 (9.6%)
Pain	2/73 (2.7%)		11/156 (7.1%)
Pyrexia	8/73 (11%)		15/156 (9.6%)
Immune system disorders
Hypersensitivity	4/73 (5.5%)		3/156 (1.9%)
Infections and infestations
Bronchitis	2/73 (2.7%)		9/156 (5.8%)
Gastroenteritis	1/73 (1.4%)		10/156 (6.4%)
Influenza	1/73 (1.4%)		13/156 (8.3%)
Nasopharyngitis	14/73 (19.2%)		36/156 (23.1%)
Sinusitis	1/73 (1.4%)		13/156 (8.3%)
Upper respiratory tract infection	6/73 (8.2%)		18/156 (11.5%)
Urinary tract infection	7/73 (9.6%)		18/156 (11.5%)
Injury, poisoning and procedural complications
Contusion	13/73 (17.8%)		22/156 (14.1%)
Procedural pain	5/73 (6.8%)		2/156 (1.3%)
Metabolism and nutrition disorders
Hypokalaemia	6/73 (8.2%)		2/156 (1.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/73 (5.5%)		23/156 (14.7%)
Back pain	4/73 (5.5%)		16/156 (10.3%)
Muscle spasms	4/73 (5.5%)		11/156 (7.1%)
Musculoskeletal pain	3/73 (4.1%)		14/156 (9%)
Myalgia	1/73 (1.4%)		17/156 (10.9%)
Neck pain	4/73 (5.5%)		1/156 (0.6%)
Pain in extremity	6/73 (8.2%)		20/156 (12.8%)
Nervous system disorders
Dizziness	6/73 (8.2%)		21/156 (13.5%)
Headache	14/73 (19.2%)		54/156 (34.6%)
Paraesthesia	0/73 (0%)		9/156 (5.8%)
Psychiatric disorders
Insomnia	9/73 (12.3%)		14/156 (9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/73 (5.5%)		25/156 (16%)
Dyspnoea	4/73 (5.5%)		15/156 (9.6%)
Epistaxis	17/73 (23.3%)		29/156 (18.6%)
Oropharyngeal pain	4/73 (5.5%)		19/156 (12.2%)
Skin and subcutaneous tissue disorders
Ecchymosis	4/73 (5.5%)		10/156 (6.4%)
Petechiae	13/73 (17.8%)		25/156 (16%)
Pruritus	5/73 (6.8%)		16/156 (10.3%)
Rash	5/73 (6.8%)		13/156 (8.3%)
Vascular disorders
Haematoma	9/73 (12.3%)		12/156 (7.7%)
Hypertension	4/73 (5.5%)		4/156 (2.6%)

Limitations/Caveats

[Not Specified]

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 multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.