A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-occlusive Crises

Eligible participants will be administered inclacumab or placebo intravenous (IV) every 12 weeks.

The total duration of treatment for each participant will be 48 weeks.

Participants that complete the study through Week 48 will be provided the opportunity to enroll in an open-label extension (OLE) study.

• Inclacumab (Drug): 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.
• Placebo (Drug): 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

Primary outcomes

• Rate of Vaso-occlusive Crises (VOCs) [Adjudicated] Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. The rate of VOC was defined as number of VOC events per 48 weeks and presented in this outcome measure.

Secondary outcomes

• Time to First VOC Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Time to first VOC was the time between randomization date and onset date of first VOC event during 48 weeks. Kaplan-Meier method was used for estimation.
• Time to Second VOC Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Time to second VOC was the time between randomization date and onset date of second VOC event during 48 weeks. Kaplan-Meier method was used for estimation.
• Percentage of Participants With no VOCs Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), or resulted in a remote contact with a healthcare provider and required parenteral narcotic agents, parenteral NSAIDs, or an increase in treatment with oral narcotics. Participants without an observed VOC who discontinued the study prior to the end of the 48-week treatment period were assumed to had experienced at least one VOC.
• Rate of VOCs Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication [Adjudicated] Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC that required admission to a healthcare facility and treatment with parenteral pain medication where admission included: a hospital admission or an admission to an emergency room, observation unit, or infusion center for >= 12 hours, or 2 visits to an emergency room, observation unit, or infusion center over a 72-hour period. The rate of VOC was defined as number of VOC events per 48 weeks; rate of VOCs which required admission to a healthcare facility and treatment with parenteral pain medication is presented in this outcome measure.
• Rate of Inpatient Hospitalization Days for a VOC Through Week 48 [Randomization (Day 1) up to Week 48]: A VOC was defined as an acute episode of pain that: had no medically determined cause other than a vaso-occlusive event; resulted in a visit to a medical facility hospitalization. For each VOC event requiring inpatient hospitalization (regardless of treatment received) during the 48-week, the number of days hospitalized were determined based on the hospital admission and discharge dates. The rate of inpatient hospitalization days was defined as number of inpatient hospitalization days for a VOC per 48 weeks and presented in this outcome measure.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Day 1 up to Week 60 (12 week of follow-up post Week 48)]: An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. A TEAE was defined as an AE with an onset after the initiation of dosing for the first dose of study drug. A serious adverse events (SAE) or serious suspected adverse reaction is an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, results in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization and congenital anomaly/birth defect. AEs included both serious and all non-SAEs.

Sex: All, ages: 12 Years to any

Inclusion Criteria:

1. Participant has a confirmed diagnosis of SCD (HbSS, HbSC, HbSB0 thalassemia, or HbSB+ thalassemia genotype).

   Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.
2. Participant is male or female, ≥ 12 years of age at the time of informed consent.
3. Participant has experienced between 2 and 10 VOCs within the 12 months prior to the Screening Visit as determined by documented medical history. A prior VOC is defined as an acute episode of pain which:

   * Has no medically determined cause other than a vaso-occlusive event, and
   * Results in a visit to a medical facility (hospital, emergency department, urgent care center, outpatient clinic, or infusion center) or results in a remote contact with a healthcare provider; and
   * Requires parenteral narcotic agents, parenteral nonsteroidal anti- inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics.
4. Participants receiving erythropoiesis-stimulating agents (ESA, e.g., erythropoietin \[EPO\]) must be on a stable dose for at least 90 days prior to the Screening Visit and expected to continue with the stabilized regimen throughout the course of the study.
5. Participants receiving hydroxyurea (HU), L-glutamine, or voxelotor (Oxbryta®) must be on a stable dose for at least 30 days prior to the Screening Visit 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 the Screening Visit
3. Participant weighs > 133 kg (292 lbs.).

Other protocol-defined Inclusion/Exclusion may apply.

Participant flow

Outcome results

• Rate of Vaso-occlusive Crises (VOCs) [Adjudicated] Through Week 48 (Primary), Number, Events per 48 weeks: Inclacumab 1.49 (1.22 to 1.83); Placebo 1.58 (1.30 to 1.93) (p 0.6967)
• Time to First VOC Through Week 48 (Secondary), Median, Weeks: Inclacumab 28.7 (15.7 to 43.1); Placebo 21.6 (17.3 to 28.7) (p 0.4298)
• Time to Second VOC Through Week 48 (Secondary), Median, Weeks: Inclacumab NA (NA to NA); Placebo NA (NA to NA)
• Percentage of Participants With no VOCs Through Week 48 (Secondary), Number, Percentage of participants: Inclacumab 36.0 (27.1 to 45.0); Placebo 25.7 (17.7 to 33.7) (p 0.0912)
• Rate of VOCs Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication [Adjudicated] Through Week 48 (Secondary), Number, Events per 48 weeks: Inclacumab 0.85 (0.65 to 1.10); Placebo 0.83 (0.64 to 1.08) (p 0.9246)
• Rate of Inpatient Hospitalization Days for a VOC Through Week 48 (Secondary), Number, Hospitalization days per 48 weeks: Inclacumab 4.96 (3.05 to 8.07); Placebo 5.37 (3.34 to 8.62) (p =0.8263)
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Secondary), Count of participants, Participants: Inclacumab 87 (3.05 to 8.07); Placebo 97 (3.34 to 8.62)

Adverse events

Time frame: Day 1 up to Week 60 (12 week of follow-up post Week 48)

Serious adverse events by term

Other adverse events by term

171 more terms not shown.

• Study Protocol (PDF, 2023-07-14)
• Statistical Analysis Plan (PDF, 2025-06-06)

• Pfizer CT.gov Call Center, Study director, Pfizer