TH9507 Extension Study in Patients With HIV- Associated Lipodystrophy

• Sponsor: Theratechnologies (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00608023
• Collaborator: (none)
• Enrollment: 263
• Locations: 49
• Arms: 3
• Duration (Months): 14
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Assessing the Efficacy and Long-Term Safety of a 2 mg dose of TH9507, a Growth Hormone-Releasing Factor Analog, in HIV Subjects with Excess Abdominal Fat Accumulation

Condition or Disease	Intervention/Treatment	Phase
Lipodystrophy; HIV Infections	Drug: Tesamorelin; Drug: Placebo for Tesamorelin	Phase 3

Detailed Description

HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation, loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from the first Phase 3 multicenter, randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV- infected patients with excess of abdominal fat accumulation for 26 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with lesser changes in limb fat and subcutaneous adipose tissue (SAT). The present study is aimed at confirming the observations made during the first Phase 3 study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 263 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Extension Study Assessing the Efficacy and Long-term Safety of a 2 mg Dose of TH9507, a GHRH Analog, in HIV Subjects With Excess Abdominal Fat Accumulation
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tesamorelin 12 months (T-T) Tesamorelin 2 mg/day for 12 months	Drug: Tesamorelin; Other Names: Egrifta
Experimental: Tesamorelin-Placebo (T-P) Tesamorelin 2 mg/day for 6 months - Placebo for 6 months	Drug: Tesamorelin; Other Names: Egrifta ; Drug: Placebo for Tesamorelin
Experimental: Placebo-Tesamorelin (P-T) Placebo 6 months - Tesamorelin 2 mg/day for 6 months	Drug: Tesamorelin; Other Names: Egrifta ; Drug: Placebo for Tesamorelin

Outcome Measures

Primary Outcome Measures

1. Changes From Baseline in Fasting Blood Glucose at Week 52 [Baseline and Week 52]

   Blood glucose was determined after an overnight fast. Changes in blood glucose between baseline and Week 52 are reported.

2. Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52 [Baseline and Week 52]

   Glucose tolerance was determined after an overnight fast using standard 75 gram-oral glucose tolerance test (OGTT) with glucose measured at timepoints 0, 30, 60, 90 and 120. Changes in glucose tolerance between baseline and Week 52 are reported.

Secondary Outcome Measures

1. Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52 [Baseline and Week 52]

   Visceral adipose tissue (VAT) was assessed by computerized tomography (CT) scan using a single-slice. Changes in VAT between baseline and Week 52 are reported.

Other Outcome Measures

1. Changes From Baseline in Triglycerides at Week 52 [Baseline and Week 52]

   Blood lipid levels were determined under fasting conditions. Changes in triglycerides between baseline and Week 52 are reported.

2. Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52 [Baseline and Week 52]

   Blood lipid levels were determined under fasting conditions. Total Cholesterol/HDL Cholesterol Ratio was obtained by dividing the total cholesterol value by the value of the HDL cholesterol. Changes between baseline and Week 52 are reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who have completed the 26 weeks treatment period of the TH9507-CTR-1011 study.

• Signed informed consent before any trial-related activities.

Exclusion Criteria:

• Fasting blood glucose >8.33 mmoL (150 mg/dL) at the end of the TH9507-CTR-1011 study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-2170
2	Body Positive Inc.	Phoenix	Arizona	United States	85006
3	Somero, Michael	Indio	California	United States	92201
4	UCLA School of Medicine	Los Angeles	California	United States	90035
5	Office of Dr. Michael Somero	Palm Springs	California	United States	92262
6	University of California	San Francisco	California	United States	94110
7	Kaiser Permanente	San Francisco	California	United States	94118
8	UCSF/VA Medical Center	San Francisco	California	United States	94121
9	AIDS Research Alliance	West Hollywood	California	United States	90069
10	Denver Public Health Department	Denver	Colorado	United States	80204-4507
11	Office of Dr. Gary Richmond	Fort Lauderdale	Florida	United States	33316
12	Hendry/Glades County Health Departments	LaBelle	Florida	United States	33935
13	Infectious Disease Research Institute Inc.	Tampa	Florida	United States	33614
14	AIDS Research Consortium Atlanta (ARCA)	Atlanta	Georgia	United States	30308
15	Northern Healthcare	Chicago	Illinois	United States	60657
16	Northstar Medical	Chicago	Illinois	United States	60657
17	Indiana University Department of Medicine	Indianapolis	Indiana	United States	46202
18	Tufts New England Medical Center	Boston	Massachusetts	United States	02111
19	Tufts University School of Medicine	Boston	Massachusetts	United States	02111
20	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
21	The Research Institute	Springfield	Massachusetts	United States	01107
22	ID Associates	Hillsborough	New Jersey	United States	08844
23	AIDS Community Research Initiative of America	New York	New York	United States	10018
24	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7215
25	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
26	Central Texas Clinical Research	Austin	Texas	United States	78705
27	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75232
28	Swedish Medical Center	Seattle	Washington	United States	98104
29	C. H. U. Sart-Tilman	Liège		Belgium	4000
30	St-Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
31	St. Paul's Hospital	Vancouver	British Columbia	Canada	V6Z 1Y6
32	McMaster University Health Sciences Centre	Hamilton	Ontario	Canada	L8N 3Z5
33	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
34	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
35	Centre Hospitalier Universitaire de Santé de l'Estrie	Fleurimont	Quebec	Canada	J1H 5N4
36	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4
37	Groupe de Recherche en Rhumatologie et maladies osseuses	Ste-Foy	Quebec	Canada	G1V 3M7
38	Hôpital Hotel Dieu Lyon	Lyon Cedex 69		France	69288
39	Hotel Dieu	Nantes Cedex 1		France	44093
40	Hopital Europeen Georges Pompidou	Paris		France	75015
41	Hopital Necker	Paris		France	75743
42	Hosp. Ramon y Cajal	Madrid		Spain	28034
43	Hosp. Clinico San Carlos	Madrid		Spain	28040
44	Hosp.C.U.de Santiago	Santiago de Compostela		Spain	15706
45	BSUH NHS Trust	Brighton		United Kingdom	BN2 1ES
46	St Georges Hospital	London		United Kingdom	17 0QT
47	Royal Free Hospital	London		United Kingdom	NW3 2QG
48	Chelsea and Westminster Hospital	London		United Kingdom	SW10 9TH
49	St Mary's NHS Trust	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Theratechnologies

Investigators

• Principal Investigator: Steven Grinspoon, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Theratechnologies
• ClinicalTrials.gov Identifier: NCT00608023
• Other Study ID Numbers: TH9507-CTR-1012
• First Posted: Feb 6, 2008
• Last Update Posted: May 2, 2022
• Last Verified: Mar 1, 2014

• Keywords provided by Theratechnologies: HIV; Lipodystrophy; Abdominal fat accumulation; Growth hormone releasing hormone; HIV-associated lipodystrophy; Treatment experienced
• Additional relevant MeSH terms: Lipodystrophy; Tesamorelin; Growth Hormone-Releasing Hormone

Study Results

Participant Flow

Arm/Group Title	Tesamorelin (52 Weeks)	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo-Tesamorelin (P-T)
Arm/Group Description	Tesamorelin 2 mg/day for 52 Weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
Period Title: Overall Study
STARTED	92	85	86
COMPLETED	80	63	72
NOT COMPLETED	12	22	14

Baseline Characteristics

Arm/Group Title	Tesamorelin 52 Weeks	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)	Total
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks	Total of all reporting groups
Overall Participants	92	85	86	263
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.7 (6.9)	48.9 (7.2)	48.4 (7.9)	48.3 (7.3)
Sex: Female, Male (Count of Participants)
Female	9 9.8%	9 10.6%	11 12.8%	29 11%
Male	83 90.2%	76 89.4%	75 87.2%	234 89%

Outcome Measures

1. Secondary Outcome

Title	Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52
Description	Visceral adipose tissue (VAT) was assessed by computerized tomography (CT) scan using a single-slice. Changes in VAT between baseline and Week 52 are reported.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

All data were included in the analysis by intention to treat principles. Intent to treat populations were defined as all randomized subjects who were exposed to study drug (i.e injection of at least 1 dose of study drug).

Arm/Group Title	Tesamorelin 52 Weeks	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
Measure Participants	92	85	86
Mean (Standard Deviation) [cm^2]	-41 (57)	0 (53)	-26 (47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tesamorelin 52 Weeks, Tesamorelin (26 Weeks) - Placebo (26 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments

2. Other Pre-specified Outcome

Title	Changes From Baseline in Triglycerides at Week 52
Description	Blood lipid levels were determined under fasting conditions. Changes in triglycerides between baseline and Week 52 are reported.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tesamorelin (52 Weeks)	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks.	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks.
Measure Participants	92	85	86
Mean (Standard Deviation) [mg/dL]	-37 (196)	4 (177)	1 (120)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tesamorelin 52 Weeks, Tesamorelin (26 Weeks) - Placebo (26 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments

3. Other Pre-specified Outcome

Title	Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52
Description	Blood lipid levels were determined under fasting conditions. Total Cholesterol/HDL Cholesterol Ratio was obtained by dividing the total cholesterol value by the value of the HDL cholesterol. Changes between baseline and Week 52 are reported.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tesamorelin 52 Weeks	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
Measure Participants	92	85	86
Mean (Standard Deviation) [ratio]	-0.23 (1.75)	0.13 (1.19)	0.06 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tesamorelin 52 Weeks, Tesamorelin (26 Weeks) - Placebo (26 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments

4. Primary Outcome

Title	Changes From Baseline in Fasting Blood Glucose at Week 52
Description	Blood glucose was determined after an overnight fast. Changes in blood glucose between baseline and Week 52 are reported.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tesamorelin 52 Weeks	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
Measure Participants	92	85	86
Mean (Standard Deviation) [mg/dL]	0 (16)	-2 (34)	1 (21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tesamorelin 52 Weeks, Tesamorelin (26 Weeks) - Placebo (26 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments

5. Primary Outcome

Title	Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52
Description	Glucose tolerance was determined after an overnight fast using standard 75 gram-oral glucose tolerance test (OGTT) with glucose measured at timepoints 0, 30, 60, 90 and 120. Changes in glucose tolerance between baseline and Week 52 are reported.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tesamorelin 52 Weeks	Tesamorelin (26 Weeks) - Placebo (26 Weeks)	Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks	Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks	Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
Measure Participants	92	85	86
Mean (Standard Deviation) [mg/dL]	-2 (38)	2 (35)	7 (37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tesamorelin 52 Weeks, Tesamorelin (26 Weeks) - Placebo (26 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Tesamorelin 52 Weeks		Tesamorelin (26 Weeks) - Placebo (26 Weeks)		Placebo (26 Weeks) - Tesamorelin (26 Weeks)
Arm/Group Description	Tesamorelin 2 mg/day for 52 weeks		Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks		Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks
All Cause Mortality
	Tesamorelin 52 Weeks		Tesamorelin (26 Weeks) - Placebo (26 Weeks)		Placebo (26 Weeks) - Tesamorelin (26 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Tesamorelin 52 Weeks		Tesamorelin (26 Weeks) - Placebo (26 Weeks)		Placebo (26 Weeks) - Tesamorelin (26 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/92 (3.3%)		1/85 (1.2%)		3/86 (3.5%)
Eye disorders
Retinopathy	1/92 (1.1%)		0/85 (0%)		0/86 (0%)
Gastrointestinal disorders
Abdominal pain	0/92 (0%)		1/85 (1.2%)		0/86 (0%)
General disorders
Chest pain	1/92 (1.1%)		0/85 (0%)		0/86 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin disease	0/92 (0%)		0/85 (0%)		1/86 (1.2%)
Psychiatric disorders
Mental status changes	1/92 (1.1%)		0/85 (0%)		0/86 (0%)
Renal and urinary disorders
Nephrolithiasis	0/92 (0%)		0/85 (0%)		1/86 (1.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/92 (0%)		0/85 (0%)		1/86 (1.2%)
Other (Not Including Serious) Adverse Events
	Tesamorelin 52 Weeks		Tesamorelin (26 Weeks) - Placebo (26 Weeks)		Placebo (26 Weeks) - Tesamorelin (26 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/92 (18.5%)		11/85 (12.9%)		28/86 (32.6%)
Gastrointestinal disorders
Diarrhoea	3/92 (3.3%)		4/85 (4.7%)		5/86 (5.8%)
General disorders
Injection site erythema	3/92 (3.3%)		0/85 (0%)		5/86 (5.8%)
Injection site pain	0/92 (0%)		0/85 (0%)		5/86 (5.8%)
Musculoskeletal and connective tissue disorders
Musculosketal stiffness	1/92 (1.1%)		0/85 (0%)		5/86 (5.8%)
Nervous system disorders
Paresthesia	2/92 (2.2%)		3/85 (3.5%)		5/86 (5.8%)
Psychiatric disorders
Insomnia	0/92 (0%)		0/85 (0%)		5/86 (5.8%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection	8/92 (8.7%)		4/85 (4.7%)		3/86 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.