A Clinical Study with Investigational Drug, ALN-CC5, in patients with Paroxysmal Nocturnal Hemoglobinuria who are Inadequate Responders to Eculizumab

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2016-002943-40-ES
• Date of registration: 30/09/2016
• Prospective Registration: Yes
• Primary sponsor: Alnylam Pharmaceuticals Inc
• Public title: A Clinical Study with Investigational Drug, ALN-CC5, in patients with Paroxysmal Nocturnal Hemoglobinuria who are Inadequate Responders to Eculizumab
• Scientific title: A Phase 2, Open-label, Single Dose, Study of Subcutaneously Administered ALN-CC5 in Patients with Paroxysmal Nocturnal Hemoglobinuria who are Inadequate Responders to Eculizumab
• Date of first enrolment: 21/11/2016
• Target sample size: 15
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002943-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Israel, Korea, Republic of, Netherlands, Norway, Russian Federation, Spain, Sweden, Taiwan, Turkey, United Kingdom

Contacts

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

• Name: Clinical Trials Hotline
• Affiliation: Alnylam Pharmaceuticals Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 18 years or older
2. History of PNH
3. Treatment with eculizumab at a stable dose for a minimum of 60 days before Screening
4. Inadequate response to eculizumab as defined by elevated LDH level before eculizumab infusion at Screening as follows:
• LDH=3.0×ULN (with or without symptoms) attributable to hemolysis in the opinion of the Investigator; or,
• LDH =2.0×ULN, 1 or more of the following at Screening and while receiving eculizumab treatment, and which in the opinion of the Investigator is/are attributable to PNH disease: PNH symptoms (eg, fatigue, abdominal pain, dyspnea, dysphagia, or erectile dysfunction); Hemoglobin level =10 g/dL; Any blood transfusions within 90 days before Screening; and/or Spontaneous vascular thrombosis at any time since starting eculizumab treatment.
5. Women of child-bearing potential (WOCBP) must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception 14 days before ALN-CC5 administration, throughout study participation, and for 6 months after ALN-CC5 administration.
6. Willing and able to comply with the study requirements and to provide written informed consent
7. Vaccinated against Neisseria meningitides according to standard practice (patients may be rescreened if not previously vaccinated)
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 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Alanine transaminase =2×ULN or total bilirubin =4×ULN (unless bilirubin elevation is due to Gilbert’s syndrome), which is considered clinically relevant in the opinion of the Investigator
2. Clinically significant bone marrow suppression as defined by 2 or more of the following:
• Absolute neutrophil count =1.0×10 to power of 9/L
• Platelet count =50×10 to power of 9/L
• Absolute reticulocyte count =60×10 to power of 9/L
3. Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator
4. Planned change in eculizumab dose within 60 days of administration of ALN-CC5 (patients may be re-Screened)
5. Spontaneous vascular thrombosis within 30 days of randomization (patients may be re Screened)
6. Known or suspected hereditary asymptomatic complement deficiency
7. Known clinical laboratory evidence or clinical diagnosis of human immunodeficiency virus infection (HIV), hepatitis C virus (HCV) infection, or chronic hepatitis B virus infection as shown by hepatitis B surface antigen positivity in blood
8. Suspicion of active viral, bacterial, fungal, or parasitic infection as a cause for breakthrough hemolysis and their presence within 14 days before ALN-CC5 administration (patients may be rescreened)
9. Travelled to Saudi Arabia or Africa within 90 days of Screening, or planning to do so during the study (patients may be rescreened)
10. Received an investigational agent within the last 90 days or are in follow-up of another clinical study before study enrollment
11. Active serious mental illness or psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention
12. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
13. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc
14. History of intolerance to SC injection(s) at the proposed injection site(s) that could potentially hinder study drug administration or evaluation of local tolerability
15. History of meningococcal infection within 12 months before Screening
16. Known history of chronic liver disease or cirrhosis


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

Health Condition(s) or Problem(s) studied

Paroxysmal nocturnal hemoglobinuria (PNH)
MedDRA version: 19.0 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 Code: ALN-CC5
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-62643
Current Sponsor code: ALN-62643
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At Week 12

Main Objective: Evaluate the effect of ALN-CC5 on red blood cell (RBC) hemolysis

Primary end point(s): Percent change from baseline in LDH

Secondary Objective: Evaluate the safety and tolerability of ALN-CC5
Characterize the pharmacodynamic (PD) effect of ALN-CC5

Secondary Outcome(s)

Secondary end point(s): • Incidence of AEs
• Proportion of patients with LDH levels =1.5×ULN
• Change in complement activity levels (CAP and CCP)

Timepoint(s) of evaluation of this end point: • Incidence of AEs: throughout the study until the end of study visit
• Proportion of patients with LDH levels =1.5×ULN: at Week 12
• Change in complement activity levels (CAP and CCP): throughout the study until the end of study visit

Secondary ID(s)

ALN-CC5-003

Source(s) of Monetary Support

Alnylam Pharmaceuticals Inc