Clinical trial NCT03946748: Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Official title: An Open-Label, Single Arm Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor-Naive or Have Not Recently Received Complement Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-05-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment-naive to complement inhibitor therapy or have not recently received complement inhibitor therapy.

The secondary objectives of the study are:

* To evaluate the safety and tolerability of REGN3918.
* To evaluate the effect of REGN3918 on parameters of intravascular hemolysis
* To assess the concentrations of total REGN3918 in serum.
* To evaluate the incidence of treatment-emergent anti-drug antibodies to REGN3918 over time
* To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue and health-related quality of life


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high-sensitivity flow cytometry
* PNH granulocytes \> 10% at screening visit
* Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms (eg, fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 g/dL\], history of a MAVE \[including thrombosis\], dysphagia, or erectile dysfunction) or history of red blood cell (RBC) transfusion due to PNH within 3 months of screening.
* Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening visit.

Key Exclusion Criteria:

* Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C)
* History of bone marrow transplantation
* Body weight \< 40 kilograms at screening visit
* Peripheral blood absolute neutrophil count (ANC) \<500/μL \[\<0.5 x 109/L\] or peripheral blood platelet count \<50,000/μL
* Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of active or latent tuberculosis infection (LTBI) during screening period
* Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic prophylaxis therapy as recommended in the study
* Any active, ongoing infection within 2 weeks of screening or during the screening period
* Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, or patients with short life expectancy
* Women who are pregnant, breastfeeding, or who have a positive pregnancy test at screening visit or day 1

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis
timeFrame: Week 4 through Week 26
measure: Percentage of Participants Who Achieved Transfusion Avoidance
timeFrame: Up to 26 Weeks
Secondary outcomes:
measure: Percentage of Participants Who Had Breakthrough Hemolysis (BTH)
timeFrame: Baseline up to 26 Weeks
measure: Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis
timeFrame: Week 4 through Week 26
measure: Time to First Lactate Dehydrogenase (LDH) ≤1.5 x ULN
timeFrame: Up to Week 26
measure: Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26
timeFrame: Week 4 through Week 26
measure: Change From Baseline in LDH Levels at Week 26
timeFrame: Baseline, Week 26
measure: Percent Change From Baseline in LDH Levels at Week 26
timeFrame: Baseline, Week 26
measure: Rate of Transfusion With Red Blood Cells (RBCs)
timeFrame: Baseline up to Week 26
measure: Number of Units of Transfusion With RBCs
timeFrame: Baseline up to Week 26
measure: Change From Baseline in RBC Hemoglobin Levels at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Free Hemoglobin Levels at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) at Week 26
timeFrame: Baseline, Week 26
measure: Percent Change From Baseline in CH50 up to Week 26
timeFrame: Baseline up to Week 26
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core 30 (EORTC QLQ-C30) at Week 26
timeFrame: Baseline, Week 26
measure: Change From Baseline in European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Index Score
timeFrame: Baseline, Week 26
measure: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Week 26
timeFrame: Baseline, Week 26
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline up to Week 26
measure: Number of Participants With TEAEs Based on Severity
timeFrame: Baseline up to Week 26
measure: Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters
timeFrame: Baseline up to Week 26
measure: Number of Participants With Clinically Meaningful Changes in Vital Signs
timeFrame: Baseline up to Week 26
measure: Number of Participants With Clinically Meaningful Changes in 12-lead Electrocardiograms (ECGs)
timeFrame: Baseline up to Week 26
measure: Serum Concentrations of Total REGN3918
timeFrame: Pre-dose (Day 0), End of infusion at Days 0, 2, 7, 28, 56, 84, 112, 140, and 182
measure: Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) Response to REGN3918
timeFrame: Baseline up to Week 26
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: Regeneron Study Site
city: Budapest
country: Hungary
facility: Regeneron Study Site
city: Kaposvár
country: Hungary
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Study Site
city: Kota Bharu
country: Malaysia
facility: Regeneron Study Site
state: Kelantan
city: Sibu
country: Malaysia
facility: Regeneron Study Site
state: Sarawak
city: Kuala Terengganu
country: Malaysia
facility: Regeneron Study Site
state: Terengganu
city: Airdrie
country: United Kingdom
facility: Regeneron Study Site
state: Lanarkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: