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

Amgen42 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

ABP 959DRUG

intravenous infusion

EculizumabDRUG

intravenous infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (24)

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

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).

Time frame: 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.

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

Secondary Outcomes

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

Total complement (%) was measured in serum using an assay method and compared the total hemolytic complement activity to the lower limit of the normal human reference (LLN) of 58 U/mL for all CH50 values. The percent of LLN of CH50 at each time point was calculated as mean CH50 results/LLN x 100%. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Mean Total Hemoglobin Levels

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Mean Serum-free Hemoglobin Levels

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Mean Haptoglobin Levels

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Fakultní Nemocnice Brno

Brno, Jihormoravsky KRAJ, Czechia

Fakultní Nemocnice Olomouc

Olomouc, Czechia

Fakultní Nemocnice Ostrava

Ostrava-Poruba, Czechia

Keski-Suomen keskussairaala Jyväskylä

Jyväskylä, Finland

Päijät-Häme Central Hospital

Lahti, Finland

Hôpital Privé Sévigné

Cesson-Sévigné, Brittany Region, France

Saint James's Hospital

Dublin, Ireland

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forli-cesena, Italy

Azienda Ospedaliera San Gerardo di Monza

Monza, Monza Brianza, Italy

...and 14 more locations

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Mean Bilirubin Levels

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Degree of Hemoglobinuria

The degree of hemoglobinuria was categorized as negative, trace, small, moderate, and large based on the analysis of urine samples collected from each participant at the specified time points. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79

Mean Percentage of Type III Erythrocytes

As a measure of hemolysis the mean percentage of Type III erythrocytes was measured at the specified timepoints. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline, Week 27, Week 39, Week 53, Week 65 and Week 79

LDH Levels at Week 53 and Week 79

The analysis of the crossover comparison of hemolysis, as measured by LDH at Week 53 and Week 79.

Time frame: Week 53 (first week of Period 2) and Week 79 (last week of Period 2)

Mean LDH Levels by Visit up to Week 79

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: 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

Mean Number of Packed RBC Units Transfused Per Month

Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: Baseline to End of Study (up to Week 79)

Total and Unbound Pharmacokinetics (PK) Area Under the Curve (AUC) of ABP 959 and Eculizumab From Week 13 to Week 15 (Period 1)

The total and unbound PK concentration AUC values from Week 13 to Week 15 in Period 1 are presented by actual treatment received.

Time frame: PK samples were collected predose and immediately postdose Week 13, 7 days post the Week 13 dose (Week 14), and predose at Week 15

Total and Unbound Trough Serum Concentrations of ABP 959 and Eculizumab

The total and unbound serum trough concentrations are presented by treatment sequence received for the prespecified time points. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: 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

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs are defined as any adverse event (AE) that began or increased in severity or frequency at or after the time of first treatment up to end of study (up to Week 79). A treatment-emergent serious adverse event (SAE) was a TEAE that met at least 1 of the following criteria: was fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was another medically important serious event. The treatment-emergent events of interest (EOI) prespecified for this study included serious infections (meningococcus aspergillus, and other serious infections/sepsis), and infusion reactions.

Time frame: Day 1 to End of Study (up to Week 79)

Number of Participants With Antidrug Antibodies (ADAs)

Any samples that tested positive for binding antibodies were also tested for neutralizing antibodies. Treatment boosted ADAs were defined as a positive immunoassay result at baseline and at least 1 postbaseline immunoassay result that was ≥ 4 times the magnitude of the baseline result. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.

Time frame: 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.