A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises

• ClinicalTrials.gov Identifier: NCT04927247
• Recruitment Status: Terminated
• First Posted: June 15, 2021
• Last Update Posted: March 25, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 26, 2021
• First Posted Date: June 15, 2021
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: December 13, 2021
• Actual Primary Completion Date: November 24, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2021)

Re-admission for a VOC within 90 days of randomization [ Time Frame: Within 90 days of randomization ]

Following an index VOC, the proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 10, 2021)

• Time to first re-admission for a VOC [ Time Frame: Within 90 days of randomization ]
  Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication
• Readmission for a VOC within 30 days [ Time Frame: Within 30 days of randomization ]
  Proportion of participants with at least 1 VOC that required admission to a healthcare facility and treatment with parenteral pain medication
• Rate of VOCs leading to healthcare visits [ Time Frame: Within 90 days following randomization ]
  Rate of VOCs leading to a healthcare visit that requires parenteral pain medication or an increase in treatment with oral narcotics
• Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through Day 91 ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 10, 2021)

• PD parameter (P-selectin inhibition) [ Time Frame: Through Day 91 ]
  To characterize the pharmacodynamics (PD) (P-selectin inhibition) of inclacumab at 30 mg/kg
• PD parameter (Platelet Leukocyte Aggregation) [ Time Frame: Through Day 91 ]
  To characterize the pharmacodynamics (PD) (PLA) of inclacumab at 30 mg/kg

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises
• Brief Summary: This Phase 3 study will assess the safety and efficacy of a single dose of inclacumab, a P-selectin inhibitor, for a vaso-occlusive crisis (VOC) after an index VOC in participants with sickle cell disease (SCD). Participants will be randomized to receive either inclacumab or placebo.

Detailed Description

The study will include approximately 280 adult and adolescent participants (≥ 12 years of age) with SCD.

Eligible participants will be administered inclacumab or placebo intravenous (IV) as a single dose.

Participants that complete the study through Day 90 will be provided the opportunity to enroll in an open-label extension (OLE) study.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double blind study

Primary Purpose: Treatment

Condition

• Sickle Cell Disease
• Vaso-occlusive Crisis
• Vaso-occlusive Pain Episode in Sickle Cell Disease

Intervention

• Drug: Inclacumab
  Inclacumab will be supplied in single use 10 mL vials at a concentration of 50 mg/mL. One vial contains 500 mg of inclacumab. This is a liquid concentrate for IV infusion.
• Drug: Placebo
  Placebo will be supplied in single use 10 mL vials containing the same ingredients without the active drug. Placebo will be prepared as a liquid concentrate for IV infusion and administered in the same manner as active study drug.

Study Arms

• Experimental: inclacumab 30 mg/kg
  Inclacumab 30 mg/kg administered intravenously (IV)
  Intervention: Drug: Inclacumab
• Placebo Comparator: placebo
  Placebo administered IV
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 12, 2023): 72
• Original Estimated Enrollment (submitted: June 10, 2021): 280
• Actual Study Completion Date: November 24, 2023
• Actual Primary Completion Date: November 24, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participant has an index VOC. The index VOC is any VOC that required admission to a healthcare facility and treatment with parenteral pain medication. An admission for the index VOC includes:

   1. A hospital admission, or
   2. An admission to an emergency room, observation unit, or infusion center for ≥ 12 hours, or
   3. 2 visits to an emergency room, observation unit, or infusion center over a 72-hour period

   for an acute episode of pain with no other cause other than a vaso- occlusive event that includes the following:

   • Uncomplicated VOC,
   • Acute chest syndrome (ACS),
   • Acute hepatic sequestration,
   • Acute splenic sequestration, or
   • Priapism.
2. Participant has a confirmed diagnosis of SCD (any genotype). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing at Baseline.
3. Participant is male or female, ≥ 12 years of age at the time of informed consent.

4. Participant has experienced between 2 and 10 VOCs within the 12 months prior to Screening as determined by documented medical history. The index VOC is not to be considered as one of the 2 to 10 events. A prior VOC is defined as an acute episode of pain that:

   1. Has no medically determined cause other than a vaso-occlusive event, and
   2. Results in a visit to a healthcare facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and
   3. Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics.
5. Participants receiving erythropoiesis-stimulating agents (ESA, e.g., erythropoietin [EPO]) must be on a stable dose for at least 90 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study.
6. Participants receiving hydroxyurea (HU), L-glutamine, or voxelotor (Oxbryta®) must be on a stable dose for at least 30 days prior to Screening and expected to continue with the stabilized regimen throughout the course of the study.

Exclusion Criteria:

1. Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion).
2. Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days prior to Screening.
3. Participant weighs > 133 kg (292 lbs.).

Other protocol-defined Inclusion/Exclusion may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Colombia, France, Germany, Italy, Kenya, Lebanon, Nigeria, Oman, Saudi Arabia, Turkey, United Kingdom, United States, Zambia

Administrative Information

• NCT Number: NCT04927247
• Other Study ID Numbers: GBT2104-132; C5361002 ( Other Identifier: Alias Study Number ); 2020-005287-60 ( EudraCT Number: CTIS (EU) ); 2020-005287-60 ( Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Global Blood Therapeutics
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Global Blood Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2024