Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Percentage of Participants Who Had Breakthrough Hemolysis (BTH)

Breakthrough hemolysis was defined as the measurement of LDH ≥ 2 ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (i.e., LDH ≤ 1.5 ULN).

Time frame: Baseline up to 26 Weeks

Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis

A participant was considered to have achieved normalization of intravascular hemolysis if their LDH readings between Week 4 through Week 26 inclusive had values ≤ 1.0 ULN. A participant must have ≥ 50% of scheduled LDH measures in those weeks, must not have had \> 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. A participant was considered not to have achieved normalization of intravascular hemolysis if they failed any of these criteria.

Time frame: Week 4 through Week 26

Time to First Lactate Dehydrogenase (LDH) ≤1.5 x ULN

A time-to-first-event analysis was used to estimate the proportion of participants achieving transfusion avoidance at Week 26.

Time frame: Up to Week 26

Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26

Percentage of days was calculated as number of days with LDH ≤ 1.5 x ULN divided by the participant's total treatment duration (total number of days on treatment from Week 4 through Week 26). LDH ≤ 1.5 x ULN was used as an indicator of adequate control of intravascular hemolysis.

Time frame: Week 4 through Week 26

Change From Baseline in LDH Levels at Week 26

Change from baseline in LDH levels at Week 26 was reported.

Time frame: Baseline, Week 26

Percent Change From Baseline in LDH Levels at Week 26

Percent change from baseline in LDH levels at Week 26 was reported.

Time frame: Baseline, Week 26

Rate of Transfusion With Red Blood Cells (RBCs)

The rate of transfusion with RBCs for a participant was the total number of transfusions divided by total person-years of time on treatment.

Time frame: Baseline up to Week 26

Number of Units of Transfusion With RBCs

Transfusions with RBCs proceeded according to the following predefined criteria that triggered a transfusion; however, the actual number of units to be transfused is at the discretion of the investigator: • Transfuse with RBC(s) if the post-baseline hemoglobin level is \<9 g/dL with symptoms resulting from anemia or • Transfuse with RBC(s) if the post-baseline hemoglobin level is \<7 g/dL.

Time frame: Baseline up to Week 26

Change From Baseline in RBC Hemoglobin Levels at Week 26

Hemoglobin levels in participants with PNH was measured. Change from baseline in RBC hemoglobin at Week 26 was reported.

Time frame: Baseline, Week 26

Change From Baseline in Free Hemoglobin Levels at Week 26

Change from baseline in free hemoglobin levels at Week 26 was assessed.

Time frame: Baseline, Week 26

Change From Baseline in Total Complement Hemolytic Activity Assay (CH50) at Week 26

Change from baseline in total CH50 at Week 26 was reported. Here "International units per milliliter" was abbreviated as "IU/mL".

Time frame: Baseline, Week 26

Percent Change From Baseline in CH50 up to Week 26

Percent change from baseline in CH50 up to Week 26 was reported.

Time frame: Baseline up to Week 26

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 26

The FACIT-F was a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire was part of the FACIT measurement system, a compilation of questions measuring health-related QoL in participants with cancer and other chronic illnesses. The FACIT-fatigue assessed the level of fatigue using a 4-point Likert scale ranging from 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much) The sum of all responses resulted in the FACIT-F score for a total possible score of 0 to 52, with higher scores indicated greater fatigue.

Time frame: Baseline, Week 26

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

The EORTC QLQ-C30 was a 30-item questionnaire used to assess symptoms and side effects of treatment and the impact on everyday life. It consists of 15 domains: 5 multi-item functioning scales (physical, role, social, emotional and cognitive), answered on a 4-point scale (1=Not at all,2=A Little,3=Quite a Bit,4=Very Much). Each score ranges from 0-100 with a higher score indicates higher level of functioning and a better QoL. A global health status/QoL scale that was answered on a 7-point scale (1=Very Poor to 7=Excellent). Each score ranges from 0-100 with a higher score indicates a better QoL. 9 symptom scales (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, Financial Impact), answered on a 4-point scale (1=Not at all, 2=A Little, 3=Quite a Bit, 4=Very Much). Each score ranges from 0 to 100 with a higher score indicates a higher level of symptoms, and a negative change from baseline indicates an improvement in symptoms.

Time frame: Baseline, Week 26

Change From Baseline in European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Index Score

EQ-5D-3L was a self-administered standardized instrument for use as measure of health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension rated on 3 levels scale: 1 (no problems), 2 (some problems), 3 (extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" to severe problems in 5 dimensions. EQ-5D index calculated by applying preference-based weights (tariffs) to scores of five health state dimensions. Index values range from -1 to 1, with 0 representing a health state equivalent to death and 1 representing perfect health. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best).

Time frame: Baseline, Week 26

Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Week 26

The EQ-5D-3L was a standardized instrument for use as a measure of health outcome and was administered to all participants to assess the effect of the treatment on the participants' quality of life. The EQ-5D-3L includes a visual analog scale (VAS) which is a vertical scale with numbers ranging from 0 to 100. Participants were asked to draw a line to the place on the scale that best represented how good or bad his health was on that day. The worst state a participant can imagine was marked zero, and the best state the participant can imagine was marked 100. Mean change in VAS score from baseline was reported.

Time frame: Baseline, Week 26

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs was defined as AEs that developed or worsened during the on-treatment period. SAE was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs included both Serious TEAEs and non-serious TEAEs.

Time frame: Baseline up to Week 26

Number of Participants With TEAEs Based on Severity

An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Severity of AEs was graded according to the following scale, Mild: event that does not generally interfere with usual activities of daily living; Moderate: event that interferes with usual activities of daily living, causing discomfort, permanent risk of harm; Severe: AE that interrupts usual activities of daily living, significantly affects clinical status, or may require intensive therapeutic intervention.

Time frame: Baseline up to Week 26

Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters

Clinical laboratory parameters included biochemistry, hematology and urinalysis. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically meaningful by the investigator were reported.

Time frame: Baseline up to Week 26

Number of Participants With Clinically Meaningful Changes in Vital Signs

Vital sign assessments included pulse rate, blood pressure (systolic and diastolic blood pressure) and body temperature. Number of participants with potential clinically meaningful changes in vital signs which were deemed clinically significant by the investigator were reported.

Time frame: Baseline up to Week 26

Number of Participants With Clinically Meaningful Changes in 12-lead Electrocardiograms (ECGs)

12-lead ECGs were evaluated. Any change in ECG assessments which are deemed clinically meaningful by the investigator were reported.

Time frame: Baseline up to Week 26

Serum Concentrations of Total REGN3918

Serum Concentrations of total REGN3918 was reported.

Time frame: Pre-dose (Day 0), End of infusion at Days 0, 2, 7, 28, 56, 84, 112, 140, and 182

Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) Response to REGN3918

Number of Participants with treatment-emergent ADA response to REGN3918 was reported.

Time frame: Baseline up to Week 26