A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH

NCT04085601 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: APL2-308
• Study Type: interventional
• Target: 53
• Locations: 10 countries
• Sites: 30

Brief Summary

Evaluation of the Efficacy and Safety of Pegcetacoplan in Patients with Paroxysmal Nocturnal Hemoglobinuria .

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Outcome Measures

Primary Outcomes (2)

• Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization

  The Hb stabilization was defined as avoidance of a \>1 gram per deciliter (g/dL) decrease in Hb concentration from Baseline in the absence of transfusion through Week 26.

  From Baseline (Day 1) up to Week 26

• Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26

  The LDH concentration was analyzed using an analysis of covariance (ANCOVA) model with a last observation carried forward (LOCF) and a baseline observation carried forward (BOCF) approach for handling missing data. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

  Baseline (Day 1) and Week 26

Secondary Outcomes (14)

• Number of Subjects With an Hb Response in the Absence of Transfusions

  Baseline and Week 26

• Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26

  Baseline and Week 26

• Change From Baseline in Hb Concentration at Week 26

  Baseline and Week 26

• Percentage of Subjects Who Received Transfusion or Decrease of Hb >2 g/dL From Baseline

  At Week 26

• Percentage of Subjects With Transfusion Avoidance

  At Week 26

Study Arms (2)

Standard of Care (SOC) excluding complement inhibitors

NO INTERVENTION

1,080mg APL-2 administered subcutaneously twice weekly

EXPERIMENTAL

Drug: APL-2

Interventions

APL-2 DRUG

Complement (C3) Inhibitor

1,080mg APL-2 administered subcutaneously twice weekly

Eligibility Criteria

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

You may qualify if:

• Be at least 18 years old (inclusive).
• Have LDH ≥1.5 x ULN at the screening visit.
• Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone \>10%).
• Have Hb less than the lower limit of normal (LLN) at the screening visit.
• Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject's dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study.
• Body mass index (BMI) ≤ 35 kg/m2 at the screening visit.
• Have a platelet count of \>50,000/mm3 at the screening visit.
• Have an absolute neutrophil count \>500/mm3 at the screening visit.

You may not qualify if:

• Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening.
• Hereditary complement deficiency.
• History of bone marrow transplantation.
• Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening:
• Erythropoietin or immunosuppressants for at least 8 weeks
• Systemic corticosteroids for at least 4 weeks
• Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks
• Iron supplements, vitamin B12, or folic acid for at least 4 weeks
• Low-molecular-weight heparin for at least 4 weeks

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (30)

Julian Coronel Medical Center

Cali, Colombia

Location

Research Center of the Colombian Clinical Life Cancer Foundation

Medellín, Colombia

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Princess Margaret Hospital

Kwai Chung, Hong Kong

Location

Prince and Wales Hospital

Shatin, Hong Kong

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Universitario Dr.Jose Eleuterio Gonzalez

Monterrey, Mexico

Location

Hospital Cayetano Heredia

San Martín de Porres, Lima region, 15102, Peru

Location

Hospital Cayetano Heredia

Jesús María, Lima, 15072, Peru

Location

Hospital Nacional Dos de Mayo

Lima, 15003, Peru

Location

Baguio General Hospital

Benguet, 2600, Philippines

Location

Perpetual Succour Hospital

Cebu City, 6000, Philippines

Location

Mary Mediatrix Medical Center

Lipa City, 4217, Philippines

Location

Makati Medical Centre

Makati City, 1229, Philippines

Location

The Medical City

Pasig, 1604, Philippines

Location

St. Lukes Medical Centre

Quezon City, 1112, Philippines

Location

Independent Public Clinical Hospital

Lubin, 20-081, Poland

Location

Institute of Hematology and Transfusiology

Warsaw, 02-776, Poland

Location

EMC Medical Institute

Wroclaw, 50-220, Poland

Location

Clinical Centre of Serbia

Belgrade, Serbia

Location

Singapore General Hospital (SGH)

Singapore, 169608, Singapore

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Hospital for Tropical disease

Bangkok, Thailand

Location

Phramongkutklao Hospital

Bangkok, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Srinagaring Hospital

Khon Kaen, 40002, Thailand

Location

Thammasat University Hospital

Pathum Thani, 12120, Thailand

Location

Songklanagaring Hospital

Songkhla, 90110, Thailand

Location

Related Publications (8)

• 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

• 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

• Fishman J, Wilson K, Drzewiecka A, Pochopien M, Dingli D. The cost-effectiveness of pegcetacoplan in complement treatment-naive adults with paroxysmal nocturnal hemoglobinuria in the USA. J Comp Eff Res. 2023 Oct;12(10):e230055. doi: 10.57264/cer-2023-0055. Epub 2023 Sep 1.

  PMID: 37655691 DERIVED

• Wojciechowski P, Wdowiak M, Hakimi Z, Wilson K, Fishman J, Nazir J, Toumi M. Mapping the EORTC QLQ-C30 onto the EQ-5D-5L index for patients with paroxysmal nocturnal hemoglobinuria in France. J Comp Eff Res. 2023 May;12(5):e220178. doi: 10.57264/cer-2022-0178. Epub 2023 Apr 13.

  PMID: 37052120 DERIVED

• Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, Idrobo H, Kongkabpan D, Gomez-Almaguer D, Al-Adhami M, Ajayi T, Alvarenga P, Savage J, Deschatelets P, Francois C, Grossi F, Dumagay T. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Blood Adv. 2023 Jun 13;7(11):2468-2478. doi: 10.1182/bloodadvances.2022009129.

  PMID: 36848639 DERIVED

• Wong R, Fishman J, Wilson K, Yeh M, Al-Adhami M, Zion A, Yee CW, Huynh L, Duh MS. Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison. Adv Ther. 2023 Apr;40(4):1571-1589. doi: 10.1007/s12325-023-02438-9. Epub 2023 Feb 7.

  PMID: 36750531 DERIVED

• Del Pozo Martin Y. 2021 ASH annual meeting. Lancet Haematol. 2022 Feb;9(2):e92-e93. doi: 10.1016/S2352-3026(21)00384-7. Epub 2021 Dec 16. No abstract available.

  PMID: 34922648 DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 11, 2019
• Study Start: August 27, 2019
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: October 21, 2022
• Results First Posted: October 21, 2022

Record last verified: 2022-10

Locations

TH (8); CO (2); PL (3); HK (3); SG (1); ME (1); PE (3); PH (6); SE (1); MY (2)