A Study Evaluating the Presence and Concentration of BRIUMVI™ (Ublituximab) in Breast Milk (PROVIDE)

A Post-marketing Study Evaluating the Presence and Concentration of BRIUMVI™ in Breast Milk (PROVIDE)

The primary objective of the lactation study is to characterize the presence and concentration of BRIUMVI™ in breast milk among breastfeeding participants who receive BRIUMVI™ therapeutically for the treatment of relapsing forms of multiple sclerosis (RMS).

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: TG Therapeutics Clinical Support Team; Phone Number: 1-877-555-8489; Email: clinicalsupport@tgtxinc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population will include breastfeeding individuals with RMS who are exposed to BRIUMVI™.

Description

Inclusion Criteria:

Maternal Criteria:

• Participant has independently decided to be treated with BRIUMVI™ prior to providing consent to participate in the study
• Diagnosis of RMS, to include clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS)
• Willing to breastfeed or pump regularly during the study period to maintain milk supply and exclusively pump breast milk for the 24-hour period of breast milk collection Day 1 post IV dose
• Plans to continue feeding infant breast milk at least throughout the duration of the study and is not weaning

Infant Criteria:

• Gestational age at delivery ≥35 weeks
• Birthweight > 10th percentile
• Weight > 10th percentile as reported by the mother at the time of enrollment

Exclusion Criteria:

Maternal Criteria:

• Any active infection or other condition that would prevent the individual from breastfeeding
• History of breast implants, breast augmentation, or breast reduction surgery that significantly impacts breastfeeding or collection of milk from 1 or both breasts
• History of mastectomy
• Evidence of mastitis or any other significant active infection at Day 1 (pre-dose) that would prevent collection of milk from one or both breasts
• Current use of drugs known to transfer to the breast milk and with established or potential deleterious effects for the infant, including but not limited to aspirin (risk of Reye's syndrome), tetracyclines or fluoroquinolones

Infant Criteria:

- Any abnormality noted or clinically significant medical condition, including cardiac, pulmonary, and liver disease, glucose instability, or active infection at the time of screening that, in the opinion of the investigator, may make implementation of the protocol or interpretation of the trial difficult or would put the infant at risk by participating in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast Milk Collection; Breast milk will be collected of participants with relapsing forms of multiple sclerosis (RMS) who are receiving BRIUMVI™ therapeutically for up to 24 hours to determine concentration of BRIUMVI™ in milk samples.	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Milk Concentration-time Curve from Time 0 to Infinity (AUC0-inf) of BRIUMVI™	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Area Under the Milk Concentration-time Curve from Time 0 to the Last Measurable Observed Concentration (AUC0-last) of BRIUMVI™	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Area Under the Milk Concentration-Time Curve from Time 0 to 24 Hours Post-Dose (AUC0-24) of BRIUMVI™	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Maximum Observed Milk Concentration of BRIUMVI™ (Cmax)	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Observed Milk Concentration of BRIUMVI™ at End of Dosing Interval (Ctrough) of BRIUMVI™	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and at exit Day 90
Time of Cmax (Tmax) of BRIUMVI™ in Milk	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount Excreted (Ae) of BRIUMVI™ in Milk	Total amount of drug excreted in milk (mg) as: Σ(total drug concentration in each milk collection x milk volume in each milk collection)	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Fraction of Dose Excreted (Fe) in Milk of BRIUMVI™	Fraction of dose excreted in milk calculated as Ae/Administered dose	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Infant Dose (ID) of BRIUMVI™	Infant dose = Ʃ drug concentration in each milk collection multiplied by the expressed milk volume in each milk collection.	Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and at exit Day 90
Relative Infant Dose (RID) of BRIUMVI™	Relative infant dose = infant dose milligrams/kilograms (mg/kg)/ [Maternal Dose (mg)/Maternal Bodyweight (kg)] multiplied by 100	Predose Day 1 and at multiple timepoints Post-dose Day 1, Day 2, Day 3, Day 7, Day 10, Day 14, Day 28, Day 60 and Day 90
Number of Infants with Adverse Events		From the signing the inform consent form up to approximately 3 months after the index infusion

Collaborators and Investigators

• Sponsor: TG Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2024
• Primary Completion (Estimated): June 28, 2025
• Study Completion (Estimated): June 28, 2025

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: TG1101-RMS405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No