GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT00293423
• Collaborator: National Cancer Institute (NCI) (NIH), Agenus Inc. (Industry), American Brain Tumor Association (Other)
• Enrollment: 96
• Locations: 3
• Arms: 2
• Actual Duration (Months): 85.8
• Patients Per Site: 32
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Vaccines made from a person's tumor cells, such as gp96 heat shock protein-peptide complex, may help the body build an effective immune response to kill tumor cells. This phase I/II trial is studying the side effects and best dose of gp96 heat shock protein-peptide complex vaccine to see how well it works in treating patients with recurrent or progressive high-grade glioma over time.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Biological: HSPPC-96; Procedure: Standard Surgical Resection	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

• Phase 1: [closed to accrual as of 7/25/2007]: Determine the safety and best tolerated dose and frequency of gp96 heat shock protein-peptide complex vaccine in patients with recurrent or progressive high-grade glioma.

• Phase 2: Determine the clinical response to treatment, time to disease recurrence and progression, and overall survival of patients treated with this vaccine.

SECONDARY OBJECTIVES:

• Determine the immune response in patients treated with this vaccine.

• Determine survival outcomes in patients treated with this vaccine.

OUTLINE: This is a dose-escalation, phase I study (closed to accrual as of 7/25/2007) followed by a phase II study.

PHASE I [closed to accrual as of 7/25/2007]:

Patients underwent surgical resection. Viable tumor tissue is used to generate the gp96 heat shock protein-peptide complex (HSPPC-96) vaccine. Patients with primary disease receive standard adjuvant therapy after surgery. Patients whose disease progresses during or after standard adjuvant therapy receive the HSPPC-96 vaccine. Patients with recurrent disease receive the HSPPC-96 vaccine between 2-8 weeks after surgery. The HSPPC-96 vaccine is administered intradermally every 1-3 weeks for at least 4 doses and then every 2-3 weeks thereafter in the absence of disease progression, unacceptable toxicity, or vaccine depletion. Cohorts of 6 patients received the HSPPC-96 vaccine at escalating dose frequencies until the maximum tolerated dose (MTD) was determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experienced a dose-limiting toxicity.

PHASE II: Patients received the HSPPC-96 vaccine as in phase I at the appropriate dose frequency determined in phase I (closed to accrual as of 7/25/2007). The HSPPC-96 vaccine is administered intradermally every 1-3 weeks for at least 4 doses and then every 2 weeks thereafter in the absence of disease progression, unacceptable toxicity, or vaccine depletion. After completion of study treatment, patients are followed periodically until death, lost to follow-up, or end of study.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine for Patients With Recurrent High Grade Glioma
• Actual Study Start Date: Nov 18, 2005
• Actual Primary Completion Date: Jan 12, 2013
• Actual Study Completion Date: Jan 12, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: Vaccine Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections.	Biological: HSPPC-96; 25 mcg; Other Names: Heat Shock Glycoprotein 96 Gp96 ; Procedure: Standard Surgical Resection; Patients will undergo standard surgical resection of intracranial tumor; Other Names: Craniotomy
Experimental: Phase 2: Vaccine Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.	Biological: HSPPC-96; 25 mcg; Other Names: Heat Shock Glycoprotein 96 Gp96 ; Procedure: Standard Surgical Resection; Patients will undergo standard surgical resection of intracranial tumor; Other Names: Craniotomy

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) (Phase 1) [Up to 4 weeks]

   MTD determination will be based on the occurrence of dose-limiting toxicities. The MTD will be 1 dose below the dose that defined the dose-limiting toxicities

2. Frequency of gp96 Heat Shock Protein-peptide Complex Vaccine (Phase 1) [Up to 6 months]

   The frequency of dosing of the first 4 injections to be recommended for Phase 2 will be determined by reviewing the reported number of dose-limiting toxicities for weekly or bi-weekly injections.

3. Number of Participants With Dose Limiting Toxicities (Phase 1) [Up to 4 weeks]

   Systemic toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Dose-limiting toxicity is defined as any of the following that are attributable to vaccine therapy: Any grade 3, 4 or 5 toxicity, Any grade >=2 clinical autoimmunity with the potential to threaten critical organs (including lungs, heart, kidney, bowel, bone marrow, liver or central nervous system (CNS), or eyes), and any removal of a patient from therapy due to toxicity

4. Median Progression-free Survival at 6 Months (Phase 2) [6 months]

5. Percentage of Participants With Progression-free Survival at 12 Months (Phase 2) [Up to 12 months]

   Defined as the percentage of participants with confirmed response and who have not progressed from date of surgical resection until death or censored at 12 months

Secondary Outcome Measures

1. Number of Patients With an Immunological Response (Phase 1) [Up to 12 months]

   An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range

2. Number of Patients With an Immunological Response (Phase 2) [Up to 2 years]

   An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range

3. Number of Participants With Grade 3 or Higher, Vaccine Treatment-Related Adverse Events by Toxicity (Phase 2) [Up to 2 years]

   Vaccine treatment-related Adverse Events with a grade >=3 according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be reported.

4. Median Overall Survival (Phase 2) [Up to 2 years]

   Overall survival is defined as the length of time from date of surgical resection until death or censored at end of study period

5. Percentage of Participants Surviving at 6 Months (Phase 2) [Up to 6 months]

   Defined as the percentage of participants still alive from date of surgical resection until death or censored at 6 months

6. Percentage of Participants Surviving at 12 Months (Phase 2) [Up to 12 months]

   Defined as the percentage of participants still alive from date of surgical resection until death or censored at 12 months

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant recurrent glioma*, including any of the following:

• Glioblastoma

• Glioblastoma multiforme

• Recurrent disease or progressive primary disease

• Surgically accessible tumor for which surgical resection is indicated and has not been previously irradiated

• Prior radiotherapy required

• No prior oncophage therapy or immunotherapy for glioma

PATIENT CHARACTERISTICS:

• Karnofsky performance status 80-100%

• Life expectancy ≥ 8 weeks

• Absolute granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Alkaline phosphatase and serum glutamic-pyruvic transaminase (SGPT) <=2.5 times normal

• Bilirubin < 1.5 mg/dL

• Blood Urea Nitrogen (BUN) < 1.5 times normal OR creatinine < 1.5 times normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for at least 4 weeks after completion of study treatment

• No uncontrolled active infection

• No bleeding diathesis

• No psychiatric or medical situation that would preclude study compliance

• No unstable or severe concurrent medical condition

• No other cancer or concurrent malignancy within the past 5 years except adequately treated nonmetastatic in situ carcinoma of the uterine cervix, nonmetastatic nonmelanoma skin cancer, or in complete remission and off all therapy for that disease

• No systemic autoimmune disease (e.g., Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 weeks since prior vincristine

• At least 6 weeks since prior nitrosoureas

• At least 4 weeks since prior temozolomide or other cytotoxic chemotherapy

• At least 4 weeks since prior investigational agents

• At least 1 week since prior noncytotoxic agents

• At least 3 weeks since prior procarbazine

• No radiotherapy within the past 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Columbia University	New York	New York	United States	10032
3	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• University of California, San Francisco
• National Cancer Institute (NCI)
• Agenus Inc.
• American Brain Tumor Association

Investigators

• Study Chair: Jennifer Clarke, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

• Crane CA, Han SJ, Ahn B, Oehlke J, Kivett V, Fedoroff A, Butowski N, Chang SM, Clarke J, Berger MS, McDermott MW, Prados MD, Parsa AT. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res. 2013 Jan 1;19(1):205-14. doi: 10.1158/1078-0432.CCR-11-3358. Epub 2012 Aug 7.

• Responsible Party: Orin Bloch, MD, Principal Investigator, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00293423
• Other Study ID Numbers: 05103; UCSF-H41995-27311-01; NCI-2011-01231; P50CA097257-06; R01CA164714-02
• First Posted: Feb 17, 2006
• Last Update Posted: May 13, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Orin Bloch, MD, Principal Investigator, University of California, San Francisco: adult glioblastoma; recurrent adult brain tumor
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; polysaccharide-K

Study Results

Participant Flow

Recruitment Details	Phase 1 Recruitment took place between August 11, 2005 and July 25, 2007 for participants scheduled for gross total resection of recurrent Glioblastoma multiforme (GBM) Phase 2 Recruitment took place between October 3, 2007 and October 24, 2011 for participants scheduled for gross total resection of recurrent Glioblastoma multiforme (GBM)

Arm/Group Title	Phase 1: Vaccine	Phase 2: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections.	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Period Title: Surgical Resection
STARTED	28	68
COMPLETED	12	41
NOT COMPLETED	16	27
Period Title: Surgical Resection
STARTED	12	41
COMPLETED	12	38
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Phase 1: Vaccine	Phase 2: Vaccine	Total
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections.	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.	Total of all reporting groups
Overall Participants	28	68	96
Age, Customized (Count of Participants)
20-29 years old	0 0%	3 4.4%	3 3.1%
30-39 years old	3 10.7%	2 2.9%	5 5.2%
40-49 years old	5 17.9%	14 20.6%	19 19.8%
50-59 years old	12 42.9%	23 33.8%	35 36.5%
60-69 years old	6 21.4%	20 29.4%	26 27.1%
70-79 years old	2 7.1%	6 8.8%	8 8.3%
Sex: Female, Male (Count of Participants)
Female	13 46.4%	19 27.9%	32 33.3%
Male	15 53.6%	49 72.1%	64 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	28 100%	68 100%	96 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 2.9%	2 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.6%	1 1.5%	2 2.1%
White	27 96.4%	65 95.6%	92 95.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%	68 100%	96 100%
Median Number of Vaccine Doses Administered (vaccine injections) [Median (Full Range) ]
Median (Full Range) [vaccine injections]	6	6	6

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) (Phase 1)
Description	MTD determination will be based on the occurrence of dose-limiting toxicities. The MTD will be 1 dose below the dose that defined the dose-limiting toxicities
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections
Measure Participants	12
Number [micrograms]	25

2. Primary Outcome

Title	Frequency of gp96 Heat Shock Protein-peptide Complex Vaccine (Phase 1)
Description	The frequency of dosing of the first 4 injections to be recommended for Phase 2 will be determined by reviewing the reported number of dose-limiting toxicities for weekly or bi-weekly injections.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections
Measure Participants	12
Number [weeks between doses]	2

3. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (Phase 1)
Description	Systemic toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Dose-limiting toxicity is defined as any of the following that are attributable to vaccine therapy: Any grade 3, 4 or 5 toxicity, Any grade >=2 clinical autoimmunity with the potential to threaten critical organs (including lungs, heart, kidney, bowel, bone marrow, liver or central nervous system (CNS), or eyes), and any removal of a patient from therapy due to toxicity
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections
Measure Participants	12
Count of Participants [Participants]	0 0%

4. Primary Outcome

Title	Median Progression-free Survival at 6 Months (Phase 2)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	41
Median (95% Confidence Interval) [weeks]	19.1

5. Primary Outcome

Title	Percentage of Participants With Progression-free Survival at 12 Months (Phase 2)
Description	Defined as the percentage of participants with confirmed response and who have not progressed from date of surgical resection until death or censored at 12 months
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	41
Number (95% Confidence Interval) [percentage of participants]	29.3 104.6%

6. Secondary Outcome

Title	Number of Patients With an Immunological Response (Phase 1)
Description	An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 1: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections
Measure Participants	12
Number [participants]	11 39.3%

7. Secondary Outcome

Title	Number of Patients With an Immunological Response (Phase 2)
Description	An immunological response is defined as an absolute lymphocyte count (ALC) less than the lower limit of normal (1.0 × 109cells/L), according to the standard laboratory reference range
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	41
Count of Participants [Participants]	27 96.4%

8. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher, Vaccine Treatment-Related Adverse Events by Toxicity (Phase 2)
Description	Vaccine treatment-related Adverse Events with a grade >=3 according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 will be reported.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	41
Number [participants]	1 3.6%

9. Secondary Outcome

Title	Median Overall Survival (Phase 2)
Description	Overall survival is defined as the length of time from date of surgical resection until death or censored at end of study period
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	38
Median (95% Confidence Interval) [weeks]	42.6

10. Secondary Outcome

Title	Percentage of Participants Surviving at 6 Months (Phase 2)
Description	Defined as the percentage of participants still alive from date of surgical resection until death or censored at 6 months
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	90.2 322.1%

11. Secondary Outcome

Title	Percentage of Participants Surviving at 12 Months (Phase 2)
Description	Defined as the percentage of participants still alive from date of surgical resection until death or censored at 12 months
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Vaccine
Arm/Group Description	Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
Measure Participants	38
Number (95% Confidence Interval) [percentage of participants]	29.3 104.6%

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Phase 1: Vaccine		Phase 2: Vaccine
Arm/Group Description	Patients received 25 micrograms of HSPPC-96 bi-weekly or weekly for the first 4 vaccinations followed by biweekly injections.		Treatment consisted of 25 mcg of HSPPC-96 weekly for at least 4 weeks, followed by biweekly injections (pending vaccine availability) for up to 52 weeks from the date of surgical resection.
All Cause Mortality
	Phase 1: Vaccine		Phase 2: Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		39/41 (95.1%)
Serious Adverse Events
	Phase 1: Vaccine		Phase 2: Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		8/41 (19.5%)
Blood and lymphatic system disorders
Thrombocytopenia	0/12 (0%)		1/41 (2.4%)
General disorders
Fatigue	0/12 (0%)		1/41 (2.4%)
Infections and infestations
Wound	0/12 (0%)		1/41 (2.4%)
Skin Infection (Cellulitis)	0/12 (0%)		1/41 (2.4%)
Infections and infestations - Other, Appendix	0/12 (0%)		1/41 (2.4%)
Nervous system disorders
Neurology - Other	0/12 (0%)		1/41 (2.4%)
Seizure	0/12 (0%)		1/41 (2.4%)
Hydrocephalus	0/12 (0%)		1/41 (2.4%)
Peripheral Motor Neuropathy	0/12 (0%)		1/41 (2.4%)
Psychiatric disorders
Psychiatric disorders - Other	0/12 (0%)		1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Phase 1: Vaccine		Phase 2: Vaccine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		41/41 (100%)
Blood and lymphatic system disorders
Lymphatic	2/12 (16.7%)	2	5/41 (12.2%)	5
Leukopenia	4/12 (33.3%)	9	10/41 (24.4%)	10
Coagulopathy	0/12 (0%)	0	3/41 (7.3%)	3
Anemia	0/12 (0%)	0	5/41 (12.2%)	5
Ear and labyrinth disorders
Auditory/Ear - Other	1/12 (8.3%)	1	0/41 (0%)	0
Eye disorders
Ocular/Visual - Other	1/12 (8.3%)	1	0/41 (0%)	0
Gastrointestinal disorders
Gastrointestinal	4/12 (33.3%)	12	14/41 (34.1%)	14
General disorders
Cognitive	2/12 (16.7%)	2	20/41 (48.8%)	20
Fever	0/12 (0%)	0	4/41 (9.8%)	4
Fatigue	7/12 (58.3%)	10	12/41 (29.3%)	12
Anorexia	1/12 (8.3%)	2	4/41 (9.8%)	4
Infections and infestations
Infection	1/12 (8.3%)	1	11/41 (26.8%)	11
Injury, poisoning and procedural complications
Cerebrospinal fluid leak	0/12 (0%)	0	1/41 (2.4%)	1
Investigations
Focal deficit	0/12 (0%)	0	28/41 (68.3%)	28
Injection site reaction	6/12 (50%)	9	17/41 (41.5%)	17
Metabolism and nutrition disorders
Metabolic	9/12 (75%)	32	16/41 (39%)	16
Musculoskeletal and connective tissue disorders
Musculoskeletal	5/12 (41.7%)	8	9/41 (22%)	9
Nervous system disorders
Seizure	4/12 (33.3%)	9	6/41 (14.6%)	6
Hydrocephalus	0/12 (0%)	0	3/41 (7.3%)	3
Psychiatric disorders
Mood	1/12 (8.3%)	1	7/41 (17.1%)	7
Renal and urinary disorders
Genitourinary/renal	2/12 (16.7%)	2	8/41 (19.5%)	8
Respiratory, thoracic and mediastinal disorders
Pulmonary	2/12 (16.7%)	3	6/41 (14.6%)	6
Skin and subcutaneous tissue disorders
Pruritus	0/12 (0%)	0	4/41 (9.8%)	4
Rash	1/12 (8.3%)	1	5/41 (12.2%)	5
Vascular disorders
Vascular	0/12 (0%)	0	3/41 (7.3%)	41
Hematoma	0/12 (0%)	0	3/41 (7.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.