Trial Outcomes & Findings for Extension Study of Eculizumab in Patients With Transfusion Dependent Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT NCT00122317)
NCT ID: NCT00122317
Last Updated: 2018-03-13
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
187 participants
Primary outcome timeframe
From time of consent to a maximum of 2.5 years of study treatment
Results posted on
2018-03-13
Participant Flow
Participant milestones
| Measure |
Eculizumab
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Overall Study
STARTED
|
187
|
|
Overall Study
COMPLETED
|
176
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Eculizumab
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Overall Study
Death
|
3
|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
patient non-compliance
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Extension Study of Eculizumab in Patients With Transfusion Dependent Paroxysmal Nocturnal Hemoglobinuria (PNH)
Baseline characteristics by cohort
| Measure |
Eculizumab
n=187 Participants
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Age, Continuous
|
42.1 years
STANDARD_DEVIATION 14.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
101 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
6 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
168 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From time of consent to a maximum of 2.5 years of study treatmentOutcome measures
| Measure |
Eculizumab
n=187 Participants
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Incidence of Treatment-emergent Adverse Events
|
182 Participants
|
SECONDARY outcome
Timeframe: From time of first infusion through 24 months of study treatmentOutcome measures
| Measure |
Eculizumab
n=184 Participants
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Hemolysis as Measured by Change From Baseline in LDH Area Under the Curve
|
-365185.8 U/L x Day
Standard Deviation 210407.1
|
SECONDARY outcome
Timeframe: From time of first infusion through 24 months of study treatmentThe FACIT-Fatigue scale 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=184 Participants
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Quality of Life as Measured by FACIT-Fatigue Scale Change From Baseline
|
9.24 units on a scale
Standard Deviation 12.42
|
SECONDARY outcome
Timeframe: From time of first ever dose through last dose (up to 24 months of study treatment)Thrombosis was defined as occurrence of major adverse vascular events
Outcome measures
| Measure |
Eculizumab
n=184 Participants
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Incidence of Thrombosis After Eculizumab Infusion
Prior to first eculizumab dose
|
7.82 Number of events per 100 patient-years
|
|
Incidence of Thrombosis After Eculizumab Infusion
From first dose of eculizumab through last dose
|
1.99 Number of events per 100 patient-years
|
Adverse Events
Eculizumab
Serious events: 57 serious events
Other events: 180 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Eculizumab
n=187 participants at risk
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Blood and lymphatic system disorders
Anaemia
|
1.6%
3/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Blood and lymphatic system disorders
Aplastic anaemia
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Blood and lymphatic system disorders
Haemolysis
|
2.7%
5/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Renal and urinary disorders
Paroxysmal Nocturnal Haemoglobinuria
|
2.1%
4/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Cardiac disorders
Cardiac Failure
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Eye disorders
Retinal vein thrombosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
2.7%
5/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Ascites
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Colitis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Sigmoiditis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Chest pain
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Pyrexia
|
2.7%
5/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Bile duct stone
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Cholecystitis
|
1.6%
3/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Hepatic vein thrombosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Bacterial sepsis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Bronchitis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Cellulitis
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Cellulitis gangrenous
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Empyema
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Immune system disorders
Endocarditis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Enterococcal sepsis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Gallbladder abscess
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Gastroenteritis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Gastroenteritis viral
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Haemophilus infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Liver abscess
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Lower respiratory tract infection
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Meningococcal sepsis
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Necrotising fasciitis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Penile infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Pneumonia
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Respiratory tract infection
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Sepsis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Septic shock
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Staphylococcal Infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Urinary Tract Infection
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Viral Infection
|
1.6%
3/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Injury, poisoning and procedural complications
Drug Toxicity
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Injury, poisoning and procedural complications
Wrist Fracture
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Investigations
Haemoglobin Decreased
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Tenosynovitis Stenosans
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic Myelomonocytic Leukaemia
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Bone
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Convulsion
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Headache
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Metabolic Encephalopathy
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Psychiatric disorders
Suicidal Ideation
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Renal and urinary disorders
Calculus Urinary
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Renal and urinary disorders
Renal Failure Acute
|
1.1%
2/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Renal and urinary disorders
Renal Impairment
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Reproductive system and breast disorders
Erectile Dysfunction
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Reproductive system and breast disorders
Ovarian Cyst Ruptured
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Vascular disorders
Hypotension
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Vascular disorders
Phlebothrombosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Vascular disorders
Thrombophlebitis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Vascular disorders
Thrombosis
|
0.53%
1/187 • From time of consent to a maximum of 2.5 years of study treatment
|
Other adverse events
| Measure |
Eculizumab
n=187 participants at risk
eculizumab: 600 mg intravenous infusion every week x 4 then 900 mg iv every two weeks
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
23.5%
44/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Nausea
|
20.9%
39/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Vomiting
|
20.3%
38/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Abdominal Pain
|
13.4%
25/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
9.6%
18/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Constipation
|
8.6%
16/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
7.5%
14/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Influenza like Illness
|
15.5%
29/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Pyrexia
|
9.6%
18/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Oedema Peripheral
|
6.4%
12/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Fatigue
|
5.9%
11/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
General disorders
Chest Pain
|
5.3%
10/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Nasopharyngitis
|
39.6%
74/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
31.0%
58/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Urinary Tract Infection
|
10.7%
20/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Viral Infection
|
9.1%
17/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Sinusitis
|
8.0%
15/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Gastroenteritis
|
6.4%
12/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Herpes Simplex
|
6.4%
12/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Bronchitis
|
5.3%
10/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Infections and infestations
Influenza
|
5.3%
10/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Injury, poisoning and procedural complications
Contusion
|
11.8%
22/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.6%
33/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
17.1%
32/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
13.4%
25/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
17/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle Cramp
|
5.3%
10/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Headache
|
32.6%
61/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Nervous system disorders
Dizziness
|
11.2%
21/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Psychiatric disorders
Insomnia
|
5.9%
11/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.5%
29/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
13.4%
25/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.5%
14/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.4%
12/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
11/187 • From time of consent to a maximum of 2.5 years of study treatment
|
|
Vascular disorders
Haematoma
|
6.4%
12/187 • From time of consent to a maximum of 2.5 years of study treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Participation in this multicenter study involved a commitment to publish the data from the study in a cooperative publication prior to release of study results on an individual basis.
- Publication restrictions are in place
Restriction type: OTHER