HIV Infections, Lipodystrophy
Conditions
Keywords
Growth hormone, Serostim®, Human Adipose Redistribution Syndrome, Human Immunodeficiency Virus lipodystrophy
Brief summary
The primary objective of the study is to determine if Serostim® 4 mg administered daily for 12 weeks as treatment for the abnormal fat accumulation and distribution associated with HIV-associated Adipose Redistribution Syndrome (HARS) reduces Visceral Adipose Tissue (VAT, measured by CT scan) more effectively than placebo.
Interventions
DRUGPlacebo
Placebo matched to serostim® as subcutaneous injection.
DRUGSerostim® 4 mg
Serostim® as subcutaneous injection at a maximum dose of 4 milligram (mg) per day based on body weight.
DRUGSerostim® 2 mg
Serostim® 2 mg as subcutaneous injection on alternate days.
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Have written laboratory documentation of an HIV infection by one of the following methods: * Detectable viral load measured by polymerase chain reaction (PCR) amplification, branched chain DNA (bDNA) signal amplification or the presence of p24 antigen. * Presence of HIV antibodies confirmed by either Western blot or immunofluorescence assay. Written laboratory documentation of an HIV infection must be obtained prior to randomization. In the absence of documented historical confirmation, an assay of HIV antibodies will be included in the Screening Laboratory Panel. Results will be confirmed with a Western Blot. 2. Have evidence of excess abdominal adipose deposition when measured by the anthropometric methodology, using the following cut off values: * Men: Waist circumference \>88.2 cm AND waist: hip ratio \>= 0.95. * Women: Waist circumference \>75.3 cm AND waist: hip ratio \>= 0.9. 3. Are taking antiretroviral medication(s) which is (are) approved or is (are) available under a Treatment IND. The regimen must have remained stable for 30 days prior to study entry. Subjects must also agree not to discontinue or to change their regimen for the duration of the study except as judged medically necessary. 4. Have parameter values less than the following limits (using results from the central laboratory): * AST, ALT, and amylase \<= 3 times the upper limit of normal (Screening). * Fasting triglycerides \<= 1,000 mg/dL (Screening). * Fasting glucose \<110 mg/dL (Screening). * Two-hour (120 minute) glucose \<140 mg/dL (Screening). 5. Weight \>= 36 kg (79.3 lb) 6. Be between 18 and 60 years of age (inclusive) unless local law dictates different limits. 7. Sufficiently literate in English to be able to comprehend and complete the Quality of Life Questionnaire. 8. Willing and able to comply with the protocol for the duration of the study. 9. Have voluntarily provided written informed consent (with subject authorization under HIPAA), prior to performing any study-related procedure that is not part of normal medical care, and with the understanding that the subject may withdraw consent at any time without prejudice to future medical care. 10. Female subjects must: 1. Be post menopausal (\>= 1 year) or surgically sterilized (i.e., have undergone tubal ligation or hysterectomy) or 2. Use a contraceptive method for the duration of the study such as: * Hormonal contraceptive * Intra uterine device * Diaphragm with spermicide, or condom with spermicide. And 3. Must be neither pregnant nor breast feeding. 4. Confirmation that female subjects of childbearing potential are not pregnant must be established by a negative beta-hCG serum pregnancy test during the 14-day screening period prior to Study Day 1. If the beta-hCG serum pregnancy test is performed more than 7 days prior to Study Day 1, a urine pregnancy test must be performed by the site laboratory on Study Day 1 to confirm a negative test result.
Exclusion criteria
1. Have an active AIDS-defining opportunistic complication (OC) as defined by the CDC or have had an untreated or suspected serious systemic infection, or have had a persistent fever \>= 101°F (38.3°C) during the 30 days prior to study entry. 2. Any active or past history of malignancy, except for localized cutaneous Kaposi's sarcoma (fewer than 10 lesions, none of which are larger than 2 cm, and not on active therapy). Such exceptions must be confirmed in writing by the Serono Study Director. 3. Have a CNS mass or active CNS process associated with neurological findings. 4. Have unstable or untreated hypertension, defined as \>= 140/90 mm Hg at the time of the Screening Visit, and/or have initiated or changed antihypertensive therapy in the 30 days prior to Study Day 1. 5. Have an acute critical illness treated in an intensive care unit, e.g., due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure. 6. Have a recent history of sleep apnea or intermittent upper respiratory obstruction. 7. Have any condition, which interferes with informed consent or protocol compliance including, but not limited to, active substance abuse and/or dementia. 8. Are unable to comply with the Concomitant Therapy restrictions including: * therapy for obesity including therapy with anorexigenic or fat reducing drugs * anti-diabetic or insulin sensitizing medications * systemic glucocorticoids * systemic chemotherapy, interferon or radiation therapy treatment * androgenic agents including, but not limited to testosterone, nandrolone, oxandrolone, oxymetholone, etc. (testosterone replacement therapy for hypogonadism is the exception to this exclusion and will be allowed if started \> 30 days prior to Study Day 1) * progestational agents, unless used for oral contraception or post-menopausal hormone replacement therapy * appetite stimulants * investigational agents, unless approved in advance by the study medical director. Specifically, experimental antiretroviral agents are disallowed, unless available under a treatment IND or expanded access program (30 days). * Liposuction or other elective plastic surgery * AIDS wasting therapy or prior growth hormone treatment other than study drug (for 12 months prior to the screening visit) 9. Have ever been diagnosed with any of the following conditions: * Pancreatitis * Carpal tunnel syndrome (unless resolved by surgical release) * Diabetes mellitus * Angina pectoris * Coronary artery disease * Any disorder associated with moderate to severe edema (e.g., ascites, nephrotic syndrome, congestive heart failure, lymphedema). 10. Allergy or hypersensitivity to growth hormone. 11. Are participating in any other clinical studies. In order to participate in this trial a subject must meet all of the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Period I: Change From Baseline in Absolute Area of Visceral Adipose Tissue (VAT) at Week 12 | Baseline, Week 12 | Absolute area of VAT was measured by cross-sectional computed tomography (CT) scan at the level of the L4-5 inter-vertebral disk. CT scanning was to be used to assess the cross sectional area of abdominal fat and its distribution between the visceral and subcutaneous compartments, as measured at L4-L5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Period I: Change From Baseline in Trunk Fat at Week 12 | Baseline, Week 12 | Changes in trunk fat was measured as changes in mass (kg) on Dual-Energy X-Ray Absorptiometry (DXA) Scan. |
| Change From Baseline in Patient Reported Outcome of Body Image Distress at Week 12 | Baseline, Week 12 | Body image distress was assessed on a scale ranging from 0 to 100, where 0 = Extremely Upsetting and 100 = Extremely Encouraging. |
| Treatment Period I: Change From Baseline in Non- High-density Lipoprotein (Non-HDL) Cholesterol at Week 12 | Baseline, Week 12 | Lipid profile data was analyzed for Non-HDL Cholesterol. |
| Treatment Period II: Failure Rate at Week 36 Based on Visceral Adipose Tissue (VAT) For Subjects Who Received Serostim® 4 mg in Period I | Week 36 | Failure rate based on VAT was assessed by CT scan at L4-L5. The failure rate was defined as the percentage of subjects who regained \>50% of their VAT lost in Treatment Period I. This outcome was to be assessed for subjects who received Serostim® 4 mg in Period I. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Period I: Placebo Subjects received placebo matched to serostim® as subcutaneous injection daily for a period of 12 weeks. | 79 |
| Period I: Serostim® 4 mg Subjects received Serostim® as subcutaneous injection at a maximum dose of 4 milligram (mg) per day based on body weight for a period of 12 weeks. | 243 |
| Total | 322 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Treatment Period II: Week 12 to Week 36 | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| Treatment Period II: Week 12 to Week 36 | Subjects Did Not Complete Week 36 | 0 | 0 | 15 | 15 | 17 |
| Treatment Period II: Week 12 to Week 36 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
| Treatment Period I (Week 1 to Week 12) | Did not continue to Period II | 1 | 15 | 0 | 0 | 0 |
| Treatment Period I (Week 1 to Week 12) | Subjects Did Not Complete Week 12 | 5 | 43 | 0 | 0 | 0 |
| Treatment Period I (Week 1 to Week 12) | Subjects Did Not Receive Study Drug | 0 | 1 | 0 | 0 | 0 |
| Treatment Period I (Week 1 to Week 12) | Subjects Without Post-Baseline Assessmen | 2 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Period I: Placebo | Period I: Serostim® 4 mg | Total |
|---|---|---|---|
| Age, Continuous | 45.5 Years STANDARD_DEVIATION 7.5 | 44.5 Years STANDARD_DEVIATION 7 | 44.8 Years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 11 Participants | 36 Participants | 47 Participants |
| Sex: Female, Male Male | 68 Participants | 207 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 70 / 81 | 244 / 244 | 46 / 93 | 48 / 92 | 14 / 73 | 73 / 73 |
| serious Total, serious adverse events | 2 / 81 | 3 / 244 | 3 / 93 | 2 / 92 | 2 / 73 | 1 / 73 |
Outcome results
Primary
Treatment Period I: Change From Baseline in Absolute Area of Visceral Adipose Tissue (VAT) at Week 12
Absolute area of VAT was measured by cross-sectional computed tomography (CT) scan at the level of the L4-5 inter-vertebral disk. CT scanning was to be used to assess the cross sectional area of abdominal fat and its distribution between the visceral and subcutaneous compartments, as measured at L4-L5.
Time frame: Baseline, Week 12
Population: The modified ITT Population was defined as all subjects who had a baseline and at least one post-baseline efficacy measurement in treatment period I. Here Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period I: Placebo | Treatment Period I: Change From Baseline in Absolute Area of Visceral Adipose Tissue (VAT) at Week 12 | 0.5 Square Centimeter (cm^2) | Standard Deviation 34.5 |
| Period I: Serostim® 4 mg | Treatment Period I: Change From Baseline in Absolute Area of Visceral Adipose Tissue (VAT) at Week 12 | -32.6 Square Centimeter (cm^2) | Standard Deviation 37.9 |
p-value: <0.001Nonparametric ANCOVA Model
Secondary
Change From Baseline in Patient Reported Outcome of Body Image Distress at Week 12
Body image distress was assessed on a scale ranging from 0 to 100, where 0 = Extremely Upsetting and 100 = Extremely Encouraging.
Time frame: Baseline, Week 12
Population: The modified ITT Population was defined as all subjects who had a baseline and at least one post-baseline efficacy measurement in treatment period I.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period I: Placebo | Change From Baseline in Patient Reported Outcome of Body Image Distress at Week 12 | 0.23 units on a scale | Standard Deviation 1.42 |
| Period I: Serostim® 4 mg | Change From Baseline in Patient Reported Outcome of Body Image Distress at Week 12 | 0.10 units on a scale | Standard Deviation 1.73 |
Secondary
Treatment Period I: Change From Baseline in Non- High-density Lipoprotein (Non-HDL) Cholesterol at Week 12
Lipid profile data was analyzed for Non-HDL Cholesterol.
Time frame: Baseline, Week 12
Population: The modified ITT Population was defined as all subjects who had a baseline and at least one post-baseline efficacy measurement in treatment period I. Here Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period I: Placebo | Treatment Period I: Change From Baseline in Non- High-density Lipoprotein (Non-HDL) Cholesterol at Week 12 | -2.8 milligram/deciliter (mg/dL) | Standard Deviation 28.1 |
| Period I: Serostim® 4 mg | Treatment Period I: Change From Baseline in Non- High-density Lipoprotein (Non-HDL) Cholesterol at Week 12 | -13.0 milligram/deciliter (mg/dL) | Standard Deviation 37.1 |
Secondary
Treatment Period I: Change From Baseline in Trunk Fat at Week 12
Changes in trunk fat was measured as changes in mass (kg) on Dual-Energy X-Ray Absorptiometry (DXA) Scan.
Time frame: Baseline, Week 12
Population: The modified ITT Population was defined as all subjects who had a baseline and at least one post-baseline efficacy measurement in treatment period I. Here Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period I: Placebo | Treatment Period I: Change From Baseline in Trunk Fat at Week 12 | 0.2 Kilogram (Kg) | Standard Deviation 1.3 |
| Period I: Serostim® 4 mg | Treatment Period I: Change From Baseline in Trunk Fat at Week 12 | -2.2 Kilogram (Kg) | Standard Deviation 1.7 |
Secondary
Treatment Period II: Failure Rate at Week 36 Based on Visceral Adipose Tissue (VAT) For Subjects Who Received Serostim® 4 mg in Period I
Failure rate based on VAT was assessed by CT scan at L4-L5. The failure rate was defined as the percentage of subjects who regained \>50% of their VAT lost in Treatment Period I. This outcome was to be assessed for subjects who received Serostim® 4 mg in Period I.
Time frame: Week 36
Population: The modified ITT Population for treatment period II was defined as subjects who were re-randomized into Weeks 12 to 36 of the study and who had at least one post-Week 12 efficacy evaluation. Here Overall Number of Participants Analyzed signifies those subjects who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period I: Placebo | Treatment Period II: Failure Rate at Week 36 Based on Visceral Adipose Tissue (VAT) For Subjects Who Received Serostim® 4 mg in Period I | 53.7 percentage of subjects |
| Period I: Serostim® 4 mg | Treatment Period II: Failure Rate at Week 36 Based on Visceral Adipose Tissue (VAT) For Subjects Who Received Serostim® 4 mg in Period I | 40.3 percentage of subjects |