Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection

• ClinicalTrials.gov Identifier: NCT00594880
• Recruitment Status: Completed
• First Posted: January 16, 2008
• Results First Posted: February 10, 2015
• Last Update Posted: February 10, 2015
• Sponsor: The Wistar Institute
• Collaborators: National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID); Hoffmann-La Roche
• Information provided by (Responsible Party): Luis Montaner, The Wistar Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections
• Interventions: Drug: Pegylated Interferon-alpha 2a, 180 mcg/week sc; Drug: Pegylated Interferon-alpha 2a, 90 mcg/week sc
• Enrollment: 23

Participant Flow

Recruitment Details	locations: medical clinics (Hospital of the University of Pennsylvania, Jonathan Lax clinic, Drexel University Hospital) Recruitment period: may 8, 2008 to May 27, 2010
Pre-assignment Details	subjects were randomized to the pegasys dose of 180 or 90 mcg/week four weeks after enrollment (week 0: eligibility determination; week 4: enrollment; week 8: randomization and treatment initiation; week 13: ART interruption; week 25: primary endpoint; week 37: secondary endpoints)

Arm/Group Title	Pegasys 180 mcg/Week	Pegasys 90 mcg/Week
Arm/Group Description	ART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc Pegylated Interferon-alpha 2a, 180 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints	ART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc Pegylated Interferon-alpha 2a, 90 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
Period Title: Overall Study
Started	12	11
Completed	10	10
Not Completed	2	1
Reason Not Completed
Withdrawal by Subject	1	1
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		Pegasys 180 mcg/Week	Pegasys 90 mcg/Week	Total
Arm/Group Description		ART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc Pegylated Interferon-alpha 2a, 180 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints	ART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc Pegylated Interferon-alpha 2a, 90 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints	Total of all reporting groups
Overall Number of Baseline Participants		12	11	23
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	11 participants	23 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	12 100.0%	11 100.0%	23 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
Age	Number Analyzed	12 participants	11 participants	23 participants
		45.5; (42.8 to 48.5)	44; (32 to 49.5)	45; (40.5 to 49.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	12 participants	11 participants	23 participants
	Female	3 25.0%	1 9.1%	4 17.4%
	Male	9 75.0%	10 90.9%	19 82.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	12 participants	11 participants	23 participants
		12	11	23

Outcome Measures

1. Primary Outcome

Title	HIV Viral Load < 400 Copies/ml
Description	% of individuals maintaining viral suppression (VL < 400 copies/ml) as compared to the anticipated rate of viral suppression in individuals interrupting ART without interferon (9%)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

excluded 2 withdrawal of consent and 1 lost to follow-up

Arm/Group Title	Pegasys 180 mcg/Week	Pegasys 90 mcg/Week
Arm/Group Description:	ART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc Pegylated Interferon-alpha 2a, 180 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints	ART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc Pegylated Interferon-alpha 2a, 90 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
Overall Number of Participants Analyzed	10	10
Measure Type: Number; Unit of Measure: percentage of participants
	40	50

2. Secondary Outcome

Title	HIV Viral Load < 48 Copies/ml
Description	% of individuals maintaining VL < 48 copies/ml while on pegylated interferon alpha-2a treatment without ART
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

% of subjects maintaining VL < 48 copies/ml after 12 weeks of treatment

Arm/Group Title	180 mcg/Week	90 mcg/Week
Arm/Group Description:	Patients receiving 180 micrograms/week of pegylated interferon alpha-2a	Patients receiving 90 micrograms/week of pegylated interferon alpha-2a
Overall Number of Participants Analyzed	10	10
Measure Type: Number; Unit of Measure: percentage of participants
	10	30

3. Secondary Outcome

Title	HIV Viral Load < 400 Copies/ml
Description	% of individuals maintaining viral suppression (VL < 400 copies/ml) as compared to the anticipated rate of viral suppression in individuals interrupting ART without interferon (9%)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

percent of consenting eligible participants (n=8) with VL < 400 at week 24 of treatment

Arm/Group Title	180 mcg/Week	90 mcg/Week
Arm/Group Description:	Arm 1 subjects with VL < 400 at week 12 of treatment who elected to continue study treatment for an additional 12 weeks	Arm 2 subjects with VL < 400 at week 12 of treatment who elected to continue study treatment for an additional 12 weeks
Overall Number of Participants Analyzed	3	5
Measure Type: Number; Unit of Measure: percentage of eligible participants
	67	80

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Pegasys 180 mcg/Week		Pegasys 90 mcg/Week
Arm/Group Description	ART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc Pegylated Interferon-alpha 2a, 180 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints		ART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc Pegylated Interferon-alpha 2a, 90 mcg/week sc : Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL < 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
All-Cause Mortality
	Pegasys 180 mcg/Week		Pegasys 90 mcg/Week
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Pegasys 180 mcg/Week		Pegasys 90 mcg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.67%)		3/11 (27.27%)
Blood and lymphatic system disorders
Neutropenia †	1/12 (8.33%)	1	0/11 (0.00%)	0
Hepatobiliary disorders
Liver toxicity † [1]	0/12 (0.00%)	0	1/11 (9.09%)	1
Psychiatric disorders
depression * [2]	1/12 (8.33%)	1	2/11 (18.18%)	2
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; [1] elevated ALT (grade 3 ACTG); [2] based on PHQ2/9 questionnaire self evaluatiuon
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Pegasys 180 mcg/Week		Pegasys 90 mcg/Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0.00%)		0/11 (0.00%)

Limitations and Caveats

The follwing limitations of this study should be noted:

• Small number of participants enrolled
• Lack of a control arm interrupting ART without immunotherapy

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Luis Montaner
• Organization: the Wistar Institute
• Phone: 215 898 3934
• EMail: montaner@mail.wistar.org

Publications of Results:

Azzoni L, Foulkes AS, Papasavvas E, Mexas AM, Lynn KM, Mounzer K, Tebas P, Jacobson JM, Frank I, Busch MP, Deeks SG, Carrington M, O'Doherty U, Kostman J, Montaner LJ. Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. J Infect Dis. 2013 Jan 15;207(2):213-22. doi: 10.1093/infdis/jis663. Epub 2012 Oct 26.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chitre AS, Kattah MG, Rosli YY, Pao M, Deswal M, Deeks SG, Hunt PW, Abdel-Mohsen M, Montaner LJ, Kim CC, Ma A, Somsouk M, McCune JM. A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function. PLoS Pathog. 2018 Mar 5;14(3):e1006806. doi: 10.1371/journal.ppat.1006806. eCollection 2018 Mar.

• Responsible Party: Luis Montaner, The Wistar Institute
• ClinicalTrials.gov Identifier: NCT00594880
• Other Study ID Numbers: DAIDS-ES 10401; U01AI065279 ( U.S. NIH Grant/Contract )
• First Submitted: January 4, 2008
• First Posted: January 16, 2008
• Results First Submitted: January 24, 2013
• Results First Posted: February 10, 2015
• Last Update Posted: February 10, 2015