A Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Participants With PNH

NCT03818607 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 20150168
• Study Type: interventional
• Target: 42
• Locations: 14 countries
• Sites: 24

Brief Summary

This is a randomized, double-blind, active-controlled phase 3 study of ABP 959 in participants with paroxysmal nocturnal hemoglobinuria.

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Marchiafava-Micheli Syndrome; Paroxysmal Cold Hemoglobinuria

Outcome Measures

Primary Outcomes (2)

• LDH Level at Week 27 (Parallel Comparison)

  The primary analysis for the parallel comparison was hemolysis as measured by LDH at Week 27 by initial treatment received (Period 1).

  Week 27

• Time-adjusted Area Under the Effect Curve (AUEC) of LDH (Crossover Comparison Per Assigned Treatment)

  The primary analysis for the crossover comparison was hemolysis, as measured by the time-adjusted AUEC of LDH, according to treatment assigned during each of the 14-week assessments during Periods 1 and 2.

  From Week 13 to Week 27, from Week 39 to Week 53, and from Week 65 to Week 79

Secondary Outcomes (14)

• Mean Total Complement (50% Total Hemolytic Complement Activity [CH50])

  Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

• Mean Total Hemoglobin Levels

  Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

• Mean Serum-free Hemoglobin Levels

  Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

• Mean Haptoglobin Levels

  Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

• Mean Bilirubin Levels

  Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Study Arms (2)

T (ABP 959) / R (eculizumab)

OTHER

ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2

Drug: ABP 959; Drug: Eculizumab

R (eculizumab) / T (ABP 959)

OTHER

Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2

Drug: ABP 959; Drug: Eculizumab

Interventions

ABP 959 DRUG

intravenous infusion

Also known as: Treatment T

R (eculizumab) / T (ABP 959); T (ABP 959) / R (eculizumab)

Eculizumab DRUG

intravenous infusion

Also known as: Soliris, Treatment R

R (eculizumab) / T (ABP 959); T (ABP 959) / R (eculizumab)

Eligibility Criteria

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

You may qualify if:

• Men and women ≥ 18 years of age.
• Historical diagnosis of PNH.
• Administration of eculizumab for ≥ 6 months and currently receiving 900 mg of eculizumab.
• Hemoglobin ≥ 9.0 g/dL for at least 6 weeks before randomization.
• Lactate dehydrogenase \< 1.5 × the upper limit of normal at screening.
• Platelet count ≥ 50 × 10\^9/L.
• Absolute neutrophil count (ANC) ≥ 0.5 x 10\^9/L (500/μL).
• Participants must be vaccinated against Neisseria meningitidis.
• Participants must sign an IRB/IEC-approved ICF before participation in any procedures.

You may not qualify if:

• Known or suspected hereditary complement deficiency.
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure \[New York Heart Association ≥ Class III\], serious uncontrolled cardiac arrhythmia), peripheral vascular disease, cerebrovascular accident, or transient ischemic attack in the previous 6 months.
• Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal veins).
• Known to be positive for human immunodeficiency virus.
• Woman who is pregnant or breastfeeding.
• Participant is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or participant is receiving other investigational agent(s).
• Participant has known sensitivity to any of the products to be administered during the study, including mammalian cell-derived drug products.
• History of meningococcal infection.
• Presence or suspicion of active bacterial infection, or recurrent bacterial infection.
• History of bone marrow transplantation.
• Red blood cell transfusion required within 12 weeks before randomization.
• Participant experienced ≥ 2 breakthrough events, (ie, signs and symptoms of intravascular hemolysis, that require dose and/or schedule adjustments of eculizumab) in the previous 12 months before screening.

Sponsors & Collaborators

• Amgen: lead

Study Sites (24)

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Fakultní Nemocnice Brno

Brno, Jihormoravsky KRAJ, 625 00, Czechia

Location

Fakultní Nemocnice Olomouc

Olomouc, 772 00, Czechia

Location

Fakultní Nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Keski-Suomen keskussairaala Jyväskylä

Jyväskylä, FI-40620, Finland

Location

Päijät-Häme Central Hospital

Lahti, FI-15850, Finland

Location

Hôpital Privé Sévigné

Cesson-Sévigné, Brittany Region, 35576, France

Location

Saint James's Hospital

Dublin, 8, Ireland

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, 47014, Italy

Location

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza Brianza, 20052, Italy

Location

Azienda Ospedaliera S. Croce e Carle Cuneo

Cuneo, 12100, Italy

Location

Azienda USL della Romagna

Ravenna, 48121, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Radboud Universitair Medisch Centrum

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Oslo University Hospital - Rikshospitalet

Oslo, 0372, Norway

Location

Instituto Português de Oncologia do Porto Francisco Gentil

Porto, 4200-072, Portugal

Location

Univerzitetni klinični center Ljubljana

Ljubljana, 1000, Slovenia

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Karolinska Universitetssjukhuset - Huddinge

Stockholm, 141 86, Sweden

Location

Ege Universitesi Hastanesi - Sağlık Uygulama ve Araştırma Merkezi

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Mersin Universitesi Tip Fakultesi

Mersin, 33110, Turkey (Türkiye)

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, England, LS9 7TF, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Kulasekararaj A, Lanza F, Arvanitakis A, Langemeijer S, Chonat S, Tombak A, Hanes V, Cao J, Miller MJ, Colbert A, Shander B, Mytych DT, Chow V, Henary H. Comparative clinical efficacy and safety of biosimilar ABP 959 and eculizumab reference product in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2024 Nov;99(11):2108-2117. doi: 10.1002/ajh.27456. Epub 2024 Aug 22.

  PMID: 39171864 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 28, 2019
• Study Start: January 22, 2019
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: May 23, 2023
• Results First Posted: May 23, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

NO (1); SL (1); TU (2); NL (1); US (1); SE (1); CZ (3); FI (2); IT (5); ES (2); IE (1); PT (1); GB (2); FR (1)