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Eculizumab Pharmacokinetics/Pharmacodynamics Study in Pediatric/Adolescent Paroxysmal Nocturnal Hemoglobinuria (PNH)

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ClinicalTrials.gov Identifier: NCT00867932
Recruitment Status : Completed
First Posted : March 24, 2009
Results First Posted : October 31, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hemoglobinuria, Paroxysmal
Intervention Drug: Eculizumab
Enrollment 7
Recruitment Details The recruitment period lasted from October 2009 to January 2011. Three sites in the United States of America enrolled a total of 7 participants with paroxysmal nocturnal hemoglobinuria (PNH).
Pre-assignment Details Participants who completed this study could have continued treatment with commercially available eculizumab (Soliris®) and been followed in the Soliris® PNH Registry. Those who didn't complete the study or who didn't continue with Soliris® treatment after the study were followed for 8 weeks and monitored for signs and symptoms of serious hemolysis.
Arm/Group Title Eculizumab
Hide Arm/Group Description Eculizumab was administered as an intravenous (IV) infusion for 12 weeks. All participants weighed more than 45 kilograms (kg) and received the following weight-based dosing regimen: induction/loading = 600 milligram (mg) weekly x 4; maintenance = 900 mg at Week (Wk) 5; 900 mg every 2 weeks (Q2W).
Period Title: Overall Study
Started 7
Induction Phase 7
Maintenance Phase 7
Received at Least 1 Dose of Study Drug 7
Intent-to-Treat (ITT) Population [1] 7
Completed 7
Not Completed 0
[1]
Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Baseline Participants 7
Hide Baseline Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants
15.01  (2.28)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
Children (2 to 11 years)
1
  14.3%
Adolescents (12 to 17 years)
6
  85.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants
Female
4
  57.1%
Male
3
  42.9%
1.Primary Outcome
Title Peak And Trough Concentrations Of Eculizumab In Serum At Week 12
Hide Description Serum concentrations of eculizumab were measured by using a validated enzyme-linked immunosorbent assay (ELISA) method developed at Alexion Pharmaceuticals Bioanalytical Laboratory. The range of the analytical assay was 10 to 600 microgram per milliliter (μg/mL). Peak concentrations were not measured at the early termination (ET) visit.
Time Frame Pre-infusion and 1 hour post-infusion at End of Treatment (EOT) (Day 84 [Week 12]) or ET
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description:
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: μg/mL
Trough concentration
192.5
(124.2 to 321.1)
Peak concentration
425.4
(220.5 to 566.1)
2.Secondary Outcome
Title Number Of Participants With Treatment-emergent Adverse Events (TEAEs)
Hide Description A TEAE was defined as any adverse event (AE) not present prior to exposure to eculizumab or any event already present that worsened in either intensity or frequency following exposure to eculizumab. A serious TEAE was defined as any event that resulted in death, was immediately life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. Related TEAEs were considered by investigators to be definitely, probably, or possibly related to administration of the study drug. Relationship is ordered as follows: unrelated, possibly related, probably related, or definitely related. TEAEs and TEAE severity were classified in accordance with the Medical Dictionary for Regulatory Activities (MedDRA) 13.0 dictionary. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description:
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Participants Analyzed 7
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at least 1 TEAE
7
 100.0%
Participants with any serious TEAE
2
  28.6%
Participants with any mild TEAE
4
  57.1%
Participants with any moderate TEAE
1
  14.3%
Participants with any severe TEAE
2
  28.6%
Participants with any unrelated TEAE
2
  28.6%
Participants with any possibly related TEAE
3
  42.9%
Participants with any probably related TEAE
2
  28.6%
Participants with any definitely related TEAE
0
   0.0%
3.Secondary Outcome
Title Area Under The Curve (AUC) Of The Change From Baseline To Week 12 In Levels Of Lactate Dehydrogenase (LDH)
Hide Description The AUC of LDH was calculated by using the change of LDH from baseline values for each participant up to Week 12. For those participants with missing LDH values, the last observation carried forward method (LOCF) was used to impute missing values. Individual AUC values of LDH were summarized and tabulated.
Time Frame Baseline, EOT (Day 84 [Week 12]) or ET
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description:
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: Units * Days per Liter (U*Day/L)
-60634  (72916)
4.Secondary Outcome
Title Concentration Of Plasma-free Hemoglobin At Baseline And Week 12
Hide Description Plasma-free hemoglobin was determined for each participant by using standard laboratory assays. The values of plasma-free hemoglobin were summarized by visit.
Time Frame Baseline, EOT (Day 84 [Week 12]) or ET
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description:
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mg per deciliter (mg/dL)
Baseline 17.70  (19.091)
Week 12 7.44  (3.145)
5.Secondary Outcome
Title Change From Baseline In LDH Levels
Hide Description Levels of LDH were determined by using standard laboratory assays. LDH values and the change of LDH from baseline were summarized by visit.
Time Frame Baseline, Weeks 1 to 12 or ET
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: Participants who received at least 1 dose of study drug.
Arm/Group Title Eculizumab
Hide Arm/Group Description:
Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: U/L
Baseline 1020  (967)
Change from baseline at Week 1 -672  (837)
Change from baseline at Week 2 -763  (916)
Change from baseline at Week 3 -752  (934)
Change from baseline at Week 4 -761  (924)
Change from baseline at Week 8 -747  (904)
Change from baseline at Week 12 -771  (914)
Time Frame First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Eculizumab
Hide Arm/Group Description Eculizumab was administered as an IV infusion for 12 weeks. All participants weighed more than 45 kg and received the following weight-based dosing regimen: induction/loading = 600 mg weekly x 4; maintenance = 900 mg at Wk 5; 900 mg Q2W.
All-Cause Mortality
Eculizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Eculizumab
Affected / at Risk (%)
Total   2/7 (28.57%) 
Blood and lymphatic system disorders   
Anaemia  1  1/7 (14.29%) 
Aplastic anaemia  1  1/7 (14.29%) 
Thrombocytopenia  1  1/7 (14.29%) 
Infections and infestations   
Acute sinusitis  1  1/7 (14.29%) 
Catheter site cellulitis  1  1/7 (14.29%) 
Otitis media acute  1  1/7 (14.29%) 
Nervous system disorders   
Headache  1  1/7 (14.29%) 
Reproductive system and breast disorders   
Menorrhagia  1 [1]  1/4 (25.00%) 
Vaginal haemorrhage  1 [1]  1/4 (25.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
[1]
Includes only female participants.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Eculizumab
Affected / at Risk (%)
Total   7/7 (100.00%) 
Blood and lymphatic system disorders   
Haemolysis  1  1/7 (14.29%) 
Lymph node pain  1  1/7 (14.29%) 
Gastrointestinal disorders   
Abdominal pain upper  1  2/7 (28.57%) 
Diarrhoea  1  1/7 (14.29%) 
Nausea  1  1/7 (14.29%) 
General disorders   
Fatigue  1  1/7 (14.29%) 
Pyrexia  1  2/7 (28.57%) 
Infections and infestations   
Upper respiratory tract infection  1  2/7 (28.57%) 
Injury, poisoning and procedural complications   
Contusion  1  1/7 (14.29%) 
Investigations   
Blood glucose increased  1  1/7 (14.29%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/7 (14.29%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/7 (14.29%) 
Nervous system disorders   
Headache  1  5/7 (71.43%) 
Renal and urinary disorders   
Chromaturia  1  1/7 (14.29%) 
Reproductive system and breast disorders   
Vaginal discharge  1 [1]  1/4 (25.00%) 
Vulvovaginal pruritus  1 [1]  1/4 (25.00%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/7 (28.57%) 
Nasal congestion  1  1/7 (14.29%) 
Rhinorrhoea  1  1/7 (14.29%) 
Skin and subcutaneous tissue disorders   
Acne  1  1/7 (14.29%) 
Petechiae  1  1/7 (14.29%) 
Rash  1  1/7 (14.29%) 
Rash papular  1  1/7 (14.29%) 
Skin hyperpigmentation  1  1/7 (14.29%) 
Swelling face  1  1/7 (14.29%) 
Vascular disorders   
Hypotension  1  1/7 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
[1]
Includes only female participants.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alexion Pharmaceuticals Inc.
Organization: Alexion Pharmaceuticals Inc.
EMail: ClinicalTrials@Alexion.com
Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00867932     History of Changes
Other Study ID Numbers: M07-005
2009-010402-11 ( EudraCT Number )
First Submitted: March 23, 2009
First Posted: March 24, 2009
Results First Submitted: October 3, 2018
Results First Posted: October 31, 2018
Last Update Posted: October 31, 2018