Study of PRO 140 by Subcutaneous Administration in Adult Subjects With HIV -1 Infection

• Sponsor: CytoDyn, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00642707
• Collaborator: (none)
• Enrollment: 44
• Location: 1
• Arms: 4
• Duration (Months): 8
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

The purpose of this study is:

1. To assess the antiviral activity of PRO 140

2. To assess the safety and tolerability of PRO 140

3. To generate additional PK, PD and safety data of PRO 140

Condition or Disease	Intervention/Treatment	Phase
HIV -1 Infection; HIV Infections	Drug: PRO 140 (humanized monoclonal antibody to CCR5); Drug: Placebo Comparator	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Randomized, Double-blind, Placebo Controlled Study of PRO 140 by Subcutaneous Administration in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 PRO 140 for three single SC doses: Days 1, 8, and 15	Drug: PRO 140 (humanized monoclonal antibody to CCR5)
Active Comparator: Arm 2 PRO 140 for three single SC doses: Days 1, 8 and 15	Drug: PRO 140 (humanized monoclonal antibody to CCR5)
Active Comparator: Arm 3 PRO 140 for two single SC doses: Days 1 and 15 plus one SC dose of PBO at Day 8	Drug: PRO 140 (humanized monoclonal antibody to CCR5)
Placebo Comparator: Arm 4 PBO for three single SC doses: Days 1, 8 and 15	Drug: Placebo Comparator

Outcome Measures

Primary Outcome Measures

1. Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL). [59 days]

   The primary end point was the maximum change from baseline in viral load following initiation of treatment, defined as HIV-1 copies/mL, measured by the Roche Amplicor HIV-1 Monitor UltraSensitive™ Test (lower limit of detection [LLD] = 48 copies/mL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males & females, age ≥ 18 years (or minimum adult age as determined by local regulatory authorities)

2. Screening plasma HIV-1 RNA ≥ 5,000 copies/mL

3. CD4+ lymphocyte cell count ≥ 300 cells/mm3 and no documented count < or = 250 cells/mm3

4. Has not taken any antiretroviral therapy (ART) w/in 12 wks of Early Screening Visit

5. Exclusive CCR5-tropic virus as determined by Trofile™ Assay at Early Screening Visit

6. Clinically normal or "not clinically significant (NCS)" resting electrocardiogram

7. Women of reproductive potential must have a negative serum pregnancy test at Late Screening Visit & a negative urine pregnancy test w/in 72 hrs prior to first dose of study medication, & be non-lactating. Male & female subjects must agree not to participate in a conception process from Early Screening Visit through Day 59.

Exclusion Criteria:

1. CXCR4 tropic virus or dual/mixed tropic (R5X4) virus determined by the Trofile™ Assay.

2. Females who are pregnant, lactating or breastfeeding, or who plan to become pregnant during the study.

3. History of active hepatitis within the previous 24 wks

4. Prior use of any entry, attachment, CCR5 co-receptor or fusion inhibitor, including PRO 140, experimental or approved.

5. Any immunization or vaccination (including influenza vaccine) within 30 days prior to administration of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Progenics Pharmaceuticals, Inc.	Tarrytown	New York	United States	10591

Sponsors and Collaborators

• CytoDyn, Inc.

Investigators

• Study Director: Stephen Morris, MD, PhD, Progenics Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: CytoDyn, Inc.
• ClinicalTrials.gov Identifier: NCT00642707
• Other Study ID Numbers: PRO 140 2101
• First Posted: Mar 25, 2008
• Last Update Posted: Jan 14, 2016
• Last Verified: Dec 1, 2015

• Keywords provided by CytoDyn, Inc.: HIV; Treatment Naïve
• Additional relevant MeSH terms: Infections; Communicable Diseases; Leronlimab; Antibodies; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	Recruitment started March 2008 and ended November 2008
Pre-assignment Detail	There was a screening period of up to 12 weeks. Subjects had to be infected with CCR5-tropic human immunodeficiency virus type 1 (HIV-1)or they were excluded from the study.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	PRO 140 - 162 mg for three single SC doses: Days 1, 8, and 15	PRO 140 - 324 mg for three single SC doses: Days 1, 8 and 15	PRO 140 - 324 mg for two single SC doses: Days 1 and 15 plus one SC dose of placebo at Day 8	Placebo for three single SC doses: Days 1, 8 and 15
Period Title: Overall Study
STARTED	11	11	12	10
COMPLETED	10	11	12	8
NOT COMPLETED	1	0	0	2

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4	Total
Arm/Group Description	PRO 140 - 162 mg for three single SC doses: Days 1, 8, and 15	PRO 140 - 324 mg for three single SC doses: Days 1, 8 and 15	PRO 140 - 324 mg for two single SC doses: Days 1 and 15 plus one SC dose of placebo at Day 8	Placebo for three single SC doses: Days 1, 8 and 15	Total of all reporting groups
Overall Participants	11	11	12	10	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	11 100%	12 100%	10 100%	44 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.5 (5.13)	41.9 (5.46)	46.4 (8.18)	42.4 (7.44)	42.4 (7.09)
Sex: Female, Male (Count of Participants)
Female	1 9.1%	1 9.1%	1 8.3%	1 10%	4 9.1%
Male	10 90.9%	10 90.9%	11 91.7%	9 90%	40 90.9%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	12 100%	10 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Change in Viral Load Following Initiation of Treatment (Viral Load is Defined as HIV-1 Copies/mL and Expressed as log10 Copies/mL).
Description	The primary end point was the maximum change from baseline in viral load following initiation of treatment, defined as HIV-1 copies/mL, measured by the Roche Amplicor HIV-1 Monitor UltraSensitive™ Test (lower limit of detection [LLD] = 48 copies/mL).
Time Frame	59 days

Outcome Measure Data

Analysis Population Description

All randomized subjects who received one dose of study drug were considered intent-to-treat (ITT) subjects and were analyzed for efficacy.

Arm/Group Title	Arm 1	Arm 2	Arm 3	Arm 4
Arm/Group Description	PRO 140 - 162 mg for three single SC doses: Days 1, 8, and 15	PRO 140 - 324 mg for three single SC doses: Days 1, 8 and 15	PRO 140 - 324 mg for two single SC doses: Days 1 and 15 plus one SC dose of placebo at Day 8	Placebo for three single SC doses: Days 1, 8 and 15
Measure Participants	11	11	12	10
Mean (Standard Deviation) [Log10copies/HIV-1 RNA/mL]	-0.99 (0.558)	-1.65 (0.571)	-1.37 (0.891)	-0.23 (0.285)

Adverse Events

Arm/Group Title	Arm 1		Arm 2		Arm 3		Arm 4
Arm/Group Description	PRO 140 - 162 mg for three single SC doses: Days 1, 8, and 15		PRO 140 - 324 mg for three single SC doses: Days 1, 8 and 15		PRO 140 - 324 mg for two single SC doses: Days 1 and 15 plus one SC dose of placebo at Day 8		Placebo for three single SC doses: Days 1, 8 and 15
All Cause Mortality
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)		3/12 (25%)		0/10 (0%)
Infections and infestations
Meningitis viral	0/11 (0%)	0	0/11 (0%)	0	1/1 (100%)	1	0/10 (0%)	0
Scrotal abscess	0/11 (0%)	0	0/11 (0%)	0	1/1 (100%)	1	0/10 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer stage I	0/11 (0%)	0	0/11 (0%)	0	1/1 (100%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1		Arm 2		Arm 3		Arm 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		10/11 (90.9%)		11/12 (91.7%)		10/10 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	3/11 (27.3%)	4	1/11 (9.1%)	1	1/12 (8.3%)	1	0/10 (0%)	0
Cardiac disorders
Tachycardia	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	2/10 (20%)	2
Ear and labyrinth disorders
Ear pain	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Tympanic membrane disorder	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Gastrointestinal disorders
Constipation	1/11 (9.1%)	1	1/11 (9.1%)	1	1/12 (8.3%)	1	0/10 (0%)	0
Dental discomfort	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Diarrhoea	1/11 (9.1%)	1	3/11 (27.3%)	3	2/12 (16.7%)	2	0/10 (0%)	0
Faeces pale	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Flatulence	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Gastritis	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Intestinal mass	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Nausea	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/10 (0%)	0
Perianal erythema	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Toothache	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
General disorders
Adverse drug reaction	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Asthenia	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Chills	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Fatigue	2/11 (18.2%)	2	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Infusion site erythema	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Infusion site induration	1/11 (9.1%)	3	2/11 (18.2%)	5	3/12 (25%)	5	0/10 (0%)	0
Infusion site inflammation	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Infusion site pain	0/11 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	4	1/10 (10%)	1
Injection site discomfort	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Injection site erythema	2/11 (18.2%)	5	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Injection site haemorrhage	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Injection site induration	2/11 (18.2%)	5	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Injection site irritation	1/11 (9.1%)	1	1/11 (9.1%)	2	1/12 (8.3%)	1	0/10 (0%)	0
Injection site pain	1/11 (9.1%)	3	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Injection site reaction	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/10 (10%)	1
Pain	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/10 (10%)	1
Pyrexia	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Vessel puncture site haematoma	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Infections and infestations
Chlamydial infection	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Folliculitis	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Gastroenteritis	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Herpes simplex	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Influenza	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Meningitis viral	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Nasopharyngitis	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	2	0/10 (0%)	0
Oral herpes	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Respiratory tract infection viral	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Scrotal abscess	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	4	0/10 (0%)	0
Skin infection	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Staphylococcal infection	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Subcutaneous abcess	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Syphillis	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Tinea cruris	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Upper respiratory tract infection	0/11 (0%)	0	2/11 (18.2%)	2	1/12 (8.3%)	1	0/10 (0%)	0
Urethritis gonococcal	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Vaginitis bacterial	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	2/10 (20%)	3
Chemical poisoning	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Excoriation	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Investigations
Blood creatine phosphokinase increased	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Blood pressure diastolic increased	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Blood pressure increased	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	5	0/10 (0%)	0
Cardiac murmur	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Electrocardiogram abnormal	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Herpes simplex serology positive	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Urine analysis abnormal	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Weight increased	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Metabolism and nutrition disorders
Anorexia	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	3	0/10 (0%)	0
Increased appetite	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Clubbing	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Musculoskeletal pain	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Myalgia	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/10 (0%)	0
Pain in extremity	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	3	0/10 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer stage I	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Lipoma	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Uterine leiomyoma	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Nervous system disorders
Anaesthesia	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Dizziness	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Headache	3/11 (27.3%)	3	0/11 (0%)	0	2/12 (16.7%)	2	1/10 (10%)	2
Sinus headache	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Psychiatric disorders
Abnormal dreams	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Depression	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Drug abuse	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Insomnia	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/10 (0%)	0
Stress	0/11 (0%)	0	1/11 (9.1%)	1	0/0 (NaN)	0	0/10 (0%)	0
Renal and urinary disorders
Chromaturia	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Penile discharge	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Scrotal pain	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	2	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Nasal congestion	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Nasal oedema	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/10 (0%)	0
Rhinitis allergic	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Dermatitis	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/10 (0%)	0
Dry skin	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Pruritus	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Rash	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Skin hyperpigmentation	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Skin maceration	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Urticaria	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/10 (0%)	0
Vascular disorders
Haematoma	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/10 (10%)	1
Hypertension	0/11 (0%)	0	1/11 (9.1%)	2	1/12 (8.3%)	1	2/10 (20%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Because the study is a multicenter study, the PI(s) can only publish after the aggregate results of all investigators and institutions participating in the study have been published, and the proposed publication is reviewed by Progenics. In the event that Progenics does not publish the results of the study within eighteen months from availability of final study analysis, the PI can publish provided that the proposed publication is reviewed by Progenics.