Trial Outcomes & Findings for Safety and Efficacy Study of Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients (NCT NCT01192399)

NCT ID: NCT01192399

Last Updated: 2018-03-13

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2018-03-13

Participant Flow

Participant milestones

Measure	Eculizumab Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Overall Study STARTED	29
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Eculizumab Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Overall Study Lack of Efficacy	2

Baseline Characteristics

Safety and Efficacy Study of Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients

Baseline characteristics by cohort

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Age, Continuous	47.0 years STANDARD_DEVIATION 12.39 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race/Ethnicity, Customized Japanese	29 Participants n=5 Participants
Region of Enrollment Japan	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in Lactate Dehydrogenase Baseline	1845.1 Units/Liter Standard Error 115.34
Change From Baseline in Lactate Dehydrogenase Week 12	398.7 Units/Liter Standard Error 99.15
Change From Baseline in Lactate Dehydrogenase Change from Baseline at Week 12	-1446.4 Units/Liter Standard Error 138.68

SECONDARY outcome

Timeframe: Baseline, Week 12

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.

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score Baseline	38.5 units on a scale Standard Error 1.88
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Total Score Change from Baseline at Week 12	4.1 units on a scale Standard Error 2.25

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count Baseline	1.3 cells x 10^12/L Standard Error 0.14
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count Week 12	1.8 cells x 10^12/L Standard Error 0.19
Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Count Change from Baseline at Week 12	0.5 cells x 10^12/L Standard Error 0.10

SECONDARY outcome

Timeframe: 12 weeks pre-treatment, baseline, 12 weeks post-treatment

Comparison of number of units of pRBCs transfused in the 12 weeks prior to the first dose of eculizumab, and between baseline and 12 weeks after the first dose of eculizumab

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Number of Units of Packed Red Blood Cells (pRBCs) Transfused 12 Weeks Pre-Dose	5.2 Units Standard Error 1.04
Number of Units of Packed Red Blood Cells (pRBCs) Transfused 12 Weeks Post-Dose	1.5 Units Standard Error 0.67
Number of Units of Packed Red Blood Cells (pRBCs) Transfused Difference Post - Pre	-3.7 Units Standard Error 1.12

SECONDARY outcome

Timeframe: Baseline to Week 12

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in Lactate Dehydrogenase (LDH) Area Under the Curve (AUC)	-113540.5 U/L x Day Standard Error 10539.33

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Measure	Eculizumab n=29 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in Plasma Free Hemoglobin Baseline	22.6 mg/dL Standard Error 2.61
Change From Baseline in Plasma Free Hemoglobin Change from Baseline at Week 12	-19.8 mg/dL Standard Error 2.71

SECONDARY outcome

Timeframe: Baseline, Week 12

The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) incorporates 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. For global health status, a high score represents a high quality of life.

Outcome measures

Measure	Eculizumab n=28 Participants Eculizumab intravenous infusions every week x 4 doses, then 900 mg 1 week later for 1 dose, then 900 mg every 2 weeks for 4 doses
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score (Global Health Status)	8.9 units on a scale Standard Error 6.39

Adverse Events

Eculizumab

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Eculizumab n=29 participants at risk 600 mg of eculizumab as intravenous (IV) infusion once a week for 4 doses, followed by 900 mg eculizumab IV infusion 1 week later for 1 dose, then 900 mg eculizumab IV infusion every 2 weeks for 4 doses.
General disorders Pyrexia	3.4% 1/29 • Adverse events were collected over the full study period (12 weeks).
Investigations C-Reactive Protein Increased	3.4% 1/29 • Adverse events were collected over the full study period (12 weeks).

Other adverse events

Measure	Eculizumab n=29 participants at risk 600 mg of eculizumab as intravenous (IV) infusion once a week for 4 doses, followed by 900 mg eculizumab IV infusion 1 week later for 1 dose, then 900 mg eculizumab IV infusion every 2 weeks for 4 doses.
Blood and lymphatic system disorders Anaemia	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Blood and lymphatic system disorders Leukopenia	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Ear and labyrinth disorders Tinnitis	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Eye disorders Conjunctival haemorrhage	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Gastrointestinal disorders Nausea	20.7% 6/29 • Adverse events were collected over the full study period (12 weeks).
Gastrointestinal disorders Diarrhoea	13.8% 4/29 • Adverse events were collected over the full study period (12 weeks).
Gastrointestinal disorders Vomiting	10.3% 3/29 • Adverse events were collected over the full study period (12 weeks).
General disorders Chest discomfort	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
General disorders Fatigue	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
General disorders Pyrexia	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Infections and infestations Nasopharyngitis	41.4% 12/29 • Adverse events were collected over the full study period (12 weeks).
Investigations Blood alkaline phosphatase increased	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Investigations Blood bilirubin increased	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Nervous system disorders Headache	51.7% 15/29 • Adverse events were collected over the full study period (12 weeks).
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	6.9% 2/29 • Adverse events were collected over the full study period (12 weeks).
Skin and subcutaneous tissue disorders Eczema	10.3% 3/29 • Adverse events were collected over the full study period (12 weeks).

Additional Information

Alexion Pharmaceuticals, Inc

Alexion Pharmaceuticals, Inc

Email: clinicaltrials@alexion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place