Clinical Trials List
Protocol NumberR3918-PNH-1852
NCT Number(ClinicalTrials.gov Identfier)NCT03946748
2019-05-01 - 2021-10-31
Phase II
Recruiting4
ICD-10N39.44
Nocturnal enuresis
ICD-9788.36
Nocturnal enuresis
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
-
Trial Applicant
Syneos Health
-
Sponsor
Regeneron Pharmaceuticals, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ya-Ping Chen Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 高小雯 Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- - - Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Objectives
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
Test Drug
REGN3918N
Active Ingredient
REGN3918
Dosage Form
vial
Dosage
265
Endpoints
Primary Outcome Measures :
Proportion of patients achieving adequate control of their intravascular hemolysis [ Time Frame: Week 4 through week 26 ]
Defined as lactate dehydrogenase (LDH) ≤ 1.5 x upper limit of normal (ULN)
Proportion of patients achieving transfusion avoidance [ Time Frame: Up to 26 weeks ]
Defined as no post baseline transfusion of red blood cells (RBCs)
Secondary Outcome Measures :
Rate of breakthrough hemolysis [ Time Frame: Up to 26 Weeks ]
Defined as the measurement of LDH) ≥ 2 x ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control.
Proportion of patients achieving normalization of their intravascular hemolysis [ Time Frame: Week 4 through week 26 ]
Defined as LDH ≤ 1.0 x ULN
Time to first LDH ≤ 1.5 x ULN [ Time Frame: Up to week 26 ]
Percentage of days with LDH ≤ 1.5 x ULN [ Time Frame: Week 4 through week 26 ]
Change in LDH levels [ Time Frame: Baseline to week 26 ]
Percent change in LDH levels [ Time Frame: Baseline to week 26 ]
Rate of transfusion with RBCs [ Time Frame: Up to 26 weeks ]
Number of units of transfusion with RBCs [ Time Frame: Up to 26 weeks ]
Change in RBC hemoglobin levels [ Time Frame: Baseline to week 26 ]
Change in free hemoglobin levels [ Time Frame: Baseline to week 26 ]
Change in total complement hemolytic activity assay (CH50) [ Time Frame: Baseline to week 26 ]
Percent change in CH50 [ Time Frame: Baseline to week 26 ]
Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue [ Time Frame: Baseline to week 26 ]
The FACIT-F is 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 is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30) [ Time Frame: Baseline to week 26 ]
EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All the scales range from 0 to 100. A high score on the functional scales represents a high level of functioning, and a high score on the symptom scales represents a high level of symptomatology. A high score on the global QOL represents a high general quality of life.
Changes in scores of patient-reported outcomes as measured by EQ-5D-3L [ Time Frame: Baseline to week 26 ]
The EQ-5D-3L is a self-administered standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.
Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 26 weeks ]
Safety measured by number of patients who experience abnormal laboratory values [ Time Frame: Up to 26 weeks ]
Safety measured by number of patients who experience abnormal vital signs [ Time Frame: Up to 26 weeks ]
Concentrations of total REGN3918 in serum [ Time Frame: Up to week 26 ]
Incidence of treatment-emergent anti-drug antibodies to REGN3918 [ Time Frame: Up to week 26 ]
Proportion of patients achieving adequate control of their intravascular hemolysis [ Time Frame: Week 4 through week 26 ]
Defined as lactate dehydrogenase (LDH) ≤ 1.5 x upper limit of normal (ULN)
Proportion of patients achieving transfusion avoidance [ Time Frame: Up to 26 weeks ]
Defined as no post baseline transfusion of red blood cells (RBCs)
Secondary Outcome Measures :
Rate of breakthrough hemolysis [ Time Frame: Up to 26 Weeks ]
Defined as the measurement of LDH) ≥ 2 x ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control.
Proportion of patients achieving normalization of their intravascular hemolysis [ Time Frame: Week 4 through week 26 ]
Defined as LDH ≤ 1.0 x ULN
Time to first LDH ≤ 1.5 x ULN [ Time Frame: Up to week 26 ]
Percentage of days with LDH ≤ 1.5 x ULN [ Time Frame: Week 4 through week 26 ]
Change in LDH levels [ Time Frame: Baseline to week 26 ]
Percent change in LDH levels [ Time Frame: Baseline to week 26 ]
Rate of transfusion with RBCs [ Time Frame: Up to 26 weeks ]
Number of units of transfusion with RBCs [ Time Frame: Up to 26 weeks ]
Change in RBC hemoglobin levels [ Time Frame: Baseline to week 26 ]
Change in free hemoglobin levels [ Time Frame: Baseline to week 26 ]
Change in total complement hemolytic activity assay (CH50) [ Time Frame: Baseline to week 26 ]
Percent change in CH50 [ Time Frame: Baseline to week 26 ]
Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue [ Time Frame: Baseline to week 26 ]
The FACIT-F is 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 is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30) [ Time Frame: Baseline to week 26 ]
EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All the scales range from 0 to 100. A high score on the functional scales represents a high level of functioning, and a high score on the symptom scales represents a high level of symptomatology. A high score on the global QOL represents a high general quality of life.
Changes in scores of patient-reported outcomes as measured by EQ-5D-3L [ Time Frame: Baseline to week 26 ]
The EQ-5D-3L is a self-administered standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.
Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 26 weeks ]
Safety measured by number of patients who experience abnormal laboratory values [ Time Frame: Up to 26 weeks ]
Safety measured by number of patients who experience abnormal vital signs [ Time Frame: Up to 26 weeks ]
Concentrations of total REGN3918 in serum [ Time Frame: Up to week 26 ]
Incidence of treatment-emergent anti-drug antibodies to REGN3918 [ Time Frame: Up to week 26 ]
Inclution Criteria
Inclusion Criteria
A patient must meet the following criteria to be eligible for inclusion in the study:
1. Male or female ≥ 18 years of age or legal age of majority at screening, whichever is
greater
2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry
3. PNH granulocytes (denoted as polymorphonuclear [PMN]) > 10% at screening visit
4. 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 RBC transfusion due to PNH within 3 months of
screening
5. LDH level ≥ 2 × ULN at screening visit
6. Willing and able to comply with clinic visits and study-related procedures
7. Provide informed consent signed by study patient
8. Able to understand and complete study-related questionnaires
A patient must meet the following criteria to be eligible for inclusion in the study:
1. Male or female ≥ 18 years of age or legal age of majority at screening, whichever is
greater
2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry
3. PNH granulocytes (denoted as polymorphonuclear [PMN]) > 10% at screening visit
4. 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 RBC transfusion due to PNH within 3 months of
screening
5. LDH level ≥ 2 × ULN at screening visit
6. Willing and able to comply with clinic visits and study-related procedures
7. Provide informed consent signed by study patient
8. Able to understand and complete study-related questionnaires
Exclusion Criteria
Exclusion Criteria
A patient who meets any of the following criteria will be excluded from the study:
1. 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)
2. History of bone marrow transplantation
3. Body weight < 40 kilograms at screening visit
4. Planned modification (initiation, discontinuation, or dose / dosing interval change) to the
following background concomitant medications, as applicable, during screening and
treatment periods: erythropoietin, immunosuppressive drugs, corticosteroids,
anti-thrombotic agents, anticoagulants, iron supplements, and folic acid
5. Peripheral blood absolute neutrophil count (ANC) <500/μL [<1.0 x 109
/L] or peripheral
blood platelet count <50,000/μL
6. No documented meningococcal vaccination within 3 years prior to screening and patient
unwillingness to undergo vaccination during the study
7. Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of
active or latent tuberculosis infection (LTBI) during screening period. Assessment for
active TB and LTBI should accord with local practice or guidelines, including those
pertaining to risk assessment, and the use of tuberculin skin test or T-cell interferongamma release assay
8. Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic
prophylaxis therapy as recommended in the study
9. Any active, ongoing infection within 2 weeks of screening or during the screening period
10. A recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or
antifungals within 2 weeks of screening or during the screening period
11. Immunization with a live-attenuated vaccine 1 month prior to REGN3918 administration
12. Known hereditary complement deficiency
13. Documented history of active, ongoing systemic autoimmune diseases
14. Documented history of liver cirrhosis, or patients with liver disease unrelated to PNH
with ALT or AST greater than 3× ULN at the screening visit
15. Patients with an eGFR of < 30 mL/min/1.73m2
(according to Chronic Kidney
Disease - Epidemiology Collaboration equation 2009) at screening visit
16. Recent, unstable medical conditions, excluding PNH and PNH-related complications,
within the past 3 months prior to screening visit (eg, myocardial infarction, congestive
heart failure with New York Heart Association Class ≥ III, serious uncontrolled cardiac
arrhythmia, cerebrovascular accident, active gastrointestinal bleed)
17. Anticipated need for major surgery during the study
18. Coexisting, chronic anemia unrelated to PNH
19. History of cancer within the past 5 years, except for adequately treated basal cell skin
cancer, squamous cell skin cancer, or in situ cervical cancer
20. Participation in another interventional clinical study or use of any experimental therapy
within 30 days before screening visit or within 5 half-lives of that investigational product,
whichever is greater, with the exception of complement inhibitors (see Section 6.2.1)
21. Known sensitivity to doxycycline or to any of the components of the REGN3918
formulation and drug product
22. History of significant multiple and/or severe allergies (including latex gloves) or has had
an anaphylactic reaction or significant intolerability to prescription or nonprescription
drugs
23. 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
24. Considered by the Investigator or any sub-Investigator as inappropriate for this study for
any reason, eg:
Deemed unable to meet specific protocol requirements, such as scheduled visits
Deemed unable to tolerate long-term injections as per the patient, the investigator,
sub-Investigator, pharmacist, study coordinator, other study staff, or relative thereof
directly involved in the conduct of the protocol, etc.
Presence of any other conditions (eg, geographic, social, etc), actual or anticipated,
that the investigator feels would restrict or limit the patient’s participation for the
duration of the study
25. Women who are pregnant, breastfeeding, or who have a positive pregnancy test at
screening visit or day 1
26. Patients who are committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities
27. Pregnant or breastfeeding women
28. Women of childbearing potential* who are unwilling to practice highly effective
contraception prior to the initial dose/start of the first treatment, during the study, and for
at least 21 weeks after the last dose. Highly effective contraceptive measures include:
a. stable use of combined (estrogen and progestogen-containing) hormonal
contraception (oral, intravaginal, transdermal) or progestogen-only hormonal
contraception (oral, injectable, implantable) associated with inhibition of ovulation
initiated 2 or more menstrual cycles prior to screening
b. intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
c. bilateral tubal ligation
d. vasectomized partner
e. and/or sexual abstinence†, ‡.
29. Known chronic infection with hepatitis B or C, defined as a testing history showing a
currently positive status for hepatitis B surface antigen (HBsAg), hepatitis B e antigen
(HBeAg), hepatitis B virus DNA, or hepatitis C virus RNA (HCV RNA).
A patient who meets any of the following criteria will be excluded from the study:
1. 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)
2. History of bone marrow transplantation
3. Body weight < 40 kilograms at screening visit
4. Planned modification (initiation, discontinuation, or dose / dosing interval change) to the
following background concomitant medications, as applicable, during screening and
treatment periods: erythropoietin, immunosuppressive drugs, corticosteroids,
anti-thrombotic agents, anticoagulants, iron supplements, and folic acid
5. Peripheral blood absolute neutrophil count (ANC) <500/μL [<1.0 x 109
/L] or peripheral
blood platelet count <50,000/μL
6. No documented meningococcal vaccination within 3 years prior to screening and patient
unwillingness to undergo vaccination during the study
7. Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of
active or latent tuberculosis infection (LTBI) during screening period. Assessment for
active TB and LTBI should accord with local practice or guidelines, including those
pertaining to risk assessment, and the use of tuberculin skin test or T-cell interferongamma release assay
8. Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic
prophylaxis therapy as recommended in the study
9. Any active, ongoing infection within 2 weeks of screening or during the screening period
10. A recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or
antifungals within 2 weeks of screening or during the screening period
11. Immunization with a live-attenuated vaccine 1 month prior to REGN3918 administration
12. Known hereditary complement deficiency
13. Documented history of active, ongoing systemic autoimmune diseases
14. Documented history of liver cirrhosis, or patients with liver disease unrelated to PNH
with ALT or AST greater than 3× ULN at the screening visit
15. Patients with an eGFR of < 30 mL/min/1.73m2
(according to Chronic Kidney
Disease - Epidemiology Collaboration equation 2009) at screening visit
16. Recent, unstable medical conditions, excluding PNH and PNH-related complications,
within the past 3 months prior to screening visit (eg, myocardial infarction, congestive
heart failure with New York Heart Association Class ≥ III, serious uncontrolled cardiac
arrhythmia, cerebrovascular accident, active gastrointestinal bleed)
17. Anticipated need for major surgery during the study
18. Coexisting, chronic anemia unrelated to PNH
19. History of cancer within the past 5 years, except for adequately treated basal cell skin
cancer, squamous cell skin cancer, or in situ cervical cancer
20. Participation in another interventional clinical study or use of any experimental therapy
within 30 days before screening visit or within 5 half-lives of that investigational product,
whichever is greater, with the exception of complement inhibitors (see Section 6.2.1)
21. Known sensitivity to doxycycline or to any of the components of the REGN3918
formulation and drug product
22. History of significant multiple and/or severe allergies (including latex gloves) or has had
an anaphylactic reaction or significant intolerability to prescription or nonprescription
drugs
23. 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
24. Considered by the Investigator or any sub-Investigator as inappropriate for this study for
any reason, eg:
Deemed unable to meet specific protocol requirements, such as scheduled visits
Deemed unable to tolerate long-term injections as per the patient, the investigator,
sub-Investigator, pharmacist, study coordinator, other study staff, or relative thereof
directly involved in the conduct of the protocol, etc.
Presence of any other conditions (eg, geographic, social, etc), actual or anticipated,
that the investigator feels would restrict or limit the patient’s participation for the
duration of the study
25. Women who are pregnant, breastfeeding, or who have a positive pregnancy test at
screening visit or day 1
26. Patients who are committed to an institution by virtue of an order issued either by the
judicial or the administrative authorities
27. Pregnant or breastfeeding women
28. Women of childbearing potential* who are unwilling to practice highly effective
contraception prior to the initial dose/start of the first treatment, during the study, and for
at least 21 weeks after the last dose. Highly effective contraceptive measures include:
a. stable use of combined (estrogen and progestogen-containing) hormonal
contraception (oral, intravaginal, transdermal) or progestogen-only hormonal
contraception (oral, injectable, implantable) associated with inhibition of ovulation
initiated 2 or more menstrual cycles prior to screening
b. intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
c. bilateral tubal ligation
d. vasectomized partner
e. and/or sexual abstinence†, ‡.
29. Known chronic infection with hepatitis B or C, defined as a testing history showing a
currently positive status for hepatitis B surface antigen (HBsAg), hepatitis B e antigen
(HBeAg), hepatitis B virus DNA, or hepatitis C virus RNA (HCV RNA).
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
42 participants
