Trial Outcomes & Findings for Eculizumab Pharmacokinetics/Pharmacodynamics Study in Pediatric/Adolescent Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT NCT00867932)

NCT ID: NCT00867932

Last Updated: 2018-10-31

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 7 participants
• Primary outcome timeframe: Pre-infusion and 1 hour post-infusion at End of Treatment (EOT) (Day 84 [Week 12]) or ET
• Results posted on: 2018-10-31

Participant Flow

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).

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.

Participant milestones

Measure	Eculizumab 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).
Overall Study STARTED	7
Overall Study Induction Phase	7
Overall Study Maintenance Phase	7
Overall Study Received at Least 1 Dose of Study Drug	7
Overall Study Intent-to-Treat (ITT) Population	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Eculizumab n=7 Participants 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.
Age, Continuous	15.01 years STANDARD_DEVIATION 2.28 • n=5 Participants
Age, Customized Children (2 to 11 years)	1 Participants n=5 Participants
Age, Customized Adolescents (12 to 17 years)	6 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-infusion and 1 hour post-infusion at End of Treatment (EOT) (Day 84 [Week 12]) or ET

Population: ITT Population: Participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Eculizumab n=7 Participants 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.
Peak And Trough Concentrations Of Eculizumab In Serum At Week 12 Trough concentration	192.5 μg/mL Interval 124.2 to 321.1
Peak And Trough Concentrations Of Eculizumab In Serum At Week 12 Peak concentration	425.4 μg/mL Interval 220.5 to 566.1

SECONDARY outcome

Timeframe: First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])

Population: ITT Population: Participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Eculizumab n=7 Participants 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.
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with at least 1 TEAE	7 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any serious TEAE	2 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any mild TEAE	4 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any moderate TEAE	1 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any severe TEAE	2 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any unrelated TEAE	2 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any possibly related TEAE	3 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any probably related TEAE	2 Participants
Number Of Participants With Treatment-emergent Adverse Events (TEAEs) Participants with any definitely related TEAE	0 Participants

SECONDARY outcome

Timeframe: Baseline, EOT (Day 84 [Week 12]) or ET

Population: ITT Population: Participants who received at least 1 dose of study drug.

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.

Outcome measures

Measure	Eculizumab n=7 Participants 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.
Area Under The Curve (AUC) Of The Change From Baseline To Week 12 In Levels Of Lactate Dehydrogenase (LDH)	-60634 Units * Days per Liter (U*Day/L) Standard Deviation 72916

SECONDARY outcome

Timeframe: Baseline, EOT (Day 84 [Week 12]) or ET

Population: ITT Population: Participants who received at least 1 dose of study drug.

Plasma-free hemoglobin was determined for each participant by using standard laboratory assays. The values of plasma-free hemoglobin were summarized by visit.

Outcome measures

Measure	Eculizumab n=7 Participants 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.
Concentration Of Plasma-free Hemoglobin At Baseline And Week 12 Baseline	17.70 mg per deciliter (mg/dL) Standard Deviation 19.091
Concentration Of Plasma-free Hemoglobin At Baseline And Week 12 Week 12	7.44 mg per deciliter (mg/dL) Standard Deviation 3.145

SECONDARY outcome

Timeframe: Baseline, Weeks 1 to 12 or ET

Population: ITT Population: Participants who received at least 1 dose of study drug.

Levels of LDH were determined by using standard laboratory assays. LDH values and the change of LDH from baseline were summarized by visit.

Outcome measures

Measure	Eculizumab n=7 Participants 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.
Change From Baseline In LDH Levels Baseline	1020 U/L Standard Deviation 967
Change From Baseline In LDH Levels Change from baseline at Week 1	-672 U/L Standard Deviation 837
Change From Baseline In LDH Levels Change from baseline at Week 2	-763 U/L Standard Deviation 916
Change From Baseline In LDH Levels Change from baseline at Week 3	-752 U/L Standard Deviation 934
Change From Baseline In LDH Levels Change from baseline at Week 4	-761 U/L Standard Deviation 924
Change From Baseline In LDH Levels Change from baseline at Week 8	-747 U/L Standard Deviation 904
Change From Baseline In LDH Levels Change from baseline at Week 12	-771 U/L Standard Deviation 914

Adverse Events

Eculizumab

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Eculizumab n=7 participants at risk 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.
Blood and lymphatic system disorders Anaemia	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Blood and lymphatic system disorders Aplastic anaemia	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Blood and lymphatic system disorders Thrombocytopenia	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Nervous system disorders Headache	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Reproductive system and breast disorders Menorrhagia	25.0% 1/4 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Reproductive system and breast disorders Vaginal haemorrhage	25.0% 1/4 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Infections and infestations Acute sinusitis	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Infections and infestations Catheter site cellulitis	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Infections and infestations Otitis media acute	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])

Other adverse events

Measure	Eculizumab n=7 participants at risk 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.
Blood and lymphatic system disorders Haemolysis	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Blood and lymphatic system disorders Lymph node pain	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Gastrointestinal disorders Abdominal pain upper	28.6% 2/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Gastrointestinal disorders Nausea	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
General disorders Fatigue	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
General disorders Pyrexia	28.6% 2/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Infections and infestations Upper respiratory tract infection	28.6% 2/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Injury, poisoning and procedural complications Contusion	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Investigations Blood glucose increased	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Metabolism and nutrition disorders Decreased appetite	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Nervous system disorders Headache	71.4% 5/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Renal and urinary disorders Chromaturia	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Reproductive system and breast disorders Vaginal discharge	25.0% 1/4 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Reproductive system and breast disorders Vulvovaginal pruritus	25.0% 1/4 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Respiratory, thoracic and mediastinal disorders Cough	28.6% 2/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Acne	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Petechiae	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Rash	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Rash papular	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Skin hyperpigmentation	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Skin and subcutaneous tissue disorders Swelling face	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])
Vascular disorders Hypotension	14.3% 1/7 • First dose of study drug (Day 0) to End of Follow-up (Week 20 [8 weeks after EOT])

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