Clinical trial NCT04912869: A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD).
Official title: A Phase IB Randomized, Placebo-Controlled Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Patients With Sickle Cell Disease (SCD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: Vaso-occlusive episodes
Pain crisis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-06-03
Enrollment: 30
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: The purpose of this study is to evaluate crovalimab for the treatment of a sickle cell pain crisis (also known as a VOE) that requires hospitalisation in adult and adolescent participants with SCD. The primary objective of this study is safety and will additionally evaluate pharmacokinetics (how crovalimab is processed by your body), pharmacodynamics (how your body reacts to crovalimab) and the preliminary efficacy of crovalimab compared with placebo.


Eligibility criteria: Inclusion Criteria:

* Body weight \>=40 kg.
* Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia).
* Vaccination against Neisseria Meningitidis serotypes A, C, W, and Y.
* Vaccinations against H. influenzae type B and S. pneumoniae.
* Participants vaccinated against SARS-CoV-2 are eligible, as long as it has been 3 days or more after inoculation with the vaccine.
* Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics.
* Adequate hepatic and renal function.
* Hemoglobin \>=5 grams/deciliter (g/dL)
* Platelet count \>=100,000/microliter (µL)
* Participants receiving SCD-directed therapies must be on a stable dose for \>=28 days.
* For female participants of childbearing potential, an agreement to remain abstinent or use contraception for 322 days (approximately 10.5 months) after the dose of study treatment.

Exclusion Criteria:

* More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit.
* Pain related to the current VOE ongoing for \>36 hours.
* Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism.
* Pain atypical of an acute uncomplicated VOE.
* Evidence of or suspicion of ACS.
* Evidence or high suspicion of a severe systemic infection.
* Major surgery and/or hospitalization for any reason within 30 days.
* History of Neisseria meningitidis infection within 6 months prior.
* Known HIV infection with a documented CD4 count \<200 cells/µL.
* Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol.
* Immunized with a live attenuated vaccine within 30 days.
* History of hematopoietic stem cell transplant.
* Known or suspected hereditary complement deficiency.
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration.
* Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Day 84
measure: Percentage of Participants with Infusion-Related Reactions and Hypersensitivity
timeFrame: Baseline up to Day 84
Secondary outcomes:
measure: Time to Improvement of the Primary Acute Uncomplicated VOE From Baseline
timeFrame: Baseline up to Day 84
measure: Total Cumulative Opioid Dose From Baseline
timeFrame: Baseline up to Day 84
measure: Time to Discontinuation of all Parenteral Opioids From Baseline
timeFrame: Baseline up to Day 84
measure: Time to Readiness For Hospital Discharge From Baseline
timeFrame: Baseline up to Day 84
measure: Time to Hospital Discharge From Baseline
timeFrame: Baseline up to Day 84
measure: Time to a Confirmed Decrease in Pain Score of at Least 2 Points From the Maximal Pre-dose Pain Score
timeFrame: Baseline up to Day 84
measure: Change in Pain Score From the Maximal Pre-dose Pain Score to the Score at Hospital Discharge
timeFrame: Baseline up to Day 84
measure: Percentage of Participants who Develop Acute Chest Syndrome (ACS)
timeFrame: Baseline up to Day 28
measure: Percentage of Participants Requiring Intensive Care Unit (ICU)/Critical Care Admission for SCD-related Complications
timeFrame: Baseline up to Day 84
measure: Percentage of Participants Requiring Blood Transfusion for SCD-related Complications
timeFrame: Baseline up to Day 84
measure: Readmission Rate for a VOE or VOE-related Event Within 28 days of Discharge of the Primary Acute Uncomplicated VOE
timeFrame: Baseline up to Day 84
measure: Serum Concentrations of Crovalimab Over Time
timeFrame: Baseline up to Day 84
measure: Change in PD Biomarkers Including Complement Activity (CH50) Over Time
timeFrame: Baseline up to Day 84
measure: Change Over Time in Free C5 Concentration
timeFrame: Baseline up to Day 84
measure: Change Over Time in Soluble Complement 5b 9 (sC5b-9) Concentration
timeFrame: Baseline up to Day 84
measure: Percentage of Participants with Anti-Drug Antibodies to Crovalimab
timeFrame: Baseline up to Day 84
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children'S Healthcare of Atlanta
state: Georgia
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
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: Créteil
country: France
facility: CHU Henri Mondor
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: Beirut
country: Lebanon
facility: American University of Beirut - Medical Center
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: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: