CROSSWALK-c: 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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05075824

Collaborator

(none)

Enrollment

Locations

Arms

34.1

Anticipated Duration (Months)

12.9

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Crovalimab Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Mar 9, 2022

Anticipated Primary Completion Date :

Jul 26, 2024

Anticipated Study Completion Date :

Jan 10, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crovalimab Participants will receive a loading series of Crovalimab comprised of an intravenous (IV) loading dose on Day 1, followed by weekly Crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 48 weeks of treatment.	Drug: Crovalimab Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 kg and 100 kg) or 1500 mg IV (for participants with body weight >= 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, crovalimab will be administered at a dose of 680 mg SC (for participants with body weight between 40 kg and 100 kg) or 1020 mg SC (for participants with body weight >= 100 kg). Dosing schedule will be as per Arm Description.
Placebo Comparator: Placebo Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment.	Drug: Placebo Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab.

Arm

Intervention/Treatment

Experimental: Crovalimab

Participants will receive a loading series of Crovalimab comprised of an intravenous (IV) loading dose on Day 1, followed by weekly Crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 48 weeks of treatment.

Drug: Crovalimab

Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 kg and 100 kg) or 1500 mg IV (for participants with body weight >= 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, crovalimab will be administered at a dose of 680 mg SC (for participants with body weight between 40 kg and 100 kg) or 1020 mg SC (for participants with body weight >= 100 kg). Dosing schedule will be as per Arm Description.

Placebo Comparator: Placebo

Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment.

Drug: Placebo

Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab.

Outcome Measures

Primary Outcome Measures

Annualized rate of medical facility VOEs (AVR) [Up to 48 weeks]

Secondary Outcome Measures

Annualized rate of home VOE [Up to 48 weeks]
Annualized rate of uncomplicated medical facility VOE [Up to 48 weeks]
Annualized rate of Acute Chest Syndrome (ACS) [Up to 48 weeks]
Annualized rate of days hospitalized for medical facility VOE [Up to 48 weeks]
Annualized rate of days hospitalized for treatment of non-VOE complications of SCD [Up to 48 weeks]
Time to first medical facility VOE from randomization [Up to 48 weeks]
Change in urinary albumin-creatinine ratio [Baseline up to Week 49]
Change in Tricuspid Regurgitant Jet Velocity (TRV) [Baseline up to Week 49]
Percentage of Participants with TRV >2.5 m/s [Baseline up to Week 49]
Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in Adults [Baseline up to Week 49]
Percentage of Participants with Adverse Events (AEs) [Up to 72 weeks]
Serum Concentrations of Crovalimab over time [Up to 48 weeks]
Percentage of Participants with Anti-Drug Antibodies to Crovalimab [Up to 48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 and Vaccinations against H. influenza type B and

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 6 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 6 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
2	Università degli Studi della Campania Luigi Vanvitelli; UOC Ematologia ed oncologia pediatrica	Napoli	Campania	Italy	80138
3	Ospedale Galliera; S.S.D. Ematologia	Genova	Liguria	Italy	16128
4	Azienda Ospedaliera di Verona-Policlinico G.B. Rossi; Medicina Interna	Verona	Veneto	Italy	37134
5	Hospital Universitari Vall d'Hebron; Servicio de Hematologia	Barcelona		Spain	08035
6	Hospital General Univ. Gregorio Maranon	Madrid		Spain	28009
7	Hospital Universitario Virgen del Rocio; Servicio de Hematologia	Sevilla		Spain	41013

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT05075824

Other Study ID Numbers:

BO42451
2020-004839-25

First Posted:

Oct 13, 2021

Last Update Posted:

Aug 3, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Hoffmann-La Roche

Vaso-occlusive episodes

Pain crisis

Additional relevant MeSH terms:

Anemia, Sickle Cell

Study Results

No Results Posted as of Aug 3, 2022