Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
NCT ID: NCT03500549
Last Updated: 2022-03-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
80 participants
INTERVENTIONAL
2018-06-14
2020-08-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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Pegcetacoplan
1080 mg pegcetacoplan administered subcutaneously twice-weekly or every three days.
Pegcetacoplan
Complement (C3) Inhibitor
Soliris
Complement (C5) Inhibitor
Eculizumab
Complement (C5) Inhibitor.
Pegcetacoplan
Complement (C3) Inhibitor
Soliris
Complement (C5) Inhibitor
Interventions
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Pegcetacoplan
Complement (C3) Inhibitor
Soliris
Complement (C5) Inhibitor
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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)
18 Years
ALL
No
Sponsors
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Apellis Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Locations
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Samsung Medical Center
Seoul, , South Korea
Soonchunhyang University Bucheon Hospital
Bucheon-si, , South Korea
Chungnam National University Hospital
Daejeon, , South Korea
University of Southern California
Los Angeles, California, United States
Sarcoma Oncology Research Center
Santa Monica, California, United States
Denver Health
Denver, Colorado, United States
Georgetown University Hospital
Washington D.C., District of Columbia, United States
Cancer Specialists of North Florida
Jacksonville, Florida, United States
Lakes Research
Miami Lakes, Florida, United States
Mid Florida Hematology and Oncology
Orange City, Florida, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
Investigative Clinical Research of Indiana
Indianapolis, Indiana, United States
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
New York Cancer & Blood Specialists
East Setauket, New York, United States
New York Cancer & Blood Specialists
The Bronx, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Good Samaritan Hospital
Corvallis, Oregon, United States
University of Tennessee Medical Center
Knoxville, Tennessee, United States
Baptist Cancer Center
Memphis, Tennessee, United States
HOPE Cancer Center of East Texas
Tyler, Texas, United States
Royal Melbourne Hospital
Melbourne, Victoria, Australia
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Vlaams-Brabant, Belgium
AZ Delta Campus Wilgenstraat
Roeselare, West-Vlaanderen, Belgium
University of Alberta
Edmonton, Alberta, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Centre Hospitalier Annecy Genevois
Annecy, , France
Centre Hospitalier William Morey
Chalon-sur-Saône, , France
Centre Hospitalier Universitaire de Lille
Lille, , France
Institut Paoli-Calmettes Marseille
Marseille, , France
Hôpital Saint-Louis
Paris, , France
Centre Hospitalier Lyon Sud
Pierre-Bénite, , France
Centre Hospitalier de Saint-Quentin
Saint-Quentin, , France
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse, , France
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
Uniklinik RWTH Aachen
Aachen, North Rhine-Westphalia, Germany
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Universitätsklinikum Hamburg Eppendorf
Hamburg, , Germany
Japanese Red Cross Nagoya Daiichi Hospital
Nagoya, Aichi-ken, Japan
Japanese Red Cross Nagoya Daini Hospital
Showa-ku, Aichi-ken, Japan
University of Tsukuba Hospital
Tsukuba, Ibaraki, Japan
Shinshu University Hospital
Matsumoto, Nagano, Japan
Okayama University Hospital
Okayama, Okayama-ken, Japan
Juntendo University Hospital
Bunkyo-ku, Tokyo, Japan
NTT Medical Center Tokyo
Shinagawa-ku, Tokyo, Japan
Kinan Hospital
Tanabe, Wakayama, Japan
Pavlov First Saint Petersburg State Medical University of Russian Ministry of Health
Saint Petersburg, , Russia
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, , Russia
Institution of Health Care of Tyumen Region
Tyumen, , Russia
Hospital Universitario de Gran Canaria Dr. Negrín
Las Palmas de Gran Canaria, , Spain
Hospital Universitario Politécnico La Fe
Valencia, , Spain
St. James' Institute of Oncology, Leeds Teaching Hospitals
Leeds, , United Kingdom
Countries
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References
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de Castro C, Kelly RJ, Griffin M, Patriquin CJ, Mulherin B, Hochsmann B, Selvaratnam V, Wong RSM, Hillmen P, Horneff R, Uchendu UO, Zhang Y, Surova E, Szamosi J, de Latour RP. Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan. Adv Ther. 2025 Sep;42(9):4641-4658. doi: 10.1007/s12325-025-03310-8. Epub 2025 Jul 28.
de Latour RP, Kulasekararaj A, Dingli D, Wilson K, Wojciechowski P, Hakimi Z, Nazir J, Czech B, Hillmen P, Szer J. Anchored Indirect Treatment Comparison Finds Comparable Effects of Pegcetacoplan and Iptacopan in Paroxysmal Nocturnal Haemoglobinuria. Eur J Haematol. 2025 Aug;115(2):125-133. doi: 10.1111/ejh.14422. Epub 2025 Apr 25.
Panse J, Daguindau N, Okuyama S, Peffault de Latour R, Schafhausen P, Straetmans N, Al-Adhami M, Persson E, Wong RSM. Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin >/=10 g/dL) who had received eculizumab or were naive to complement inhibitors. PLoS One. 2024 Jul 29;19(7):e0306407. doi: 10.1371/journal.pone.0306407. eCollection 2024.
Mulherin BP, Yeh M, Al-Adhami M, Dingli D. Normalization of Hemoglobin, Lactate Dehydrogenase, and Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Pegcetacoplan. Drugs R D. 2024 Jun;24(2):169-177. doi: 10.1007/s40268-024-00463-9. Epub 2024 May 10.
Peffault de Latour R, Griffin M, Kelly RJ, Szer J, de Castro C, Horneff R, Tan L, Yeh M, Panse J. Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2024 Jun 11;8(11):2718-2725. doi: 10.1182/bloodadvances.2024012672.
Sharma V, Koprivnikar J, Drago K, Savage J, Bachelor A. Injection Site Reactions with Long-Term Pegcetacoplan Use in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Brief Report. Adv Ther. 2023 Nov;40(11):5115-5129. doi: 10.1007/s12325-023-02653-4. Epub 2023 Sep 14.
de Latour RP, Szer J, Weitz IC, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro CM, Nishimori H, Ajayi T, Al-Adhami M, Deschatelets P, Francois C, Grossi F, Risitano AM, Hillmen P. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022 Sep;9(9):e648-e659. doi: 10.1016/S2352-3026(22)00210-1.
Cella D, Sarda SP, Hsieh R, Fishman J, Hakimi Z, Hoffman K, Al-Adhami M, Nazir J, Cutts K, Lenderking WR. Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study. Ann Hematol. 2022 Sep;101(9):1905-1914. doi: 10.1007/s00277-022-04887-8. Epub 2022 Jul 23.
Hakimi Z, Wilson K, McAughey E, Pochopien M, Wojciechowski P, Toumi M, Knight C, Sarda SP, Patel N, Wiseman C, de Castro NP, Nazir J, Kelly RJ. The cost-effectiveness, of pegcetacoplan compared with ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria, in a UK setting. J Comp Eff Res. 2022 Sep;11(13):969-985. doi: 10.2217/cer-2022-0076. Epub 2022 Jul 7.
Bhak RH, Mody-Patel N, Baver SB, Kunzweiler C, Yee CW, Sundaresan S, Swartz N, Duh MS, Krishnan S, Sarda SP. Comparative effectiveness of pegcetacoplan versus ravulizumab in patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a matching-adjusted indirect comparison. Curr Med Res Opin. 2021 Nov;37(11):1913-1923. doi: 10.1080/03007995.2021.1971182. Epub 2021 Sep 3.
Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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APL2-302
Identifier Type: -
Identifier Source: org_study_id
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