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

• ClinicalTrials.gov Identifier: NCT03818607
• Recruitment Status: Active, not recruiting
• First Posted: January 28, 2019
• Last Update Posted: January 22, 2021
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: January 17, 2019
• First Posted Date: January 28, 2019
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: April 24, 2019
• Estimated Primary Completion Date: January 10, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2019)

• Hemolysis as measured by Lactate dehydrogenas (LDH) (Parallel Comparison) [ Time Frame: 12 months ]
• Hemolysis as measured by LDH (Crossover Comparison) [ Time Frame: 18 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 24, 2019)

• Total hemolytic complement (Total Complement) [ Time Frame: 18 months ]
• Total hemoglobin [ Time Frame: 18 months ]
• Serum-free hemoglobin [ Time Frame: 18 months ]
• Haptoglobin [ Time Frame: 18 months ]
• Bilirubin [ Time Frame: 18 months ]
• Degree of hemoglobinuria [ Time Frame: 18 months ]
• Type III erythrocytes [ Time Frame: 18 months ]
• Crossover comparison of hemolysis as measured by LDH [ Time Frame: 18 months ]
• Lactate dehydrogenase-time profile [ Time Frame: 18 months ]
• Incidence of red blood cell transfusion [ Time Frame: 18 months ]
• Pharmacokinetic area under the curve (AUC) of ABP 959 [ Time Frame: 18 months ]
• Pharmacokinetic area under the curve (AUC) of eculizumab [ Time Frame: 18 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Brief Summary: This is a randomized, double-blind, active-controlled phase 3 study of ABP 959 in participants with paroxysmal nocturnal hemoglobinuria.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

double-blind

Primary Purpose: Treatment

• Condition: Paroxysmal Nocturnal Hemoglobinuria

Intervention

• Drug: ABP 959
  intravenous infusion
  Other Name: Treatment T
• Drug: Eculizumab
  intravenous infusion
  Other Names:

  • Soliris
  • Treatment R

Study Arms

• T (ABP 959) / R (eculizumab)
  ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2
  Interventions:

  • Drug: ABP 959
  • Drug: Eculizumab
• R (eculizumab) / T (ABP 959)
  Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2
  Interventions:

  • Drug: ABP 959
  • Drug: Eculizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 19, 2021): 42
• Original Estimated Enrollment (submitted: January 24, 2019): 40
• Estimated Study Completion Date: July 13, 2022
• Estimated Primary Completion Date: January 10, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Finland, France, Ireland, Italy, Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Germany

Administrative Information

• NCT Number: NCT03818607
• Other Study ID Numbers: 20150168
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: https://www.amgen.com/datasharing

• Responsible Party: Amgen
• Study Sponsor: Amgen
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: January 2021