None listed
Conditions
Brief summary
This is a multiple-center screening study designed to obtain baseline information before a patient enters into the Achillion treatment Study ACH471–100. Patients will be evaluated over time to evaluate transfusion history, levels of ongoing hemolysis (i.e., LDH and Hgb), and Quality of Life (QoL) assessments to establish a baseline. Patients will have an initial visit and procedures to confirm their eligibility for this study and, subsequently, the ACH471-100 treatment study. In addition, the status of their vaccinations against N. meningitidis (quadrivalent ACWY and serogroup B), H. influenzae, and S. pneumoniae will be determined. Once entered into this screening study, patients will be evaluated every 4 weeks (+/- 3 days) by the Principal Investigator (PI). In addition, patients will have LDH and Hgb measured every 2 weeks (+/- 3 days) following their visit to the investigational site; these laboratory tests can be drawn either at the investigational site or at a laboratory local to the patient.. The Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT) Fatigue Scale (Version 4) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaires will be administered to patients during this study to collect baseline health-related QoL information. In addition, patients will be interviewed by an independent outcomes researcher selected by the Sponsor once during the study to collect their experience of PNH, its impact on everyday lives and the disease trajectory. Interviews will be conducted over the phone by a trained, experienced interviewer and will last approximately 30 minutes. Patients who have not been vaccinated against N. meningitidis, H. influenzae, and S. pneumoniae will receive vaccinations and patients who have been previously vaccinated will receive recommended boosters during this study.
Interventions
The study is a pre-screening study.
Patients will be evaluated over time to evaluate transfusion history, levels of ongoing hemolysis (i.e., LDH and Hgb), and Quality of Life (QoL) assessments to establish a baseline.
In addition, patients will be interviewed one time during the study by an independent outcomes researcher to collect their experience of PNH, its impact on everyday lives and the disease trajectory. Although no exact timing has been specified, this single interview will be complete
The study is a pre-screening study. Patients will be evaluated over time to evaluate transfusion history, levels of ongoing hemolysis (i.e., LDH and Hgb), and Quality of Life (QoL) assessments to establish a baseline. In addition, patients will be interviewed one time during the study by an independent outcomes researcher to collect their experience of PNH, its impact on everyday lives and the disease trajectory. Although no exact timing has been specified, this single interview will be completed once the patient is entered into the study. Patients who have not been vaccinated against N. meningitidis, H. influenzae, and S. pneumoniae will receive vaccinations and patients who have been previously vaccinated will receive recommended boosters during this study. Patients will be evaluated every 2 weeks during this study until entry into the ACH471-100 treatment study. There is no specific length of time that the patients will participate in this screening study. It is expected patients who are willing and eligible to participate in the ACH471-100 Treatment Study to enrol once the treatment study becomes operational in the first half of 2017 and any required vaccinations have been completed. It is anticipated that most patients will be in this screening study for 2 or 3 months. Any patients who do not have a sufficient vaccination history will receive vaccines during this study against N. meningitidis serogroups A, C, Y and W135, N. meningitidis serogroup B, S. pneumoniae, and H. influenza (per the respective marketed product information). The ACH471-100 Treatment Study is expected to commence during the first half of 2017.
Sponsors
Achillion Pharmaceuticals, Inc.
Study design
Allocation
Non-randomised trial
Primary purpose
Diagnosis
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Currently untreated PNH with PNH Type III erythrocyte and/or granulocyte clone size greater than or equal to 10% and anemia (hemoglobin <12 g/dL) with adequate reticulocytosis (as determined by the Investigator) 2. LDH greater than or equal to 1.5× upper limit of normal (ULN) 3. Platelets greater than or equal to 50,000/micro L without the need for platelet transfusions 4. Documentation of vaccination for N. meningitidis (quadrivalent ACWY and serogroup B) within 6 months before entering study ACH471-100, or willingness to receive these vaccinations during this study 5. Documentation of vaccination against H. influenzae and S. pneumoniae at any time before entering this study, or willingness to receive these vaccinations during this study 6. Age 18 years or older 7. Female patients must be of non-childbearing potential or must agree to abstinence or to the use of an effective form of contraception when engaged in sexual activity. Female patients of childbearing potential must have a negative serum pregnancy test at the Eligibility Visit and a negative urine pregnancy test on Day 1. 8. Male patients must be willing to agree to abstinence or to the use of an effective form of contraception when engaged in sexual activity once enrolled in Study ACH471-100. 9. Patients must agree to provide written informed consent
Exclusion criteria
1. History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant 2. Patients who will have received another investigational agent within 30 days or 5 half-lives of the investigational agent, whichever is greater, before Day 1 of Study ACH471-100. 3. Patients who will have received eculizumab at any dose or interval within the past 75 days before Day 1 of Study ACH471-100 4. Patients with known or suspected complement deficiency 5. History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection 6. History of hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems, which in the opinion of the Investigator would make it difficult to properly provide either empiric antibiotic therapy or treat an active infection 7. History or presence of any clinically relevant co-morbidities that, in the opinion of the PI, would make the patient inappropriate for the study (for example, is likely to result in deterioration of the patient’s condition, affect the patient’s safety during the study, or confound the results of the study) 8. Laboratory abnormalities at screening, including: * Alkaline phosphatase > ULN * Absolute neutrophil counts <1,000/micro L * Alanine aminotransferase (ALT) > ULN * Aspartate aminotransferase (AST) > ULN * Any other clinically significant laboratory abnormality that, in the opinion of the PI, would make the patient inappropriate for the study or put the patient at undue risk 9. Females of childbearing potential who have a positive serum pregnancy (human chorionic gonadotropin [HCG]) test at the Eligibility visit, or nursing mothers 10. Prior history or current evidence of biliary cholestasis 11. Patients diagnosed with Gilbert’s syndrome. Patients with history or family history suggestive of Gilbert’s syndrome should be tested and excluded from study if positive for UGT1A1 genotyping polymorphism or missense change. 12. Patients with evidence of HIV, hepatitis B or hepatitis C infection (positive serology for HIV-1, positive hepatitis B surface antigen, or positive anti-HCV antibody at Screening or historically)
Outcome results
None listed