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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03500549




Registration number
NCT03500549
Ethics application status
Date submitted
10/04/2018
Date registered
18/04/2018
Date last updated
25/03/2022

Titles & IDs
Public title
Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Scientific title
A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Secondary ID [1] 0 0
APL2-302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pegcetacoplan
Treatment: Drugs - Soliris

Experimental: Pegcetacoplan - 1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days.

Active comparator: Eculizumab - Complement (C5) Inhibitor.


Treatment: Drugs: Pegcetacoplan
Complement (C3) Inhibitor

Treatment: Drugs: Soliris
Complement (C5) Inhibitor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP
Timepoint [1] 0 0
Baseline and Week 16
Secondary outcome [1] 0 0
Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP
Timepoint [1] 0 0
Day 1 to Week 16
Secondary outcome [2] 0 0
LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP
Timepoint [2] 0 0
Baseline and Week 16
Secondary outcome [3] 0 0
LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP
Timepoint [3] 0 0
Baseline and Week 16
Secondary outcome [4] 0 0
LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP
Timepoint [4] 0 0
Baseline and Week 16
Secondary outcome [5] 0 0
Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16
Timepoint [5] 0 0
Baseline and Week 16
Secondary outcome [6] 0 0
Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16
Timepoint [6] 0 0
Week 16
Secondary outcome [7] 0 0
Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16
Timepoint [7] 0 0
Week 16
Secondary outcome [8] 0 0
LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP
Timepoint [8] 0 0
Baseline and Week 16
Secondary outcome [9] 0 0
LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP
Timepoint [9] 0 0
Baseline and Week 16
Secondary outcome [10] 0 0
LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP
Timepoint [10] 0 0
Baseline and Week 16
Secondary outcome [11] 0 0
LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP
Timepoint [11] 0 0
Baseline and Week 16
Secondary outcome [12] 0 0
Total Number of PRBC Units Transfused During the RCP
Timepoint [12] 0 0
Day 1 to Week 16
Secondary outcome [13] 0 0
Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period
Timepoint [13] 0 0
Baseline and Week 48
Secondary outcome [14] 0 0
Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period
Timepoint [14] 0 0
Week 17 and Week 48
Secondary outcome [15] 0 0
Mean Change From Baseline to Week 48 in ARC During the Treatment Period
Timepoint [15] 0 0
Baseline and Week 48
Secondary outcome [16] 0 0
Mean Change From Week 17 to Week 48 in ARC During the Open-label Period
Timepoint [16] 0 0
Week 17 and Week 48
Secondary outcome [17] 0 0
Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period
Timepoint [17] 0 0
Baseline and Week 48
Secondary outcome [18] 0 0
Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period
Timepoint [18] 0 0
Week 17 and Week 48
Secondary outcome [19] 0 0
Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period
Timepoint [19] 0 0
Baseline and Week 48
Secondary outcome [20] 0 0
Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period
Timepoint [20] 0 0
Week 17 and Week 48
Secondary outcome [21] 0 0
Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period
Timepoint [21] 0 0
Baseline and Week 48
Secondary outcome [22] 0 0
Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period
Timepoint [22] 0 0
Week 17 and Week 48
Secondary outcome [23] 0 0
Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period
Timepoint [23] 0 0
Baseline and Week 48
Secondary outcome [24] 0 0
Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period
Timepoint [24] 0 0
Week 17 and Week 48
Secondary outcome [25] 0 0
Total Number of PRBC Units Transfused During the Open-Label Period
Timepoint [25] 0 0
Week 17 to Week 48

Eligibility
Key inclusion criteria
* At least 18 years of age
* Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
* On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
* Hb <10.5 g/dL at the Screening Visit
* Absolute reticulocyte count > 1.0x ULN at the Screening Visit
* Platelet count of >50,000/mm3 at the Screening Visit
* Absolute neutrophil count >500/mm3 at the Screening Visit
* Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
* Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
* Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
* Willing and able to give informed consent
* Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
* Have a body mass index (BMI) =35.0 kg/m2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
* Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
* Hereditary complement deficiency
* History of bone marrow transplantation
* History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
* Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
* Currently breast-feeding women
* Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study

This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:

* History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
* Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
* QTcF > 470 ms, PR > 280 ms
* Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
* Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
* Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
* Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
Belgium
State/province [14] 0 0
Vlaams-Brabant
Country [15] 0 0
Belgium
State/province [15] 0 0
West-Vlaanderen
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
France
State/province [18] 0 0
Annecy
Country [19] 0 0
France
State/province [19] 0 0
Chalon-sur-Saône
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
France
State/province [23] 0 0
Pierre-Bénite
Country [24] 0 0
France
State/province [24] 0 0
Saint-Quentin
Country [25] 0 0
France
State/province [25] 0 0
Toulouse
Country [26] 0 0
Germany
State/province [26] 0 0
Baden-Württemberg
Country [27] 0 0
Germany
State/province [27] 0 0
North Rhine-Westphalia
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Japan
State/province [29] 0 0
Aichi
Country [30] 0 0
Japan
State/province [30] 0 0
Ibaraki
Country [31] 0 0
Japan
State/province [31] 0 0
Nagano
Country [32] 0 0
Japan
State/province [32] 0 0
Okayama
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Japan
State/province [34] 0 0
Wakayama
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Bucheon
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Daejeon
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Saint Petersburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Tyumen
Country [40] 0 0
Spain
State/province [40] 0 0
Las Palmas De Gran Canaria
Country [41] 0 0
Spain
State/province [41] 0 0
Valencia
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Apellis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.