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

Amgen

Status and phase: Completed; Phase 3

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Treatments: Drug: ABP 959; Drug: Eculizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03818607

20150168

Details and patient eligibility

About

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

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups

T (ABP 959) / R (eculizumab)

Other group

Description:

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

Treatment:

Drug: Eculizumab

Drug: ABP 959

R (eculizumab) / T (ABP 959)

Other group

Description:

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

Treatment:

Drug: Eculizumab

Drug: ABP 959