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

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria	Drug: ABP 959; Drug: Eculizumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double-blind
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 24, 2019
• Estimated Primary Completion Date: January 10, 2022
• Estimated Study Completion Date: July 13, 2022

Arms and Interventions

Arm	Intervention/treatment
T (ABP 959) / R (eculizumab); ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2	Drug: ABP 959; intravenous infusion; Other Name: Treatment T; Drug: Eculizumab; intravenous infusion; Other Names: Soliris; Treatment R
R (eculizumab) / T (ABP 959); Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2	Drug: ABP 959; intravenous infusion; Other Name: Treatment T; Drug: Eculizumab; intravenous infusion; Other Names: Soliris; Treatment R

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Total hemolytic complement (Total Complement) [ Time Frame: 18 months ]
2. Total hemoglobin [ Time Frame: 18 months ]
3. Serum-free hemoglobin [ Time Frame: 18 months ]
4. Haptoglobin [ Time Frame: 18 months ]
5. Bilirubin [ Time Frame: 18 months ]
6. Degree of hemoglobinuria [ Time Frame: 18 months ]
7. Type III erythrocytes [ Time Frame: 18 months ]
8. Crossover comparison of hemolysis as measured by LDH [ Time Frame: 18 months ]
9. Lactate dehydrogenase-time profile [ Time Frame: 18 months ]
10. Incidence of red blood cell transfusion [ Time Frame: 18 months ]
11. Pharmacokinetic area under the curve (AUC) of ABP 959 [ Time Frame: 18 months ]
12. Pharmacokinetic area under the curve (AUC) of eculizumab [ Time Frame: 18 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Research Site

Whittier, California, United States, 90602

United States, Georgia

Research Site

Athens, Georgia, United States, 30607

Research Site

Atlanta, Georgia, United States, 30322

Czechia

Research Site

Brno, Jihormoravsky KRAJ, Czechia, 625 00

Research Site

Olomouc, Czechia, 772 00

Research Site

Ostrava-Poruba, Czechia, 708 52

Finland

Research Site

Jyväskylä, Finland, FI-40620

Research Site

Lahti, Finland, FI-15850

France

Research Site

Cesson-Sevigne, Bretagne, France, 35576

Research Site

Amiens Cedex 1, Picardie, France, 80054

Research Site

Poitiers, Poitou-charentes, France, 86021 CEDE

Ireland

Research Site

Dublin, Ireland, 8

Italy

Research Site

Meldola, Forli-cesena, Italy, 47014

Research Site

Monza, Monza Brianza, Italy, 20052

Research Site

Bologna, Italy, 40138

Research Site

Cremona, Italy, 26100

Research Site

Cuneo, Italy, 12100

Research Site

Ravenna, Italy, 48121

Research Site

Rimini, Italy, 47923

Research Site

Roma, Italy, 00168

Research Site

Torino, Italy, 10128

Netherlands

Research Site

Nijmegen, Gelderland, Netherlands, 6525 GA

Norway

Research Site

Oslo, Norway, 0372

Portugal

Research Site

Porto, Portugal, 4200-072

Slovenia

Research Site

Ljubljana, Slovenia, 1000

Spain

Research Site

Majadahonda, Madrid, Spain, 28222

Research Site

Madrid, Spain, 28007

Research Site

Salamanca, Spain, 37007

Research Site

Valencia, Spain, 46026

Sweden

Research Site

Stockholm, Sweden, 141 86

Taiwan

Research Site

Changhua City, Changhwa, Taiwan, 500

Research Site

Kaohsiung, Taiwan, 807

Research Site

Tainan City, Taiwan, 736

Turkey

Research Site

Bornova, Izmir, Turkey, 35100

Research Site

Adana, Turkey, 01330

Research Site

Mersin, Turkey, 33110

Research Site

Samsun, Turkey, 55139

United Kingdom

Research Site

Leeds, England, United Kingdom, LS9 7TF

Research Site

London, England, United Kingdom, SE5 9RS

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03818607
• Other Study ID Numbers: 20150168
• First Posted: January 28, 2019
• Last Update Posted: January 22, 2021
• Last Verified: January 2021

Individual Participant Data (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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); 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

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

Keywords provided by Amgen:

Marchiafava-Micheli Syndrome; Paroxysmal Cold Hemoglobinuria

Additional relevant MeSH terms:

Hemoglobinuria; Hemoglobinuria, Paroxysmal; Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations; Anemia, Hemolytic; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases