E07-001: Safety and Efficacy Extension Study of Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01194804
• Collaborator: CMIC Co, Ltd. Japan (Industry)
• Enrollment: 27
• Arm: 1
• Duration (Months): 35

Study Details

Study Description

Brief Summary

The objective of this study was to assess the long-term safety and efficacy of eculizumab in hemolytic PNH patients who completed the 4-week screening and 12-week treatment period of the C07-001 study. In addition, pharmacokinetic and pharmacodynamic assessments of eculizumab were conducted.

Condition or Disease	Intervention/Treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria	Drug: Eculizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Study of Eculizumab (h5G1.1-mAb) in Hemolytic Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients: Extension Study to C07-001 Protocol
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eculizumab Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol	Drug: Eculizumab; Each vial contains 30 mL of 10 mg/mL eculizumab; dose of 900 mg intravenous every 14 days.; Other Names: Soliris

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Lactate Dehydrogenase [52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)]

Secondary Outcome Measures

1. Change From Baseline in FACIT-Fatigue Scale Total Score [52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)]

   The FACIT-Fatigue scale, Version 4.0, is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Patients score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.

2. Change From Baseline in PNH Red Blood Cell (RBC) Count [52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)]

3. Change From Baseline in Number of Units of Packed RBCs Transfused [52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)]

   Baseline is defined as the number of units transfused in 3 months prior to baseline

4. Change From Baseline in Plasma Free Hemoglobin [52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have fully completed C07-001 study 12-week treatment period

Exclusion Criteria:

• Patients who terminated early from the C07-001 study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alexion Pharmaceuticals
• CMIC Co, Ltd. Japan

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01194804
• Other Study ID Numbers: E07-001
• First Posted: Sep 3, 2010
• Last Update Posted: Sep 17, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion Pharmaceuticals: Hemolytic Paroxysmal Nocturnal Hemoglobinuria; Eculizumab; PNH
• Additional relevant MeSH terms: Hemoglobinuria; Hemoglobinuria, Paroxysmal; Eculizumab

Study Results

Participant Flow

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with paroxysmal nocturnal hemoglobinuria who have successfully completed the C07-001 protocol (NCT01192399) Eculizumab: 900 mg intravenous every 14 days.
Period Title: Overall Study
STARTED	27
COMPLETED	26
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (12.35)
Sex: Female, Male (Count of Participants)
Female	14 51.9%
Male	13 48.1%
Race/Ethnicity, Customized (Count of Participants)
Japanese	27 100%
Region of Enrollment (Count of Participants)
Japan	27 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Lactate Dehydrogenase
Time Frame	52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Measure Participants	26
Mean (Standard Error) [Units/Liter]	-15.9 (1.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eculizumab
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Sign test
	Comments

2. Secondary Outcome

Title	Change From Baseline in FACIT-Fatigue Scale Total Score
Description	The FACIT-Fatigue scale, Version 4.0, is a collection of quality of life questionnaires pertaining to the management of fatigue symptoms due to a chronic illness. The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days. Patients score each item on a 5-point scale: 0 (Not at all) to 4 (Very much). Total scores range from 0 to 52, with higher score indicating better quality of life.
Time Frame	52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Measure Participants	26
Mean (Standard Error) [units on a scale]	8.0 (1.95)

3. Secondary Outcome

Title	Change From Baseline in PNH Red Blood Cell (RBC) Count
Time Frame	52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Measure Participants	26
Mean (Standard Error) [cellsx10^12/L]	0.51 (0.129)

4. Secondary Outcome

Title	Change From Baseline in Number of Units of Packed RBCs Transfused
Description	Baseline is defined as the number of units transfused in 3 months prior to baseline
Time Frame	52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Measure Participants	26
Mean (Standard Error) [units]	-3.5 (1.43)

5. Secondary Outcome

Title	Change From Baseline in Plasma Free Hemoglobin
Time Frame	52 weeks (includes 12 weeks of eculizumab treatment in the parent study and 40 weeks in the extension study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
Measure Participants	26
Mean (Standard Error) [mg/dL]	-13.5 (8.55)

Adverse Events

Time Frame	From baseline (after first dose) to end of study (1 year).
Arm/Group Title	Eculizumab
Arm/Group Description	Treatment with eculizumab for patients with PNH who have successfully completed the C07-001 protocol 900 mg intravenous every 14 days.
All Cause Mortality
	Eculizumab
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	Eculizumab
	Affected / at Risk (%)	# Events
Total	12/27 (44.4%)
Blood and lymphatic system disorders
Anaemia	2/27 (7.4%)
Haemolysis	1/27 (3.7%)
Gastrointestinal disorders
Colitis	1/27 (3.7%)
General disorders
Pyrexia	2/27 (7.4%)
Hepatobiliary disorders
Cholelithiasis	1/27 (3.7%)
Jaundice cholestatic	1/27 (3.7%)
Infections and infestations
Pneumonia	4/27 (14.8%)
Bronchitis	1/27 (3.7%)
Cellulitis	1/27 (3.7%)
Gastroenteritis viral	1/27 (3.7%)
Herpes virus infection	1/27 (3.7%)
Sepsis	1/27 (3.7%)
Upper respiratory tract infection	1/27 (3.7%)
Injury, poisoning and procedural complications
Animal bite	1/27 (3.7%)
Subdural haematoma	1/27 (3.7%)
Renal and urinary disorders
Acute kidney injury	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Skin disorder	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	Eculizumab
	Affected / at Risk (%)	# Events
Total	26/27 (96.3%)
Blood and lymphatic system disorders
Anaemia	3/27 (11.1%)
Eye disorders
Conjunctival haemorrhage	3/27 (11.1%)
Cataract	2/27 (7.4%)
Gastrointestinal disorders
Diarrhoea	4/27 (14.8%)
Abdominal discomfort	2/27 (7.4%)
Dental caries	2/27 (7.4%)
Dyspepsia	2/27 (7.4%)
Enterocolitis	2/27 (7.4%)
Mouth ulceration	2/27 (7.4%)
General disorders
Pyrexia	4/27 (14.8%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/27 (7.4%)
Infections and infestations
Nasopharyngitis	21/27 (77.8%)
Upper respiratory tract infection	6/27 (22.2%)
Gastroenteritis	5/27 (18.5%)
Pharyngitis	3/27 (11.1%)
Injury, poisoning and procedural complications
Contusion	3/27 (11.1%)
Laceration	2/27 (7.4%)
Investigations
Blood alkaline phosphatase increased	6/27 (22.2%)
Blood bilirubin increased	2/27 (7.4%)
Metabolism and nutrition disorders
Diabetes mellitus	2/27 (7.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/27 (7.4%)
Back pain	2/27 (7.4%)
Nervous system disorders
Headache	6/27 (22.2%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	4/27 (14.8%)
Epistaxis	3/27 (11.1%)
Oropharyngeal pain	2/27 (7.4%)
Skin and subcutaneous tissue disorders
Rash	2/27 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.