Trial record 1 of 1 for:
ABP 959
A Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Participants With PNH (DAHLIA)
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| ClinicalTrials.gov Identifier: NCT03818607 |
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Recruitment Status :
Completed
First Posted : January 28, 2019
Results First Posted : May 23, 2023
Last Update Posted : May 23, 2023
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Sponsor:
Amgen
Information provided by (Responsible Party):
Amgen
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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 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 : | January 22, 2019 |
| Actual Primary Completion Date : | July 12, 2022 |
| Actual Study Completion Date : | July 12, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Paroxysmal nocturnal hemoglobinuria
Drug Information available for:
Eculizumab
| Arm | Intervention/treatment |
|---|---|
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T (ABP 959) / R (eculizumab)
ABP 959 for 52 weeks in Period 1 followed by eculizumab for 26 weeks in Period 2
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Drug: ABP 959
intravenous infusion
Other Name: Treatment T Drug: Eculizumab intravenous infusion
Other Names:
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R (eculizumab) / T (ABP 959)
Eculizumab for 52 weeks in Period 1 followed by ABP 959 for 26 weeks in Period 2
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Drug: ABP 959
intravenous infusion
Other Name: Treatment T Drug: Eculizumab intravenous infusion
Other Names:
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Primary Outcome Measures :
- 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).
- 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 Outcome Measures :
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Information from the National Library of Medicine
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| 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03818607
Locations
Show 24 study locations
Sponsors and Collaborators
Amgen
Investigators
| Study Director: | MD | Amgen |
Study Documents (Full-Text)
Documents provided by Amgen:
Documents provided by Amgen:
Study Protocol [PDF] March 5, 2020
Statistical Analysis Plan [PDF] September 20, 2022
Additional Information:
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT03818607 |
| Other Study ID Numbers: |
20150168 |
| First Posted: | January 28, 2019 Key Record Dates |
| Results First Posted: | May 23, 2023 |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | April 2023 |
| 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:
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Marchiafava-Micheli Syndrome Paroxysmal Cold Hemoglobinuria |
Additional relevant MeSH terms:
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Hemoglobinuria Hemoglobinuria, Paroxysmal Proteinuria Urination Disorders Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Urological Manifestations |
Anemia, Hemolytic Anemia Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases Eculizumab Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |