Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT03500549 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: APL2-302
• Study Type: interventional
• Target: 80
• Locations: 11 countries
• Sites: 53

Brief Summary

Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Outcome Measures

Primary Outcomes (1)

• Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP

  Baseline was the average of measurements recorded before taking the first dose of pegcetacoplan, which included local and central laboratory values during the screening period. Analysis excluded data before the RCP and was censored for transfusions.

  Baseline and Week 16

Secondary Outcomes (25)

• Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP

  Day 1 to Week 16

• LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP

  Baseline and Week 16

• LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP

  Baseline and Week 16

• LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP

  Baseline and Week 16

• Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16

  Baseline and Week 16

Study Arms (2)

Pegcetacoplan

EXPERIMENTAL

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

Drug: Pegcetacoplan; Drug: Soliris

Eculizumab

ACTIVE COMPARATOR

Complement (C5) Inhibitor.

Drug: Pegcetacoplan; Drug: Soliris

Interventions

Pegcetacoplan DRUG

Complement (C3) Inhibitor

Also known as: APL-2

Eculizumab; Pegcetacoplan

Soliris DRUG

Complement (C5) Inhibitor

Eculizumab; Pegcetacoplan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (53)

University of Southern California

Los Angeles, California, 90033, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20057, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Lakes Research

Miami Lakes, Florida, 33014, United States

Location

Mid Florida Hematology and Oncology

Orange City, Florida, 32763, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Investigative Clinical Research of Indiana

Indianapolis, Indiana, 46260, United States

Location

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York Cancer & Blood Specialists

East Setauket, New York, 11733, United States

Location

New York Cancer & Blood Specialists

The Bronx, New York, 10469, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Good Samaritan Hospital

Corvallis, Oregon, 97330, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

HOPE Cancer Center of East Texas

Tyler, Texas, 75701, United States

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3000, Australia

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, Vlaams-Brabant, 1200, Belgium

Location

AZ Delta Campus Wilgenstraat

Roeselare, West-Vlaanderen, 8800, Belgium

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Toronto General Hospital

Toronto, Ontario, M9A1G2, Canada

Location

Centre Hospitalier Annecy Genevois

Annecy, 74374, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Centre Hospitalier Universitaire de Lille

Lille, 59037, France

Location

Institut Paoli-Calmettes Marseille

Marseille, 13009, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier de Saint-Quentin

Saint-Quentin, 02321, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, Aichi-ken, 453-8511, Japan

Location

Japanese Red Cross Nagoya Daini Hospital

Showa-ku, Aichi-ken, 453-8650, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Shinshu University Hospital

Matsumoto, Nagano, 390-8621, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8421, Japan

Location

NTT Medical Center Tokyo

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Kinan Hospital

Tanabe, Wakayama, 646-8588, Japan

Location

Pavlov First Saint Petersburg State Medical University of Russian Ministry of Health

Saint Petersburg, 197022, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

Institution of Health Care of Tyumen Region

Tyumen, 625023, Russia

Location

Soonchunhyang University Bucheon Hospital

Bucheon-si, 14584, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital Universitario Politécnico La Fe

Valencia, 46026, Spain

Location

St. James' Institute of Oncology, Leeds Teaching Hospitals

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (11)

• 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.

  PMID: 40720060 DERIVED

• 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.

  PMID: 40285403 DERIVED

• 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.

  PMID: 39079163 DERIVED

• 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.

  PMID: 38727860 DERIVED

• 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.

  PMID: 38593241 DERIVED

• 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.

  PMID: 37707673 DERIVED

• 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.

  PMID: 36055332 DERIVED

• 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.

  PMID: 35869984 DERIVED

• 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.

  PMID: 35796199 DERIVED

• 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.

  PMID: 34445916 DERIVED

• 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.

  PMID: 33730455 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

pegcetacoplan; eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: April 18, 2018
• Study Start: June 14, 2018
• Primary Completion: November 14, 2019
• Study Completion: August 13, 2020
• Last Updated: March 25, 2022
• Results First Posted: March 25, 2022

Record last verified: 2022-03

Locations

US (19); DE (4); GB (1); FR (8); BE (2); KR (3); RU (3); JP (8); AU (1); ES (2); CA (2)