Vedolizumab (Anti-alpha4beta7) in Subjects With HIV Infection Undergoing Analytical Treatment Interruption

• ClinicalTrials.gov Identifier: NCT02788175
• Recruitment Status: Completed
• First Posted: June 2, 2016
• Results First Posted: December 16, 2019
• Last Update Posted: February 24, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV
• Intervention: Biological: Entyvio (Vedolizumab)
• Enrollment: 26

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Vedolizumab in HIV-infected Adults on cART
Arm/Group Description	HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
Period Title: Overall Study
Started [1]	26
Received Study Agent	20
Completed	13
Not Completed	13
Reason Not Completed
Protocol Violation	3
Withdrawal by Subject	4
Ineligible prior to study agent	6
[1] Screened

Baseline Characteristics

Arm/Group Title		Vedolizumab in HIV-infected Adults on cART
Arm/Group Description		HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
Overall Number of Baseline Participants		26
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	26 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Female	4 15.4%
	Male	22 84.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Hispanic or Latino	3 11.5%
	Not Hispanic or Latino	23 88.5%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	8 30.8%
	White	15 57.7%
	More than one race	1 3.8%
	Unknown or Not Reported	2 7.7%

Outcome Measures

1. Primary Outcome

Title	Number of Grade 2 or Higher Related Adverse Events
Description	The primary endpoint was the number of grade 2 or higher adverse events, including serious adverse events, that were probably or definitely related to vedolizumab.
Time Frame	From the start of the initial infusion until up to 72 weeks.

Outcome Measure Data

Analysis Population Description

The analyses included all subjects who received at least one infusion of vedolizumab

Arm/Group Title	Vedolizumab in HIV-infected Adults on cART
Arm/Group Description:	HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: Events
	11

2. Secondary Outcome

Title	Number of Subjects Who Met Criteria to Restart Antiretroviral Therapy Before Week 48
Description	The secondary endpoint was defined as number of subjects who experienced plasma viremia following ATI and met criteria to restart cART before week 48 [a confirmed >30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (>40 copies/mL); a sustained (>4weeks) HIV RNA level of > 1000 copies/mL, or any HIV related symptoms or pregnancy.]
Time Frame	From Week 22 until up to 48 weeks.

Outcome Measure Data

Analysis Population Description

The analyses includes all subjects who entered into the analytical treatment interruption at Week 22

Arm/Group Title	Vedolizumab in HIV-infected Adults on cART
Arm/Group Description:	HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
Overall Number of Participants Analyzed	18
Measure Type: Count of Participants; Unit of Measure: Participants
	13 72.2%

Adverse Events

Time Frame	up to 72 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Vedolizumab in HIV-infected Adults on cART
Arm/Group Description	HIV-infected Adults (age 18 - 65) on CART with suppressed viremia
All-Cause Mortality
	Vedolizumab in HIV-infected Adults on cART
	Affected / at Risk (%)
Total	0/20 (0.00%)
Serious Adverse Events
	Vedolizumab in HIV-infected Adults on cART
	Affected / at Risk (%)
Total	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Neck pain †	1/20 (5.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Vedolizumab in HIV-infected Adults on cART
	Affected / at Risk (%)
Total	19/20 (95.00%)
Blood and lymphatic system disorders
Iron deficiency anaemia †	1/20 (5.00%)
Cardiac disorders
Palpitations †	1/20 (5.00%)
Tachycardia †	1/20 (5.00%)
Gastrointestinal disorders
Abdominal pain †	1/20 (5.00%)
Constipation †	1/20 (5.00%)
Diarrhoea †	2/20 (10.00%)
Hiatus hernia †	1/20 (5.00%)
Nausea †	2/20 (10.00%)
General disorders
Fatigue †	4/20 (20.00%)
Influenza like illness †	1/20 (5.00%)
Pain †	1/20 (5.00%)
Pyrexia †	1/20 (5.00%)
Immune system disorders
Hypersensitivity †	1/20 (5.00%)
Infections and infestations
Acute sinusitis †	1/20 (5.00%)
Bronchitis †	3/20 (15.00%)
Campylobacter gastroenteritis †	1/20 (5.00%)
Campylobacter infection †	1/20 (5.00%)
Epididymitis †	1/20 (5.00%)
Furuncle †	1/20 (5.00%)
Gastroenteritis †	3/20 (15.00%)
Giardiasis †	1/20 (5.00%)
Gonorrhoea †	1/20 (5.00%)
Herpes simplex †	1/20 (5.00%)
Influenza †	1/20 (5.00%)
Nasopharyngitis †	8/20 (40.00%)
Otitis media acute †	1/20 (5.00%)
Pharyngitis †	1/20 (5.00%)
Upper respiratory tract infection †	5/20 (25.00%)
Urinary tract infection †	1/20 (5.00%)
Viral infection †	2/20 (10.00%)
Injury, poisoning and procedural complications
Contusion †	1/20 (5.00%)
Ligament sprain †	1/20 (5.00%)
Investigations
Alanine aminotransferase increased †	4/20 (20.00%)
Aspartate aminotransferase increased †	3/20 (15.00%)
Blood bicarbonate decreased †	8/20 (40.00%)
Blood creatine phosphokinase increased †	2/20 (10.00%)
Blood creatinine increased †	5/20 (25.00%)
Blood glucose decreased †	1/20 (5.00%)
Blood glucose increased †	9/20 (45.00%)
Blood magnesium decreased †	1/20 (5.00%)
Blood phosphorus decreased †	7/20 (35.00%)
Blood potassium decreased †	3/20 (15.00%)
Blood sodium decreased †	2/20 (10.00%)
Blood sodium increased †	2/20 (10.00%)
Eosinophil count increased †	1/20 (5.00%)
Neutrophil count decreased †	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Back pain †	1/20 (5.00%)
Costochondritis †	1/20 (5.00%)
Musculoskeletal pain †	2/20 (10.00%)
Myalgia †	1/20 (5.00%)
Nervous system disorders
Headache †	3/20 (15.00%)
Renal and urinary disorders
Dysuria †	2/20 (10.00%)
Nephrolithiasis †	1/20 (5.00%)
Respiratory, thoracic and mediastinal disorders
Cough †	1/20 (5.00%)
Oropharyngeal pain †	1/20 (5.00%)
Pleurisy †	1/20 (5.00%)
Rhinorrhoea †	1/20 (5.00%)
Skin and subcutaneous tissue disorders
Papule †	1/20 (5.00%)
Pruritus †	1/20 (5.00%)
Rash †	1/20 (5.00%)
Urticaria †	1/20 (5.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Michael C. Sneller
• Organization: NIAID
• Phone: 301-496-0491
• EMail: MSNELLER@niaid.nih.gov

Publications:

Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008 Mar;9(3):301-9. doi: 10.1038/ni1566. Epub 2008 Feb 10.

Cicala C, Martinelli E, McNally JP, Goode DJ, Gopaul R, Hiatt J, Jelicic K, Kottilil S, Macleod K, O'Shea A, Patel N, Van Ryk D, Wei D, Pascuccio M, Yi L, McKinnon L, Izulla P, Kimani J, Kaul R, Fauci AS, Arthos J. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20877-82. doi: 10.1073/pnas.0911796106. Epub 2009 Nov 20.

Byrareddy SN, Kallam B, Arthos J, Cicala C, Nawaz F, Hiatt J, Kersh EN, McNicholl JM, Hanson D, Reimann KA, Brameier M, Walter L, Rogers K, Mayne AE, Dunbar P, Villinger T, Little D, Parslow TG, Santangelo PJ, Villinger F, Fauci AS, Ansari AA. Targeting alpha4beta7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection. Nat Med. 2014 Dec;20(12):1397-400. doi: 10.1038/nm.3715. Epub 2014 Nov 24.

• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
• ClinicalTrials.gov Identifier: NCT02788175
• Other Study ID Numbers: 160118; 16-I-0118
• First Submitted: May 28, 2016
• First Posted: June 2, 2016
• Results First Submitted: November 25, 2019
• Results First Posted: December 16, 2019
• Last Update Posted: February 24, 2020