Colitis, Ulcerative, Crohn's Disease
Conditions
Keywords
Lactation, Lactating Women, Vedolizumab, Colitis Ulcerative, Crohn's Disease, Crohn's
Brief summary
The purpose of this study is to assess the concentration of vedolizumab in breast milk of lactating women with active ulcerative colitis (UC) or Crohn's disease (CD) who are receiving vedolizumab therapeutically.
Detailed description
The drug being tested in this study is called vedolizumab. This post-marketing milk-only lactation study will assess concentrations of vedolizumab in breast milk of lactating women with active UC or CD who are receiving vedolizumab therapeutically. The study will enroll approximately 12 participants. All participants who received an established vedolizumab maintenance regimen or has completed induction therapy for the treatment of active UC or CD. 30-minute IV infusion of 300 mg vedolizumab. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 3 months. Participants will make visits to clinic, study site or HCP office at Screening, Check-in (Day -1). Visits on Days 4, 8, 15, or 29 may be completed at the participant's home setting in the presence of a qualified nurse, or at a clinic, study site or other HCP office. The study exit/follow-up safety assessment will occur on Day 57(±3).
Interventions
DRUGVedolizumab
Vedolizumab IV infusion
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Is capable of understanding and complying with protocol requirements. 2. Signs and dates as written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Is female and at least 18 years of age at the time of informed consent. 4. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent and throughout the duration of the study. 5. Is on established vedolizumab maintenance therapy and received at least 1 dose of 300 mg of vedolizumab IV postpartum or has completed vedolizumab induction therapy (300 mg of vedolizumab IV at Week 0, Week 2, and Week 6), which has been commenced by the participant's treating physician for the treatment of active UC or CD prior to enrolling in this study. 6. Has delivered a single, normal term infant (at least 37 weeks' gestation) that is, a mother-infant pair is required. 7. Is at least 5 weeks postpartum by Day 1. 8. Lactation is well established, and the mother is exclusively breast feeding her infant (or not providing more than 1 supplemental bottle of formula/day) when enrolled in the study. 9. Participant has independently decided to be treated with vedolizumab or to breastfeed prior to providing consent to participate in this study. 10. Plans to continue breastfeeding at least throughout the duration of this study. 11. Agrees to use only the emollient or nipple cream recommended by the investigator for use during the sampling period.
Exclusion criteria
1. Has received any investigational compound or approved biologic or biosimilar agent, except for vedolizumab within 60 days prior to enrollment in the study. 2. Within 30 days prior to enrollment, the participant has received any of the following for the treatment of underlying disease: * Nonbiologic therapies \[example (eg), cyclosporine\], other than those listed in the protocol. * An approved nonbiologic therapy in an investigational protocol. 3. Has received any live vaccinations within 30 days prior to vedolizumab administration. 4. Has clinically significant infection (eg, pneumonia, pyelonephritis) or chronic infection within 30 days prior to enrollment. 5. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 6. Has evidence of unstable or uncontrolled, clinically significant cardiovascular, central nervous system, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic or other medical disorder, including serious allergy, asthma, hypoxemia, hypertension, seizures or allergic skin rash that, in the opinion of the investigator, would confound the study results or compromise participant safety. Additionally, if there is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking vedolizumab, or a similar drug that might interfere with the conduct of the study. 7. Had any surgical procedure requiring general anesthesia within 30 days prior to enrollment or is planning to undergo major surgery during the study period. 8. Has any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and (c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to enrollment. Participants with remote history of malignancy (eg, greater than (\>) 10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to enrollment. 9. Has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease. 10. Has a positive progressive multifocal leukoencephalopathy subjective symptom checklist at screening. 11. Has a current or recent history (within 1 year prior to enrollment) of alcohol dependence or illicit drug use. 12. Has active psychiatric problems that, in the investigator's opinion, may interfere with compliance with the study procedures. 13. Is unable to participate in all the study visits or comply with study procedures. 14. Has history of breast implants, breast augmentation, or breast reduction surgery. 15. Has a prior history of difficulty establishing lactation. 16. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table. 17. Has donated or lost 450 milliliters or more of her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Vedolizumab in Breast Milk at Predose on Day 1 | Day 1 (60 minutes prior to the start of infusion) | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by enzyme-linked immunosorbent assay (ELISA). Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk at 1 Hour After the End of Infusion on Day 1 | Day 1 (approximately 60 minutes after the end of infusion) | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk on Day 4 | Day 4 | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk on Day 8 | Day 8 | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk on Day 15 | Day 15 | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk on Day 29 | Day 29 | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W). |
| Concentration of Vedolizumab in Breast Milk on Day 57 | Day 57 | Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk in participants with analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in the United States from 29 November 2017 to 22 February 2019.
Pre-assignment details
Lactating women with a diagnosis of active ulcerative colitis (UC) or Crohn's disease (CD) being treated with vedolizumab were enrolled to receive a single vedolizumab 300 milligrams (mg) dose intravenous (IV).
Participants by arm
| Arm | Count |
|---|---|
| Vedolizumab 300 mg Vedolizumab 300 mg, IV infusion over 30-minutes, single dose on Day 1. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Pretreatment Event/ Adverse Event | 1 |
Baseline characteristics
| Characteristic | Vedolizumab 300 mg |
|---|---|
| Age, Continuous | 31.8 years STANDARD_DEVIATION 3.71 |
| Alcohol Status Current Drinker | 4 Participants |
| Alcohol Status Ex-drinker | 2 Participants |
| Alcohol Status Has Never Drunk | 5 Participants |
| Body Mass Index (BMI) | 24.78 kg/m^2 STANDARD_DEVIATION 5.534 |
| Breastfed in the Past No | 5 Participants |
| Breastfed in the Past Yes | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fail to Thrive for Previously Breastfed Infants No | 6 Participants |
| Female Reproductive Status Female of Childbearing Potential | 10 Participants |
| Female Reproductive Status Surgically Sterile | 1 Participants |
| Height | 158.9 centimeter (cm) STANDARD_DEVIATION 7.12 |
| Problems with Producing Breast Milk for Previously Breastfed Infants No | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 11 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
| Smoking Status Never Smoked | 11 Participants |
| Weight | 62.72 kilograms (kg) STANDARD_DEVIATION 15.924 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 3 / 11 |
| serious Total, serious adverse events | 1 / 11 |
Outcome results
Primary
Concentration of Vedolizumab in Breast Milk at 1 Hour After the End of Infusion on Day 1
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 1 (approximately 60 minutes after the end of infusion)
Population: PK Set included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration at the given timepoint. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at 1 Hour After the End of Infusion on Day 1 | Q4W | 0.1490 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at 1 Hour After the End of Infusion on Day 1 | Q6W | 0 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at 1 Hour After the End of Infusion on Day 1 | Q8W | 0.03756 ug/mL | Standard Deviation 0.025572 |
Primary
Concentration of Vedolizumab in Breast Milk at Predose on Day 1
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by enzyme-linked immunosorbent assay (ELISA). Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 1 (60 minutes prior to the start of infusion)
Population: Pharmacokinetic Set (PK) included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at Predose on Day 1 | Q4W | 0.1350 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at Predose on Day 1 | Q6W | 0 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk at Predose on Day 1 | Q8W | 0.03161 ug/mL | Standard Deviation 0.024327 |
Primary
Concentration of Vedolizumab in Breast Milk on Day 15
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 15
Population: PK Set included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 15 | Q4W | 0.2280 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 15 | Q6W | 0.1270 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 15 | Q8W | 0.1708 ug/mL | Standard Deviation 0.069017 |
Primary
Concentration of Vedolizumab in Breast Milk on Day 29
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 29
Population: PK Set included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 29 | Q4W | 0.1560 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 29 | Q6W | 0.06860 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 29 | Q8W | 0.1039 ug/mL | Standard Deviation 0.040445 |
Primary
Concentration of Vedolizumab in Breast Milk on Day 4
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 4
Population: PK Set included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration at the given timepoint. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 4 | Q4W | 0.3050 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 4 | Q6W | 0.1650 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 4 | Q8W | 0.2634 ug/mL | Standard Deviation 0.1484 |
Primary
Concentration of Vedolizumab in Breast Milk on Day 57
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk in participants with analysis of vedolizumab concentration from the pooled milk sample was done by ELISA.
Time frame: Day 57
Population: Participants from PK Set, included all participants who were enrolled and received 1 dose of vedolizumab in study and had at least 1 measurable milk concentration, who received vedolizumab Q8W regimen prior to Day 1 with data available for this outcome measure were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 57 | 0.04673 ug/mL | Standard Deviation 0.020966 |
Primary
Concentration of Vedolizumab in Breast Milk on Day 8
Milk from each breast was completely emptied using an electric milk pump at the specified time point for the determination of vedolizumab concentrations in the milk. Analysis of vedolizumab concentration from the pooled milk sample was done by ELISA. Participants unable to return to the clinic could have their milk samples collected at home by a qualified and trained homecare nurse. Participants were categorized as per their past vedolizumab regimens, received prior to Day 1: vedolizumab every 4 weeks (Q4W), vedolizumab every 6 weeks (Q6W), vedolizumab every 8 weeks (Q8W).
Time frame: Day 8
Population: PK Set included all participants who were enrolled and received 1 dose of vedolizumab in the study and had at least 1 measurable milk concentration. Number analyzed is the number of participants who received specific vedolizumab regimen prior to Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 8 | Q4W | 0.3050 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 8 | Q6W | 0.1410 ug/mL | — |
| Vedolizumab 300 mg | Concentration of Vedolizumab in Breast Milk on Day 8 | Q8W | 0.2113 ug/mL | Standard Deviation 0.10299 |