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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03053102




Registration number
NCT03053102
Ethics application status
Date submitted
1/02/2017
Date registered
14/02/2017
Date last updated
23/06/2022

Titles & IDs
Public title
Study of Danicopan in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Scientific title
A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of ACH-0144471 in Untreated Patients With Paroxysmal Nocturnal Hemoglobinuria
Secondary ID [1] 0 0
2016-002652-25
Secondary ID [2] 0 0
ACH471-100
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria (PNH) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Danicopan

Experimental: Danicopan - Starting doses of danicopan ranged from 100 to 150 milligrams (mg) three times daily (TID), with subsequent dose escalation up to 200 mg TID based on response (clinical and biochemical) for 28 days (Part 1). Participants with reductions in lactate dehydrogenase (LDH) meeting specified criteria were offered continued dosing beyond Day 28, for up to 8 additional weeks (Part 2).


Treatment: Drugs: Danicopan
Danicopan was administered as multiple oral doses over a period of at least 28 days.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline In Serum LDH Levels At Day 28
Timepoint [1] 0 0
Baseline, Day 28
Secondary outcome [1] 0 0
Change From Baseline In Hemoglobin (Hgb) At Days 28 And 84
Timepoint [1] 0 0
Baseline, Days 28 and 84
Secondary outcome [2] 0 0
Change From Baseline In Serum LDH Levels At Day 84
Timepoint [2] 0 0
Baseline, Day 84
Secondary outcome [3] 0 0
Paroxysmal Nocturnal Hemoglobinuria (PNH) Type III Red Blood Cell (RBC) Clone Size
Timepoint [3] 0 0
Baseline, Day 28, and Day 84
Secondary outcome [4] 0 0
Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation
Timepoint [4] 0 0
After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104)
Secondary outcome [5] 0 0
Grade 3 And Grade 4 Laboratory Abnormalities
Timepoint [5] 0 0
After the first dose of study medication (Day 1) through 14 days after the last dose of study drug (up to Day 104).
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Post-dose (AUC0-8)
Timepoint [6] 0 0
Days 6 and 20
Secondary outcome [7] 0 0
PK: Maximum Plasma Concentration (Cmax)
Timepoint [7] 0 0
Days 6 and 20
Secondary outcome [8] 0 0
PK: Time To Maximum Concentration (Tmax)
Timepoint [8] 0 0
Days 6 and 20
Secondary outcome [9] 0 0
Complement Alternative Pathway (AP) Functional Activity
Timepoint [9] 0 0
Baseline and Day 28
Secondary outcome [10] 0 0
Complement Bb
Timepoint [10] 0 0
Baseline and Day 28

Eligibility
Key inclusion criteria
* Currently untreated PNH participants with PNH Type III erythrocyte and/or granulocyte clone size =10% and anemia (hemoglobin <12 grams/deciliter) with adequate reticulocytosis (as determined by the Investigator).
* LDH =1.5 x the upper limit of normal.
* Platelets =50,000/microliter without the need for platelet transfusions.
* Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae, or willingness to receive vaccinations during the screening period.
* Negative pregnancy test for females prior to dosing and throughout the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
* Participants who had received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater.
* Participants who had received eculizumab at any dose or interval within the past 75 days before study entry.
* Participants with known or suspected complement deficiency.
* Participants with active bacterial infection or clinically significant active viral infection, a body temperature >38°Celsius, or other evidence of infection on Day 1, or with a history of febrile illness within 14 days prior to first study drug administration.
* History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection.
* Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Italy
State/province [1] 0 0
Florence
Country [2] 0 0
Italy
State/province [2] 0 0
Naples
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Seoul
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auckland
Country [5] 0 0
United Kingdom
State/province [5] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Achillion, a wholly owned subsidiary of Alexion
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski... [More Details]