Trial Outcomes & Findings for A Study of a Single Dose of Inclacumab to Reduce Re-admission in Participants With Sickle Cell Disease and Recurrent Vaso-occlusive Crises (NCT NCT04927247)

Last Updated: 2024-12-11

Results Overview

A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. An admission for a VOC 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. An acute episode of pain with no other cause other than a vaso-occlusive event included: uncomplicated VOC, acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

72 participants

Primary outcome timeframe

Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])

Results posted on

2024-12-11

Participant Flow

In this study, participants with sickle cell disease (SCD), aged greater than or equal to (\>=) 12 years were randomized to receive either inclacumab or placebo for reducing the frequency of re-admissions due to vaso-occlusive crisis (VOC) after an index VOC.

A total of 72 participants were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Inclacumab 30 mg/kg Participants were administered with inclacumab 30 milligram per kilogram (mg/kg) intravenous (IV) infusion on Day 1 as a single dose.	Placebo Participants were administered with placebo IV infusion on Day 1 as a single dose.
Overall Study STARTED	37	35
Overall Study COMPLETED	34	33
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Inclacumab 30 mg/kg Participants were administered with inclacumab 30 milligram per kilogram (mg/kg) intravenous (IV) infusion on Day 1 as a single dose.	Placebo Participants were administered with placebo IV infusion on Day 1 as a single dose.
Overall Study Other	2	1
Overall Study Physician Decision	0	1
Overall Study Adverse Event	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inclacumab 30 mg/kg n=37 Participants Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=35 Participants Participants were administered with placebo IV infusion on Day 1 as a single dose.	Total n=72 Participants Total of all reporting groups
Age, Continuous	23.5 Years STANDARD_DEVIATION 6.95 • n=5 Participants	24.9 Years STANDARD_DEVIATION 8.34 • n=7 Participants	24.2 Years STANDARD_DEVIATION 7.64 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	17 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	33 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])

Population: The intent-to-treat (ITT) population included all randomized participants. Participants without an observed VOC who discontinued the study prior to Day 91 were assumed to have experienced at least one VOC.

Outcome measures

Outcome measures
Measure	Inclacumab 30 mg/kg n=37 Participants Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=35 Participants Participants were administered with placebo IV infusion on Day 1 as a single dose.
Percentage of Participants With at Least 1 VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	45.4 Percentage of participants 95% Confidence Interval 28.7 • Interval 28.7 to 62.2	37.5 Percentage of participants 95% Confidence Interval 20.7 • Interval 20.7 to 54.3

SECONDARY outcome

Timeframe: Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91]) or censored day, whichever occurred earlier

Population: The ITT population included all randomized participants.

A VOC was a complication of SCD characterized by vaso-occlusion presenting as recurrent pain episodes. Time to first VOC that required admission to a healthcare facility and treatment with parenteral pain medication within 90 days was defined as the time between randomization date and onset date of first VOC event. For participants who did not experience a protocol-defined VOC within 90 days of randomization, time to first VOC was censored at the end of their time at risk (participant's end of study date or Study Day 91, whichever was earlier). An admission for a VOC 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. All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD. Kaplan-Meier method used for analysis.

Outcome measures

Outcome measures
Measure	Inclacumab 30 mg/kg n=37 Participants Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=35 Participants Participants were administered with placebo IV infusion on Day 1 as a single dose.
Time to First VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 90 Days of Randomization	NA Days Here "NA" indicates that data could not be estimated as the number of participants with events available was not sufficient for the calculation of median and 95% CI using Kaplan-Meier method.	NA Days Here "NA" indicates that data could not be estimated as the number of participants with events available was not sufficient for the calculation of median and 95% CI using Kaplan-Meier method.

SECONDARY outcome

Timeframe: Within 30 days of randomization (randomization happened on Day 1 [Day 1 to Day 31])

Population: The ITT population included all randomized participants. Participants without an observed VOC who discontinued the study prior to Day 31 were assumed to have experienced at least one VOC.

Outcome measures

Outcome measures
Measure	Inclacumab 30 mg/kg n=37 Participants Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=35 Participants Participants were administered with placebo IV infusion on Day 1 as a single dose.
Percentage of Participants With at Least 1 VOC That Required Admission to a Healthcare Facility and Treatment With Parenteral Pain Medication Within 30 Days of Randomization	8.2 Percentage of participants 95% Confidence Interval 0.0 • Interval 0.0 to 17.3	25.0 Percentage of participants 95% Confidence Interval 9.6 • Interval 9.6 to 40.4

SECONDARY outcome

Timeframe: Within 90 days of randomization (randomization happened on Day 1 [Day 1 to Day 91])

Population: The ITT population included all randomized participants.

VOC leading to a healthcare visit was defined as VOC at (hospital, emergency room, clinic visit, or remote contact with a healthcare provider) that required parenteral pain medication (e.g., parenteral narcotic agents or parenteral nonsteroidal anti-inflammatory drugs \[NSAIDs\]), or an increased treatment with oral narcotics. Complicated VOCs included acute chest syndrome (ACS),hepatic sequestration, splenic sequestration, and priapism. For each participant, the time period at risk for evaluation of VOCs was from date of randomization to the participant's end of study date or study Day 91, whichever was earlier. In this outcome measure adjusted rates of VOCs (percentages) reported were based on estimate from a negative binomial model with the independent variable of treatment group (inclacumab, placebo) and adjusted for baseline hydroxyurea use (yes, no). All on-study VOCs were adjudicated by an independent, blinded VOC Adjudication Committee comprised of experts in SCD.

Outcome measures

Outcome measures
Measure	Inclacumab 30 mg/kg n=37 Participants Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=35 Participants Participants were administered with placebo IV infusion on Day 1 as a single dose.
Rate of VOCs Leading to a Healthcare Visit That Requires Parenteral Pain Medication or an Increase in Treatment With Oral Narcotics Within 90 Days Following Randomization	0.83 Percentage of VOCs 95% Confidence Interval 0.57 • Interval 0.57 to 1.21	0.76 Percentage of VOCs 95% Confidence Interval 0.51 • Interval 0.51 to 1.14

Adverse Events

Inclacumab 30 mg/kg

Serious events: 4 serious events

Other events: 20 other events

Deaths: 1 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Inclacumab 30 mg/kg n=36 participants at risk Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=33 participants at risk Participants were administered with placebo IV infusion on Day 1 as a single dose.
Cardiac disorders Bradycardia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Malaria	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Pneumonia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Sepsis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Renal and urinary disorders Acute kidney injury	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Respiratory, thoracic and mediastinal disorders Haemothorax	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Inclacumab 30 mg/kg n=36 participants at risk Participants were administered with inclacumab 30 mg/kg IV infusion on Day 1 as a single dose.	Placebo n=33 participants at risk Participants were administered with placebo IV infusion on Day 1 as a single dose.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	5.6% 2/36 • Number of events 3 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Blood and lymphatic system disorders Leukocytosis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Blood and lymphatic system disorders Splenomegaly	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Cardiac disorders Palpitations	2.8% 1/36 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Ear and labyrinth disorders Ear pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Eye disorders Conjunctivitis allergic	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Eye disorders Vision blurred	0.00% 0/36 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Gastrointestinal disorders Dyspepsia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Gastrointestinal disorders Gastritis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Gastrointestinal disorders Odynophagia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/36 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Chest pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Fatigue	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Hypothermia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Malaise	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Non-cardiac chest pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Peripheral swelling	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
General disorders Pyrexia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Hepatobiliary disorders Hypertransaminasaemia	5.6% 2/36 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Hepatobiliary disorders Hyperbilirubinaemia	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Malaria	13.9% 5/36 • Number of events 6 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	9.1% 3/33 • Number of events 3 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Upper respiratory tract infection	5.6% 2/36 • Number of events 3 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	6.1% 2/33 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Urinary tract infection	5.6% 2/36 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Cellulitis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Conjunctivitis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Gastroenteritis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Nasopharyngitis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Oral candidiasis	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Respiratory tract infection	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Rhinovirus infection	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Sexually transmitted disease	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Acarodermatitis	0.00% 0/36 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Infections and infestations Gastroenteritis viral	0.00% 0/36 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Injury, poisoning and procedural complications Limb injury	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 2/36 • Number of events 3 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	5.6% 2/36 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Back pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Bone pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	6.1% 2/33 • Number of events 3 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Musculoskeletal and connective tissue disorders Spinal pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Nervous system disorders Headache	11.1% 4/36 • Number of events 5 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Nervous system disorders Dizziness	5.6% 2/36 • Number of events 2 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	3.0% 1/33 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Nervous system disorders Presyncope	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Psychiatric disorders Depression	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Reproductive system and breast disorders Menstruation irregular	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.8% 1/36 • Number of events 1 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.	0.00% 0/33 • Day 1 through Day 161 Safety population included randomized participants who received treatment with study drug.