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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— DAHLIA  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03818607
• Other study ID #: 20150168
• Status: Completed
• Phase: Phase 3
• Start date: January 22, 2019
• Est. completion date: July 12, 2022

Study information

• Verified date: April 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 12, 2022
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• ABP 959
intravenous infusion
• Eculizumab
intravenous infusion

Locations

Country	Name	City	State
Czechia	Fakultní Nemocnice Brno	Brno	Jihormoravsky KRAJ
Czechia	Fakultní Nemocnice Olomouc	Olomouc
Czechia	Fakultní Nemocnice Ostrava	Ostrava-Poruba
Finland	Keski-Suomen keskussairaala Jyväskylä	Jyväskylä
Finland	Päijät-Häme Central Hospital	Lahti
France	Hôpital Privé Sévigné	Cesson-Sevigne	Bretagne
Ireland	Saint James's Hospital	Dublin
Italy	Azienda Ospedaliera S. Croce e Carle Cuneo	Cuneo
Italy	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	Azienda USL della Romagna	Ravenna
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen	Gelderland
Norway	Oslo University Hospital - Rikshospitalet	Oslo
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil	Porto
Slovenia	Univerzitetni klinicni center Ljubljana	Ljubljana
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario La Fe	Valencia
Sweden	Karolinska Universitetssjukhuset - Huddinge	Stockholm
Turkey	Ege Universitesi Hastanesi - Saglik Uygulama ve Arastirma Merkezi	Bornova	Izmir
Turkey	Mersin Universitesi Tip Fakultesi	Mersin
United Kingdom	The Leeds Teaching Hospitals NHS Trust	Leeds	England
United Kingdom	King's College Hospital NHS Foundation Trust	London	England
United States	Children's Healthcare of Atlanta at Egleston	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Czechia,  Finland,  France,  Ireland,  Italy,  Netherlands,  Norway,  Portugal,  Slovenia,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	Mean Total Hemoglobin Levels	Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	Mean Serum-free Hemoglobin Levels	Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	Mean Haptoglobin Levels	Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	Mean Bilirubin Levels	Baseline was defined as the last non-missing assessment taken prior to the first dose of IP.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	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.	Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
Secondary	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.	Baseline, Week 27, Week 39, Week 53, Week 65 and Week 79
Secondary	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.	Week 53 (first week of Period 2) and Week 79 (last week of Period 2)
Secondary	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.	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
Secondary	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.	Baseline to End of Study (up to Week 79)
Secondary	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.	PK samples were collected predose and immediately postdose Week 13, 7 days post the Week 13 dose (Week 14), and predose at Week 15
Secondary	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.	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
Secondary	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.	Day 1 to End of Study (up to Week 79)
Secondary	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.	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.

External Links

•   AmgenTrials clinical trials website