This trial is designed to determine what effects the investigational medicine, ABP 959, has on the human body, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, eculizumab, in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). This study will assess if the investigational medicine is safe and effective in treating PNH compared to the licensed medicine.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2017-001418-27-GB
• Date of registration: 11/12/2018
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc.
• Public title: This trial is designed to determine what effects the investigational medicine, ABP 959, has on the human body, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, eculizumab, in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). This study will assess if the investigational medicine is safe and effective in treating PNH compared to the licensed medicine.
• Scientific 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) - ABP 959 in PNH
• Date of first enrolment: 14/12/2018
• Target sample size: 40
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001418-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, Netherlands, Norway, Spain, United Kingdom

Contacts

• Name: IHQ Medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ Medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
The study will enroll participants with PNH who are stable on eculizumab treatment. All inclusion criteria must be met.
1. Men and women = 18 years of age
2. Historical diagnosis of PNH by documented flow cytometry (e.g., type III erythrocyte cells of = 10%)
3. Administration of eculizumab for = 6 months and currently receiving 900 mg of eculizumab every 14 ± 2 days
4. Haemoglobin = 9.0 g/dL for at least 6 weeks prior to randomisation
5. Lactate dehydrogenase (LDH) < 1.5 × the upper limit of normal at screening
6. Platelet count = 50 × 1 09/L
7. Absolute neutrophil (a type of white blood cell) count = 0.5 x 1 09/L (500/µL)
8. Participants must have been vaccinated against Neisseria meningitidis (meningococcus – a bacteria which causes meningitis). Participants must be vaccinated or revaccinated according to current national guidelines for vaccination use.
9. Participants must sign an independent ethics committee-approved informed consent form before participation in any procedures.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
If any of the following apply, the subject MUST NOT enter the study:
1. Known or suspected hereditary complement deficiency
2. Clinically significant cardiovascular disease (including myocardial infarction (heart attack), unstable angina, symptomatic congestive heart failure [New York Heart Association = Class III], serious uncontrolled cardiac arrhythmia), peripheral vascular disease (a blood circulation disorder), cerebrovascular accident (stroke), or transient ischemic attack (mini stroke) in the previous 6 months
3. Evidence of acute thrombosis (liver Doppler ultrasound of hepatic and portal veins)
4. Known to be positive for human immunodeficiency virus (HIV)
5. Women who are pregnant or breastfeeding
6. Women of childbearing potential who does not consent to use a highly effective method of birth control (eg, true abstinence, sterilisation, birth control pills, Depo Provera injections, or contraceptive implants) during treatment and for an additional 5 months after the last administration of protocol-specified treatment
WOCBP is defined as a woman who is fertile, following menarche, and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral
oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT).
However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Females on HRT and whose menopausal status is in doubt will be required to use 1 of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.
7. Males with partners of childbearing potential who do not consent to use a highly effective method of birth control (eg, true abstinence, vasectomy, or a condom in combination with hormonal birth control or barrier methods used by the woman) during treatment and for an additional 5 months after the last administration of protocol-specified treatment
8. Participant is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or the participant is receiving other investigational agent(s).
9. Particpant has known sensitivity to any constituent of the products to be administered during the study, including mammalian cell-derived products.
10. History or evidence of clinically significant disorder, infection, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
11. History of meningococcal infection
12. Presence or suspicion of active bacterial infection, or recurrent bacterial infection
13. History of bone marrow transplantation
14. Red blood cell transfusion required within

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

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 20.1 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: ABP 959
Product Code: ABP 959
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Current Sponsor code: ABP 959
Other descriptive name: ABP 959 - biosimilar to eculizumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 900-

Trade Name: Soliris
Product Name: Soliris
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ECULIZUMAB
CAS Number: 219685-50-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 900-

Primary Outcome(s)

Primary end point(s): Primary Endpoint for Parallel Comparison:
• Haemolysis, as measured by LDH at week 27
Primary Endpoint for Crossover Comparison:
• Haemolysis, as measured by the time-adjusted AUEC of LDH from week 39 to 53 and from week 65 to 79

Timepoint(s) of evaluation of this end point: The primary analysis of the primary endpoint of week 27 LDH for the parallel comparison will be conducted on the Full Analysis Set (FAS), consisting of all randomized subjects, with treatment as randomized in Period 1 regardless of treatment actually received.
The primary analysis of the primary endpoint of time-adjusted AUEC of LDH for the crossover comparison will be conducted on the Modified Full Analysis Set (mFAS), consisting of all randomized subjects who have an LDH-time profile evaluable for the time-adjusted AUEC within weeks 39 to 53 and/or within weeks 65 to 79, according to treatment per the randomized sequence regardless of treatment actually received.

Secondary Objective: The secondary objectives are to assess the safety, pharmacokinetics (PK) (how the body processes the medication) and immunogenicity (whether the body produces an immune response) of ABP 959 compared with eculizumab.

Main Objective: The primary objective for this study is to evaluate the efficacy of ABP 959 compared with eculizumab based on control of intravascular haemolysis (the breakdown of red blood cells in blood vessels).

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The analysis of secondary endpoints (except for PK) will be conducted on the FAS. Total complement, total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of hemoglobinuria, and type III erythrocytes (%) at weeks 27, 39, 53, 65, and 79 will be summarized descriptively. For the endpoint of RBC transfusions, summary statistics for the number of packed red cells transfused per month after week 13 will be presented. A descriptive summary of LDH at each time point through the end of the study (EOS) visit will be presented. Individual and mean LDH-time profile through EOS visit will also be presented graphically.
The secondary endpoint of crossover comparison of LDH at week 53 and week 79 will be evaluated descriptively.

Secondary end point(s): • Total complement (CH50), total hemoglobin, serum-free hemoglobin, haptoglobin, bilirubin, degree of hemoglobinuria, and type III erythrocytes at week 27, week 39, week 53, and post-crossover week 65 and week 79
• Crossover comparison of hemolysis as measured by LDH at week 53 and week 79
• Lactate dehydrogenase-time profile
• Red blood cell transfusion
• Pharmacokinetic area under the curve (AUC) of ABP 959 and eculizumab from week 13 to 15, and trough PK

Secondary ID(s)

20150168

2017-001418-27-DE

Source(s) of Monetary Support

Amgen Inc.

Ethics review

Status: Approved
Approval date:
Contact: