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Completed

NCT Number: NCT03818607

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

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

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Key information

Conditions

Paroxysmal Nocturnal Hemoglobinuria Anemia Anemia, Hemolytic Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinuria, Paroxysmal Myelodysplastic Syndromes

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Fakultní Nemocnice Brno, Brno, Jihormoravsky KRAJ, Czechia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABP 959

Drug

intravenous infusion

Other names: Treatment T

Eculizumab

Drug

intravenous infusion

Other names: Soliris, Treatment R

Primary outcomes

  1. LDH Level at Week 27 (Parallel Comparison)

    Time frame: Week 27

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

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

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

    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.

Secondary outcomes

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

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

    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.

  2. Mean Total Hemoglobin Levels

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

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

  3. Mean Serum-free Hemoglobin Levels

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

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

  4. Mean Haptoglobin Levels

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

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

  5. Mean Bilirubin Levels

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

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

  6. Degree of Hemoglobinuria

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

    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.

  7. Mean Percentage of Type III Erythrocytes

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

    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.

  8. LDH Levels at Week 53 and Week 79

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

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

  9. Mean LDH Levels by Visit up to Week 79

    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

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

  10. Mean Number of Packed RBC Units Transfused Per Month

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

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

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

    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

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

  12. Total and Unbound Trough Serum Concentrations of ABP 959 and Eculizumab

    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

    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.

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

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

    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.

  14. Number of Participants With Antidrug Antibodies (ADAs)

    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.

    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.

Sponsors and collaborators

Lead sponsor

Amgen

Industry

Registry information

Official study 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)

Acronym: DAHLIA

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jan 28, 2019
Registry last updated
May 23, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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