Clinical trial NCT05075824: A Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)
Official title: A Randomized Double-Blind Phase IIA Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Keywords: Vaso-occlusive episodes
Pain crisis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-10-13
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the efficacy, safety and pharmacokinetics of crovalimab compared with placebo as adjunct therapy in the prevention of VOEs in participants with SCD.


Eligibility criteria: Inclusion Criteria:

* Body weight \>=40 kg.
* Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia).
* Two or more (\>=2) to \<=10 documented VOEs in the 12 months prior to randomisation.
* If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons.
* If receiving erythropoietin, the participant must have been prescribed this medication for the preceding 3 months and be dose-stabilised for at least 3 months prior to study enrollment.
* Vaccination against N. meningitides serotypes A, C, W, and Y and Vaccinations against H. influenza type B and S. pneumonia.
* Participants who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation.
* Adequate hepatic and renal function.
* For women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of study treatment.

Exclusion Criteria:

* History of hematopoietic stem cell transplant.
* Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study.
* History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment.
* Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial.
* Hemoglobin \<6 g/dL.
* Known or suspected hereditary complement deficiency.
* Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration.
* Presence of fever (\>=38 degrees Celsius) within 7 days before the first drug administration.
* Immunised with a live attenuated vaccine within 1 month before first drug administration.
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the final dose of study treatment.
* Known HIV infection with documented CD4 count \<200 cells/microliter within 24 weeks prior to screening.
* History of N. meningitidis infection within the prior 6 months.

Primary outcomes:
measure: Annualized rate of medical facility VOEs (AVR)
timeFrame: Baseline up to Week 49
Secondary outcomes:
measure: Annualized rate of home VOE
timeFrame: Baseline up to Week 49
measure: Annualized rate of uncomplicated medical facility VOE
timeFrame: Baseline up to Week 49
measure: Annualized rate of Acute Chest Syndrome (ACS)
timeFrame: Baseline to up Week 49
measure: Annualized rate of days hospitalized for medical facility VOE
timeFrame: Baseline up to Week 49
measure: Annualized rate of days hospitalized for treatment of non-VOE complications of SCD
timeFrame: Baseline up to Week 49
measure: Time to first medical facility VOE from randomization
timeFrame: Baseline up to Week 49
measure: Change in urinary albumin-creatinine ratio
timeFrame: Baseline up to Week 49
measure: Change in Tricuspid Regurgitant Jet Velocity (TRV)
timeFrame: Baseline up to Week 49
measure: Percentage of Participants with TRV >2.5 m/s
timeFrame: Week 49
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in Adults
timeFrame: Baseline up to Week 49
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 91 weeks
measure: Serum Concentrations of Crovalimab over time
timeFrame: Baseline up to Week 49
measure: Percentage of Participants with Anti-Drug Antibodies to Crovalimab
timeFrame: Baseline up to Week 49
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: Rio Grande Do Sul
city: Botucatu
country: Brazil
facility: UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clínicas Faculdades Médicas de Ribeirão Preto
state: São Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: HEMORIO
city: São Paulo
country: Brazil
facility: Hospital Samaritano
city: Créteil
country: France
facility: CHU Henri Mondor
city: Napoli
country: Italy
facility: Università degli Studi della Campania Luigi Vanvitelli
state: Campania
city: Verona
country: Italy
facility: Azienda Ospedaliera di Verona-Policlinico G.B. Rossi
state: Veneto
city: Eldoret
country: Kenya
facility: International Cancer Institute (ICI)
city: Nairobi
country: Kenya
facility: Gertrude's Children Hospital
city: Tripoli
country: Lebanon
facility: Hopital Nini
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC Location VUMC
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Hospital
city: Madrid
country: Spain
facility: Hospital General Univ. Gregorio Maranon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Adana
country: Turkey
facility: Adana Acibadem Hospital; Pediatric Hematology
city: Adana
country: Turkey
facility: Cukurova University Medical Faculty Balcali Hospital
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Hastanesi
city: London
country: United Kingdom
facility: Central Middlesex Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: