Clinical trial NCT03818607: A Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Participants With PNH
Official title: A Randomized, Double-Blind, Active-Controlled Phase 3 Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Marchiafava-Micheli Syndrome
Paroxysmal Cold Hemoglobinuria
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2019-01-28
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: LDH Level at Week 27 (Parallel Comparison)
timeFrame: Week 27
measure: Time-adjusted Area Under the Effect Curve (AUEC) of LDH (Crossover Comparison Per Assigned Treatment)
timeFrame: From Week 13 to Week 27, from Week 39 to Week 53, and from Week 65 to Week 79
Secondary outcomes:
measure: Mean Total Complement (50% Total Hemolytic Complement Activity [CH50])
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Mean Total Hemoglobin Levels
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Mean Serum-free Hemoglobin Levels
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Mean Haptoglobin Levels
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Mean Bilirubin Levels
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Degree of Hemoglobinuria
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
measure: Mean Percentage of Type III Erythrocytes
timeFrame: Baseline, Week 27, Week 39, Week 53, Week 65 and Week 79
measure: LDH Levels at Week 53 and Week 79
timeFrame: Week 53 (first week of Period 2) and Week 79 (last week of Period 2)
measure: Mean LDH Levels by Visit up to Week 79
timeFrame: Baseline, Week 3, Week 7, Week 13, Week 15, Week 19, Week 25, Week 27, Week 29, Week 33, Week 39, Week 41, Week 43, Week 45, Week 47, Week 49, Week 51, Week 53, Week 55, Week 59, Week 65, Week 67, Week 69, Week 71, Week 73, Week 75, Week 77, and Week 79
measure: Mean Number of Packed RBC Units Transfused Per Month
timeFrame: Baseline to End of Study (up to Week 79)
measure: Total and Unbound Pharmacokinetics (PK) Area Under the Curve (AUC) of ABP 959 and Eculizumab From Week 13 to Week 15 (Period 1)
timeFrame: PK samples were collected predose and immediately postdose Week 13, 7 days post the Week 13 dose (Week 14), and predose at Week 15
measure: Total and Unbound Trough Serum Concentrations of ABP 959 and Eculizumab
timeFrame: PK samples were collected predose at the prespecified timepoints: baseline, Week 3, Week 7, Week 13, Week 15, Week 19, Week 27, Week 33, Week 39, Week 45, Week 51, Week 53, Week 55, Week 59, Week 65, Week 71, Week 77, and Week 79
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to End of Study (up to Week 79)
measure: Number of Participants With Antidrug Antibodies (ADAs)
timeFrame: Blood samples for ADA assessments were taken predose at baseline, Week 3, Week 7, Week 13, Week 19, Week 25, Week 27, Week 33, Week 39, Week 45, Week 51, Week 53, Week 55, Week 59, Week 65, Week 71, Week 77 and Week 79.
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno
state: Jihormoravsky KRAJ
city: Olomouc
country: Czechia
facility: Fakultní Nemocnice Olomouc
city: Ostrava-Poruba
country: Czechia
facility: Fakultní Nemocnice Ostrava
city: Jyväskylä
country: Finland
facility: Keski-Suomen keskussairaala Jyväskylä
city: Lahti
country: Finland
facility: Päijät-Häme Central Hospital
city: Cesson-Sevigne
country: France
facility: Hôpital Privé Sévigné
state: Bretagne
city: Dublin
country: Ireland
facility: Saint James's Hospital
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli-cesena
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Monza Brianza
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle Cuneo
city: Ravenna
country: Italy
facility: Azienda USL della Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
state: Gelderland
city: Oslo
country: Norway
facility: Oslo University Hospital - Rikshospitalet
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil
city: Ljubljana
country: Slovenia
facility: Univerzitetni klinični center Ljubljana
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Huddinge
city: Bornova
country: Turkey
facility: Ege Universitesi Hastanesi - Sağlık Uygulama ve Araştırma Merkezi
state: Izmir
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi
city: Leeds
country: United Kingdom
facility: The Leeds Teaching Hospitals NHS Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: