P3 Study to Evaluate Efficacy and Safety of AMG 531 in Thrombocytopenic Japanese Subjects With Immune (Idiopathic) Thrombocytopenic Purpura

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00603642
• Collaborator: (none)
• Enrollment: 34
• Arms: 2
• Actual Duration (Months): 18.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of AMG 531 compared with placebo in thrombocytopenic Japanese subjects with immune (idiopathic) thrombocytopenic purpura (ITP) .

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Thrombocytopenic Purpura	Drug: Placebo; Drug: AMG 531	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo Controlled Phase 3 Study Evaluating the Efficacy and Safety of AMG 531 in Thrombocytopenic Japanese Subjects With Immune (Idiopathic) Thrombocytopenic Purpura
• Actual Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Apr 13, 2009
• Actual Study Completion Date: Apr 13, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: AMG 531 Double blinded placebo-controlled study	Drug: AMG 531; Subcutaneously administered, once a week, for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo; Subcutaneously administered, once a week, for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Weeks With Weekly Platelet Response [12 weeks (Weeks 2 - 13)]

   Number of weeks with weekly platelet response. A weekly platelet response is defined as a platelet count of ≥ 50 x 10^9/L on a weekly scheduled dose day from week 2 to week 13.

Secondary Outcome Measures

1. Increased Platelet Count From Baseline of at Least 20 x 10^9/L [Baseline, 12 weeks (Weeks 2 - 13)]

   An increase in platelet count of at least 20 x 10^9/L from baseline within the participant during the treatment period. Increase was calculated as the maximum observed platelet count during the treatment period minus the baseline platelet count.

2. Change From Baseline in Mean of Last 4 Weekly Platelet Counts [12 weeks (Weeks 2 - 13)]

   Change from baseline in the mean of the last 4 weekly platelet counts from week 2 to week 13.

3. Weeks With Platelet Count Between 50 and 200 [12 weeks (Weeks 2 - 13)]

   Number of weeks with platelet count between 50 x 10^9/L and 200 x 10^9/L inclusive during week 2 to week 13.

4. Rescue Medication(s) [12 weeks (Weeks 2 - 13)]

   Requirement for rescue medication(s) during treatment by the participant

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Japanese patients with diagnosis of ITP according to the diagnostic criteria proposed by Research Committee for Idiopathic Hematopoietic Disorders of the Ministry of Health, Labour and Welfare [MHLW] (revised in 1990) at least 6 months before the first screening visit

• The mean of the 3 scheduled platelet counts taken at the scheduled visits during the screening period must be ≤ 30 x 10^{9/L, with no individual count > 35 x 10}9/L

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Subjects must be ≥ 20 years of age at the time of obtaining the informed consent

• Have received at least 1 prior treatment for ITP

• If known Helicobacter pylori positive, having completed one course of Helicobacter pylori eradication therapy at least 12 weeks before the first screening visit

• A hemoglobin value taken at scheduled visit during the screening period must be ≥ 10 g/dL

• A serum creatinine concentration taken at scheduled visit during the screening period must be ≤ 2 mg/dL

• Adequate liver function, as evidenced by a total bilirubin taken at scheduled visit during the screening period ≤ 1.5 times of the upper limit of the normal range (except for patients with a confirmed diagnosis of Gilbert's Disease) or an alanine aminotransferase and aspartate aminotransferase taken at the screening visit ≤ 3 times of the upper limit of the normal range

Exclusion Criteria:

• Any known history of bone marrow stem cell disorder. Any abnormal bone marrow findings other than those typical of ITP.

• Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before the first screening visit.

• Documented diagnosis of arterial thrombosis (eg, stroke, transient ischemic attack, or myocardial infarction); history of venous thrombosis (eg, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy at the first screening visit.

• Documented diagnosis of anti phospholipid antibody syndrome

• Currently receiving any treatment for ITP except oral corticosteroids, azathioprine and/or danazol administered at a constant dose and schedule from at least 4 weeks prior to the first screening visit

• Received intravenous immunoglobulin, anti D immunoglobulin, or any drug administered to increase platelet counts (eg, immunosuppressants except azathioprine) within 2 weeks before the first screening visit

• Have had a splenectomy for any reason within 12 weeks before the first screening visit

• Past or present participation in any study evaluating pegacaristim (polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, KRN9000), Eltrombopag (SB 497115), recombinant human thrombopoietin, AMG 531, or other Mpl stimulation product

• Received hematopoietic growth factors (eg, granulocyte colony stimulating factor, macrophage colony stimulating factor, erythropoietin, interleukin 11) for any reason within 4 weeks before the first screening visit

• Received any anti malignancy agents (eg, cyclophosphamide, 6 mercaptopurine, vincristine, vinblastine, Interferon alfa) for any reason within 8 weeks before the first screening visit

• Received any monoclonal antibody drugs (eg, rituximab) for any reason within 14 weeks before the first screening visit

• Less than 4 weeks since receipt of any therapeutic drug or device that is not MHLW approved for any indication before the first screening visit

• Pregnant or breast feeding

• Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator

• Known severe drug hypersensitivity

• Concerns for subject's compliance with the protocol

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:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00603642
• Other Study ID Numbers: 20060216
• First Posted: Jan 29, 2008
• Last Update Posted: May 9, 2019
• Last Verified: May 1, 2019

• Keywords provided by Amgen: AMG 531; Idiopathic Thrombocytopenic Purpura; ITP; Thrombocytopenia; Japan; Placebo controlled; Phase 3
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 20 November 2007 through 11 December 2008

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Period Title: Overall Study
STARTED	12	22
COMPLETED	12	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Romiplostim	Total
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg	Total of all reporting groups
Overall Participants	12	22	34
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.6 (13.4)	58.5 (12.6)	54.7 (13.7)
Sex: Female, Male (Count of Participants)
Female	10 83.3%	14 63.6%	24 70.6%
Male	2 16.7%	8 36.4%	10 29.4%
Race/Ethnicity, Customized (Number) [Number]
Japanese	12 100%	22 100%	34 100%
Other	0 0%	0 0%	0 0%
Platelet Count (10^9/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^9/L]	15.8 (8.6)	18.4 (8.3)	17.5 (8.4)

Outcome Measures

1. Primary Outcome

Title	Weeks With Weekly Platelet Response
Description	Number of weeks with weekly platelet response. A weekly platelet response is defined as a platelet count of ≥ 50 x 10^9/L on a weekly scheduled dose day from week 2 to week 13.
Time Frame	12 weeks (Weeks 2 - 13)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Measure Participants	12	22
Median (Inter-Quartile Range) [Weeks]	0.0	11.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Increased Platelet Count From Baseline of at Least 20 x 10^9/L
Description	An increase in platelet count of at least 20 x 10^9/L from baseline within the participant during the treatment period. Increase was calculated as the maximum observed platelet count during the treatment period minus the baseline platelet count.
Time Frame	Baseline, 12 weeks (Weeks 2 - 13)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Measure Participants	12	22
Number [Participants]	3 25%	21 95.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change From Baseline in Mean of Last 4 Weekly Platelet Counts
Description	Change from baseline in the mean of the last 4 weekly platelet counts from week 2 to week 13.
Time Frame	12 weeks (Weeks 2 - 13)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Measure Participants	12	22
Mean (Standard Deviation) [10^9/L]	2.3 (6.5)	109.7 (88.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Weeks With Platelet Count Between 50 and 200
Description	Number of weeks with platelet count between 50 x 10^9/L and 200 x 10^9/L inclusive during week 2 to week 13.
Time Frame	12 weeks (Weeks 2 - 13)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Measure Participants	12	22
Mean (Standard Deviation) [Weeks]	0.2 (0.4)	6.3 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Rescue Medication(s)
Description	Requirement for rescue medication(s) during treatment by the participant
Time Frame	12 weeks (Weeks 2 - 13)

Outcome Measure Data

Analysis Population Description

Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo

Arm/Group Title	Placebo	Romiplostim
Arm/Group Description	Placebo administered subcutaneously once weekly for 12 weeks	Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg
Measure Participants	12	22
Number [Participants]	2 16.7%	2 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Romiplostim
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6015
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	12 weeks of treatment plus follow-up period up to 12 weeks
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Placebo		Romiplostim
Arm/Group Description
All Cause Mortality
	Placebo		Romiplostim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Romiplostim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		2/22 (9.1%)
Blood and lymphatic system disorders
Thrombocytopenia	0/12 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/12 (8.3%)		0/22 (0%)
Nervous system disorders
Cerebral haemorrhage	1/12 (8.3%)		0/22 (0%)
Subarachnoid haemorrhage	1/12 (8.3%)		1/22 (4.5%)
Other (Not Including Serious) Adverse Events
	Placebo		Romiplostim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		16/22 (72.7%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/12 (8.3%)		1/22 (4.5%)
Thrombocytopenia	0/12 (0%)		2/22 (9.1%)
Ear and labyrinth disorders
Tinnitus	1/12 (8.3%)		0/22 (0%)
Vertigo	1/12 (8.3%)		0/22 (0%)
Vertigo positional	1/12 (8.3%)		0/22 (0%)
Eye disorders
Eyelid function disorder	1/12 (8.3%)		0/22 (0%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)		1/22 (4.5%)
General disorders
Fatigue	0/12 (0%)		2/22 (9.1%)
Feeling abnormal	1/12 (8.3%)		0/22 (0%)
Malaise	2/12 (16.7%)		1/22 (4.5%)
Oedema peripheral	0/12 (0%)		4/22 (18.2%)
Hepatobiliary disorders
Gallbladder polyp	1/12 (8.3%)		0/22 (0%)
Infections and infestations
Bronchitis	1/12 (8.3%)		1/22 (4.5%)
Hordeolum	1/12 (8.3%)		0/22 (0%)
Nasopharyngitis	2/12 (16.7%)		9/22 (40.9%)
Pharyngitis	1/12 (8.3%)		0/22 (0%)
Skin infection	1/12 (8.3%)		0/22 (0%)
Injury, poisoning and procedural complications
Contusion	2/12 (16.7%)		0/22 (0%)
Thermal burn	0/12 (0%)		2/22 (9.1%)
Investigations
White blood cell count increased	1/12 (8.3%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)		2/22 (9.1%)
Arthritis	1/12 (8.3%)		0/22 (0%)
Back pain	0/12 (0%)		3/22 (13.6%)
Pain in extremity	0/12 (0%)		3/22 (13.6%)
Nervous system disorders
Headache	2/12 (16.7%)		7/22 (31.8%)
Hypoaesthesia	1/12 (8.3%)		0/22 (0%)
IIIrd nerve paralysis	1/12 (8.3%)		0/22 (0%)
Loss of consciousness	1/12 (8.3%)		0/22 (0%)
Psychiatric disorders
Depression	1/12 (8.3%)		0/22 (0%)
Renal and urinary disorders
Nephrocalcinosis	0/12 (0%)		2/22 (9.1%)
Reproductive system and breast disorders
Polymenorrhagia	1/12 (8.3%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional	1/12 (8.3%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Dry skin	1/12 (8.3%)		0/22 (0%)
Eczema	1/12 (8.3%)		1/22 (4.5%)
Petechiae	1/12 (8.3%)		1/22 (4.5%)
Urticaria	1/12 (8.3%)		1/22 (4.5%)

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.