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Trial registered on ANZCTR


Registration number
ACTRN12617000023358
Ethics application status
Approved
Date submitted
13/12/2016
Date registered
9/01/2017
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Screening Study in Patients with Untreated Paroxysmal Nocturnal Hemoglobinuria
Scientific title
A Screening Study for the ACH471-100 Treatment Study in Patients with Untreated Paroxysmal Nocturnal Hemoglobinuria
Secondary ID [1] 290100 0
None
Universal Trial Number (UTN)
U1111-1187-2875
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria 300190 0
Condition category
Condition code
Inflammatory and Immune System 300074 300074 0 0
Autoimmune diseases
Blood 301143 301143 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 295843 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299544 0
To determine baseline characteristics in patients with paroxysmal nocturnal hemoglobinuria (PNH) who are not currently receiving eculizumab, including:
*Transfusion history via patient interview
Timepoint [1] 299544 0
Visit 1 and every 2 weeks thereafter until study completion. There is no specific length of time that the patients will participate in this screening study. It is anticipated that most patients will be in this screening study for 2 or 3 months
Primary outcome [2] 300546 0
To determine baseline characteristics in patients with paroxysmal nocturnal hemoglobinuria (PNH) who are not currently receiving eculizumab, including:
Lactate dehydrogenase (LDH) plasma concentrations, measured by blood test
Timepoint [2] 300546 0
Visit 1 and every 2 weeks thereafter until study completion. There is no specific length of time that the patients will participate in this screening study. It is anticipated that most patients will be in this screening study for 2 or 3 months
Primary outcome [3] 300631 0
To determine baseline characteristics in patients with paroxysmal nocturnal hemoglobinuria (PNH) who are not currently receiving eculizumab, including:
hemoglobin (Hgb) plasma concentrations, measured by blood test
Timepoint [3] 300631 0
Visit 1 and every 2 weeks thereafter until study completion. There is no specific length of time that the patients will participate in this screening study. It is anticipated that most patients will be in this screening study for 2 or 3 months
Secondary outcome [1] 327488 0
To gather information about the patients’ experience of their disease, by patient interview and quality of life questionnaires (i.e. FACIT and EORTC QLQ-C30)
Timepoint [1] 327488 0
Visit 1 and every 4 weeks thereafter until study completion (patient interview will only occur once during the study). There is no specific length of time that the patients will participate in this screening study. It is anticipated that most patients will be in this screening study for 2 or 3 months
Secondary outcome [2] 330459 0
To gather information about the patients’ disease impact on their everyday lives, by patient interview and quality of life questionnaires (i.e. FACIT and EORTC QLQ-C30)
Timepoint [2] 330459 0
Visit 1 and every 4 weeks thereafter until study completion (patient interview will only occur once during the study). There is no specific length of time that the patients will participate in this screening study. It is anticipated that most patients will be in this screening study for 2 or 3 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/01/2017
Actual
16/02/2017
Date of last participant enrolment
Anticipated
Actual
21/02/2017
Date of last data collection
Anticipated
Actual
30/11/2017
Sample size
Target
8
Accrual to date
Final
2
Recruitment outside Australia
Country [1] 8202 0
New Zealand
State/province [1] 8202 0

Funding & Sponsors
Funding source category [1] 294469 0
Commercial sector/Industry
Name [1] 294469 0
Achillion Pharmaceuticals, Inc.
Country [1] 294469 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Achillion Pharmaceuticals, Inc.
Address
300 George Street
New Haven, CT 06511
Country
United States of America
Secondary sponsor category [1] 293335 0
Commercial sector/Industry
Name [1] 293335 0
Clinical Network Services (CNS) Ltd
Address [1] 293335 0
PO Box 78312
Grey Lynn
Auckland 1245
Country [1] 293335 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295906 0
The Central Health and Disability Ethics Committee
Ethics committee address [1] 295906 0
Ethics committee country [1] 295906 0
New Zealand
Date submitted for ethics approval [1] 295906 0
11/08/2016
Approval date [1] 295906 0
02/09/2016
Ethics approval number [1] 295906 0
16/CEN/122

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68850 0
Prof Peter Browett
Address 68850 0
Auckland Clinical Studies Ltd
Ground Floor
MEDACS House
3 Ferncroft Street
Auckland 1010
Country 68850 0
New Zealand
Phone 68850 0
+6493733474
Fax 68850 0
Email 68850 0
[email protected]
Contact person for public queries
Name 68851 0
Glenn Schulman
Address 68851 0
Achillion Pharmaceuticals, Inc.
300 George Street
New Haven, CT 06511
Country 68851 0
United States of America
Phone 68851 0
+12037525510
Fax 68851 0
Email 68851 0
[email protected]
Contact person for scientific queries
Name 68852 0
Peter Browett
Address 68852 0
Auckland Clinical Studies Ltd
Ground Floor
MEDACS House
3 Ferncroft Street
Auckland 1010
Country 68852 0
New Zealand
Phone 68852 0
+6493733474
Fax 68852 0
Email 68852 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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