DANICOPAN for Paroxysmal nocturnal hemoglobinuria

Inclusion criteria

• {"criterion_text":"- 1. 12 to < 18 years of age at the time of signing the informed consent."}
• {"criterion_text":"- 10. The Investigator, or a person designated by the Investigator, will obtain written informed consent from each study participant’s legal guardian/LAR (as defined in Section 10) and the participant’s assent, when applicable, before any study-specific activity is performed. All legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand."}
• {"criterion_text":"- 11. Participant’s legal guardian/LAR must be willing and able to give written informed consent and the participant must be willing to give written informed assent (if determined applicable by the IRB or EC) and comply with the study visit schedule."}
• {"criterion_text":"- 12. A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day according to the SoA (eg, able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed."}
• {"criterion_text":"- 13. A legal guardian or primary caregiver must be able to accurately maintain the child’s take-home record, including items of general health."}
• {"criterion_text":"- 14. Must have access to emergency medical care."}
• {"criterion_text":"- 2. Confirmed diagnosis of PNH."}
• {"criterion_text":"- 3. CS-EVH defined by: − Anemia: Hgb ≤ 11 g/dL, and − Absolute reticulocyte count ≥ 100 × 10^9/L"}
• {"criterion_text":"- 4. Treated with ravulizumab or eculizumab for at least 12 weeks immediately preceding Day 1, the dose received should be stable during this period, and there should be no anticipated changes in dosage or interval during the first 12 weeks of this study."}
• {"criterion_text":"- 5. Body weight > 25 kg."}
• {"criterion_text":"- 6. To reduce the risk of meningococcal infection (N meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, W, and Y and serogroup B within 3 years prior to, or at least 14 days prior to Day 1 according to national/local guidelines. Participants who do not meet this requirement will be vaccinated against meningococcal infection according to national/local guidelines and will receive prophylactic antibiotics for at least 2 weeks after meningococcal vaccination if Day 1 occurs < 2 weeks after initial vaccination."}
• {"criterion_text":"- 7. Have been vaccinated against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae according to national and local vaccination schedule guidelines (Section 6.8.4)."}
• {"criterion_text":"- 8. Male or female."}
• {"criterion_text":"- 9. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (Section 10.5). Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a WONCBP as defined in Section 10.5 Contraceptive and Barrier Guidance. • Is a WOCBP and using a required contraceptive method as described in Section 10.5 (from informed consent signing until 3 days after the last dose of danicopan). The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. • A WOCBP must have a negative serum pregnancy test (Screening) and urine pregnancy test (Day 1). If the urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. WOCBP must agree to use an effective or highly effective method of contraception (see Section 10.5) from the date of signing the informed consent to 3 days after their last dose of danicopan if they are of childbearing potential (ie, have achieved menarche) or become of childbearing potential during the study. Contraceptive and barrier use as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric participants and as required by local regulations. Note: If the childbearing potential changes after start of the study (eg, a premenarchal female participant experiences menarche) or the risk of pregnancy changes (eg, a female participant who is not heterosexually active becomes active), the participant must discuss these changes with the Investigator who then should determine if a female participant must begin a highly effective method of contraception or a male participant must use a condom. If reproductive status is questionable, additional evaluation should be considered."}

Exclusion criteria

• {"criterion_text":"- 1. Platelet count < 30000/μL or there is a need for platelet transfusions."}
• {"criterion_text":"- 10. Any other clinically significant laboratory abnormality, in the opinion of the Investigator, makes the participant inappropriate for the study or puts the participant at undue risk."}
• {"criterion_text":"- 11. Currently taking or planning to take any prohibited medications (see Section 6.8)."}
• {"criterion_text":"- 12. Received another investigational agent, other than C5is ravulizumab or eculizumab, within 30 days or 5 half-lives of the investigational agent prior to Screening, whichever is longer."}
• {"criterion_text":"- 13. Evidence of hepatitis B or hepatitis C infections according to the following criteria: • Testing positive for HBsAg, OR • Testing positive for HBcAb while having a negative HBsAb for hepatitis B. • Testing positive for the HCV antibody for hepatitis C, in exception for participants who have documented successful treatment and a documented sustained virologic response at Screening."}
• {"criterion_text":"- 14. Evidence of HIV infection (positive HIV type 1 or type 2 antibody) at Screening."}
• {"criterion_text":"- 15. Females who are pregnant (positive pregnancy test at Screening or Day 1), nursing, or planning to become pregnant during the study or within 3 days after the last dose of the study intervention. • Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.5."}
• {"criterion_text":"- 2. ANC < 500/μL."}
• {"criterion_text":"- 3. Clinically significant laboratory abnormalities related to liver function, including: • ALT > 2 × ULN or ALT > 3 × ULN for participants with documented liver iron overload defined by serum ferritin values ≥ 500 ng/mL. • Direct bilirubin > 2 × ULN, unless, in the Investigator's opinion, is due to hemolysis or Gilbert’s syndrome based on medical history."}
• {"criterion_text":"- 4. Current evidence of biliary cholestasis."}
• {"criterion_text":"- 5. Known aplastic anemia or other bone marrow failure that requires HSCT or other therapies, including anti-thymocyte globulin and immunosuppressants unless the dosage of immunosuppressant has been stable for at least 12 weeks before Day 1 and is expected to remain stable through Week 12."}
• {"criterion_text":"- 6. History of a major organ transplant (eg, heart, lung, kidney, liver) or HSCT."}
• {"criterion_text":"- 7. Known or suspected complement deficiency."}
• {"criterion_text":"- 8. Active bacterial or viral infection, a body temperature > 38°C on 2 consecutive daily measures, evidence of other infection, or history of any febrile illness within 14 days prior to first study intervention administration."}
• {"criterion_text":"- 9. History or presence of any clinically relevant co-morbidities that makes the participant inappropriate for the study (eg, is likely to result in deterioration of the participant’s condition, affect the participant’s safety during the study, or confound the results of the study)."}

Primary endpoints

• {"endpoint_text":"- Change from Baseline in Hgb at Week 12","definition_or_measurement_approach":"Change from Baseline in hemoglobin (Hgb) measured at Week 12 (as assessed by Hgb change from Baseline at Week 12)."}

Secondary endpoints

• {"endpoint_text":"- •\tPK parameters (Ctrough, Cmax, and accumulation ratio)","definition_or_measurement_approach":"Pharmacokinetic parameters including trough concentration (Ctrough), maximum concentration (Cmax), and accumulation ratio."}
• {"endpoint_text":"- •\tTransfusion avoidance, defined as participants who remain transfusion-free and do not require a transfusion as per protocol-specified guidelines through Weeks 12 and 24","definition_or_measurement_approach":"Transfusion avoidance defined by participants remaining transfusion-free and not requiring transfusion per protocol-specified guidelines through Weeks 12 and 24."}
• {"endpoint_text":"- •\tChange from Baseline in absolute reticulocyte count at Weeks 12 and 24","definition_or_measurement_approach":"Change from baseline in absolute reticulocyte count measured at Weeks 12 and 24."}
• {"endpoint_text":"- •\tChange from Baseline in PedsQL Generic Core Scales score at Weeks 12 and 24","definition_or_measurement_approach":"Change from baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales score at Weeks 12 and 24."}
• {"endpoint_text":"- •\tAcceptability and palatability questionnaire scores","definition_or_measurement_approach":"Scores from acceptability and palatability questionnaires administered to pediatric participants (questionnaire instruments provided as patient-facing documents)."}
• {"endpoint_text":"- •\tChange from Baseline in pediatric FACIT-Fatigue scores at Weeks 12 and 24","definition_or_measurement_approach":"Change from baseline in pediatric FACIT-Fatigue scores measured at Weeks 12 and 24."}
• {"endpoint_text":"- •\tChange from Baseline in Hgb at Week 24","definition_or_measurement_approach":"Change from baseline in hemoglobin (Hgb) measured at Week 24."}
• {"endpoint_text":"- • Change from Baseline in PD parameters (such as AP activity, Bb) during Treatment Period and LTE","definition_or_measurement_approach":"Change from baseline in pharmacodynamic parameters (examples given: AP activity, Bb) during the treatment period and long-term extension (LTE)."}
• {"endpoint_text":"- • Incidence of TEAEs, SAEs, laboratory abnormalities, and events leading to discontinuation","definition_or_measurement_approach":"Safety endpoints including incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), laboratory abnormalities, and events leading to discontinuation."}

France

Earliest CTIS Part Ii Submission Date

27-11-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

427

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Alexion Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD International Holdings LLC

Responsibilities

code:4

Name

Parexel International Corp.

Responsibilities

code:11

Name

Pharmaceutical Product Development LLC

Responsibilities

code:4

Name

Icon Clinical Research Limited

Responsibilities

Hosting of Clinical Site Education ePortal

Name

Syneos Health Inc.

Responsibilities

Investigator payments and vendor oversight

Name

Parexel International Corp.

Responsibilities

code:11

Name

Pharmaceutical Product Development LLC

Responsibilities

code:4

Third parties

• {"country":"United States","full_name":"Pyxant Labs Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Services LLC","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"TMF","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"code:11","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"code:11","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Mapi Research Trust","duties_or_roles":"Assessment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"The Regents Of The University Of Colorado","duties_or_roles":"code:4","organisation_type":"Educational Institution"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Neonstone Limited","duties_or_roles":"Hosting of Clinical Site Education ePortal","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Instem PLC","duties_or_roles":"Document Anonymization","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"code:6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Caerus US 1 Inc.","duties_or_roles":"Clinical Trial Transparency and Disclosure Services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"code:11","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"Assessment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"code:3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Investigator payments and vendor oversight","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Mapi Research Trust","duties_or_roles":"Assessment","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Hosting of Clinical Site Education ePortal","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}