A trial with REGN3918 in patients Paroxysmal Nocturnal Hemoglobinuria (PNH) who have not been treated previously with a Complement Inhibitor or Have Not Recently Received Complement Inhibitor Therapy

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2018-002734-20-NL
• Date of registration: 02/04/2019
• Prospective Registration: Yes
• Primary sponsor: Regeneron Pharmaceuticals, Inc.
• Public title: A trial with REGN3918 in patients Paroxysmal Nocturnal Hemoglobinuria (PNH) who have not been treated previously with a Complement Inhibitor or Have Not Recently Received Complement Inhibitor Therapy
• Scientific 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
• Date of first enrolment: 29/07/2019
• Target sample size: 42
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002734-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Czech Republic, Germany, Hong Kong, Hungary, Italy, Korea, Democratic People's Republic of, Malaysia, Netherlands, Poland, Romania, Singapore, South Africa, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

• Name: Clinical Trial Information
• Affiliation: Regeneron Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female = 18 years of age or legal age of majority at screening, whichever is greater
•Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high sensitivity flow cytometry
•Active disease, as defined by the presence of 1 or more PNH related signs or symptoms 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.
•PNH granulocytes (denoted as polymorphonuclear [PMN]) >10% at screening visit.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 12

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)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal nocturnal hemoglobinuria
MedDRA version: 21.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: REGN3918
Product Code: REGN3918
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: REGN3918
Current Sponsor code: REGN3918
Other descriptive name: REGN3918
Concentration unit: mg/g milligram(s)/gram
Concentration type: up to
Concentration number: 265-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 26 weeks

Main Objective: 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

Primary end point(s): The co primary endpoints are:
•The proportion of patients achieving adequate control of their intravascular hemolysis, defined as LDH = 1.5 x ULN at every scheduled time point between week 4 and week 26, inclusive
•The proportion of patients achieving transfusion avoidance defined as no post baseline transfusion of RBCs per protocol over 26 weeks

Secondary Objective: 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.
•To evaluate the effect of REGN3918 on patient reported outcomes (PROs) measuring fatigue and health related quality of life

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints include:
•The rate of breakthrough hemolysis over 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 (ie, LDH = 1.5 x ULN)
•The proportion of patients achieving normalization of their intravascular hemolysis, defined as LDH = 1.0 x ULN at every scheduled time point between week 4 through week 26, inclusive
•Time to first LDH = 1.5 x ULN
•Percentage of days with LDH = 1.5 x ULN between week 4 and week 26, inclusive.
•Change and percent change in LDH levels from baseline to week 26

Timepoint(s) of evaluation of this end point: 26 weeks

Secondary ID(s)

2018-002734-20-CZ

R3918-PNH-1852

Source(s) of Monetary Support

Regeneron Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 29/07/2019
Contact: