Clinical trial NCT04654468: A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition
Official title: A Phase III, Multicenter, Single Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-12-04
Enrollment: 51
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will enrol participants aged 12 years or older with a body weight \>= 40 kilograms (kg) diagnosed with PNH who have not been previously treated with complement inhibitor therapy. Approximately 50 participants will be treated with Crovalimab for at least 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Body weight \>= 40 kg at screening.
* Willingness and ability to comply with all study visits and procedures.
* Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
* LDH Levels \>= 2x the ULN at screening.
* Participants who have at least four transfusions during 12 months prior to screening (documented in the medical record).
* Presence of one or more of the following PNH-related signs or symptoms within 3 months of screening.
* Vaccination against Neisseria meningitidis serotypes A, C, W, and Y \< 3 years prior to initiation of study treatment (Day 1)
* Vaccination against Haemophilius influenzae type B and Streptococcus pneumonia according to national vaccination recommendations.
* For participants receiving other therapies (e.g., immunosuppressants, corticosteroids): stable dose for \>= 28 days prior to screening and up to the first drug administration.
* Adequate hepatic and renal function.
* Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 46 weeks (approximately 10.5 months) after the final dose of crovalimab.
* Platelet count \>=30,000 cubic millimeter (mm\^3) at screening
* ANC \> 500/μl at screening

Exclusion Criteria:

* Current or previous treatment with a complement inhibitor.
* History of allogeneic bone marrow transplantation.
* History of Neisseria meningitidis infection within 6 months prior to screening and up to first drug administration.
* Known or suspected immune or hereditary complement deficiency.
* Known HIV infection with CD4 count \< 200 cells per microlitre (cells/µl) within 24 weeks prior to screening.
* Infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 28 days prior to screening and up to the first drug administration, or oral antibiotics within 14 days prior to screening and up to the first drug administration.
* Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration.
* Presence of fever (\>= 38˚C) within 7 days before the first drug administration.
* Splenectomy \< 6 months before screening.
* History of malignancy within 5 years prior to screening and up to the first drug administration.
* Pregnant or intending to become pregnant during the study or within 46 weeks (10.5 months) after the final dose of study treatment.
* Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever is greater.

Primary outcomes:
measure: Mean Percentage of Participants With Hemolysis Control
timeFrame: From Week 5 up to Week 25
measure: Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening
timeFrame: 24 Weeks Prior to Screening, Baseline to Week 25
Secondary outcomes:
measure: Percentage of Participants With Breakthrough Hemolysis (BTH)
timeFrame: Baseline, Week 25
measure: Percentage of Participants With Stabilized Hemoglobin
timeFrame: Baseline, Week 25
measure: Change From Baseline in Fatigue in Adults Aged >=18 Years
timeFrame: Baseline, Week 2, Week 5, Week 9, Week 17, Week 25
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to 7 years
measure: Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, and Infections (Including Meningococcal Meningitis)
timeFrame: Up to 7 years
measure: Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
timeFrame: Up to 7 years
measure: Trough Serum Concentration of Crovalimab Over Time
timeFrame: Up to 7 years
measure: Serum Concentrations of Crovalimab
timeFrame: Up to 7 years
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Crovalimab
timeFrame: Up to 7 years
measure: Terminal Complement Activity as Measured by Liposome Immunoassay (LIA)
timeFrame: Up to 7 years
measure: Change Over Time in Total and Free C5 Concentration
timeFrame: Up to 7 years
measure: Observed Value in Absolute Reticulocyte Count
timeFrame: Up to 7 years
measure: Observed Value in Free Hemoglobin
timeFrame: Up to 7 years
measure: Observed Value in Haptoglobin
timeFrame: Up to 7 years
measure: Percent Change From Baseline in Absolute Reticulocyte Count
timeFrame: Baseline, Week 25
measure: Percent Change From Baseline in Free Hemoglobin
timeFrame: Baseline, Week 25
measure: Percent Change From Baseline in Haptoglobin
timeFrame: Baseline, Week 25
Other outcomes:
Locations:
city: Chengdu City
country: China
facility: West China Hospital, Sichuan University
city: Tianjin City
country: China
facility: Institute of Hematology and Hospital of Blood Disease
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: