Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency

• Sponsor: Applied Genetic Technologies Corp (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01054339
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 9
• Locations: 4
• Arms: 3
• Duration (Months): 64
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Assessment of the safety and efficacy of intramuscular (IM) administration of a recombinant adenoassociated virus (rAAV) alpha-1 antitrypsin (AAT) vector (rAAV1-CB-hAAT) in AAT-deficient adults at three dosage levels [6.0 × 10e11, 1.9 × 10e12 and 6.0 × 10e12 vector genome particles (vg) per kg body weight].

Funding Sources - The FDA Office of Orphan Products Development and NIH National Heart, Lung, and Blood Institute

Condition or Disease	Intervention/Treatment	Phase
Alpha-1 Antitrypsin Deficiency	Drug: rAAV1-CB-hAAT	Phase 2

Detailed Description

The study is a non-randomized, open-label, multi-center, sequential, three-arm, Phase 2 clinical trial evaluating the safety and efficacy of administration of a rAAV1-CB-hAAT vector administered by IM injection. Each participant will receive rAAV1-CB-hAAT on a single occasion. Three groups of three subjects each will receive rAAV1-CB-hAAT at dosage levels of 6 x 10e11 vg/kg, 1.9 x 10e12 vg/kg or 6 x 10e12 vg/kg by IM injection. Subjects in group 1 will receive a total of 10 IM injections distributed across a single muscle site, subjects in group 2 will receive a total of 32 IM injections distributed across three muscle sites, and subjects in group 3 will receive 100 IM injections distributed across 10 muscle sites. Each injection will be given in a volume of 1.35 mL, at the appropriate vector concentration to achieve the desired total vector dose.

The three groups were enrolled sequentially, with review of safety data by a Data and Safety Monitoring Board before enrollment of each higher dosage level group.

Safety was monitored by evaluation of adverse events, hematology and clinical chemistry parameters, histological examination of muscle biopsies, and measurement of serum antibodies to AAT. Efficacy was measured by evaluation of serum concentrations of M-specific AAT and total AAT, and serum AAT phenotype determined on isoelectric focusing gels. Additional information collected included presence of the vector in blood or semen, changes in serum anti-AAV antibody titers, and changes in T cell responses to AAV and AAT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multiple-Site, Phase 2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Alpha-1 Antitrypsin (rAAV1-CB-hAAT) in Patients With Alpha-1 Antitrypsin Deficiency
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low dose rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg	Drug: rAAV1-CB-hAAT; Recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin
Experimental: Middle dose rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg	Drug: rAAV1-CB-hAAT; Recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin
Experimental: High dose rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg	Drug: rAAV1-CB-hAAT; Recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin

Outcome Measures

Primary Outcome Measures

1. Frequency of Grade 3 or 4 Adverse Events [During 1 year after study agent administration]

Secondary Outcome Measures

1. Changes in Serum M-specific Alpha-1 Antitrypsin Concentration [During months 6-12 after study agent adminsitration]

   Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 values and mean ± SE for the difference between the pre-treatment and months 6-12 means for 2 subjects in the low dose group and 3 subjects in each of the other two groups. The monoclonal antibody used to determine serum M-specific AAT concentrations has very little cross-reactivity with Z type AAT but cross-reacts strongly with S type AAT, causing results for this assay to be spuriously high for subject 303 in the low dose group.

2. Changes in Serum Total Alpha-1 Antitrypsin Concentrations [During months 6-12 after study agent adminstration]

   Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 data and mean ± SE for the difference between the pre-treatment and months 6-12 means for 3 subjects per group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Have a diagnosis of AAT-deficiency, as defined by a serum AAT level of less than 11 µM and a phenotype or genotype either homozygous for PIZ or compound heterozygous consisting of PIZ and another allele known to be associated with disease

2. Be at least 18 and not more than 75 years of age

3. Have a forced expiratory volume at one second (FEV1) >25% of predicted value (post bronchodilator)

4. Weigh ≤ 90 kg

5. Not receiving AAT augmentation therapy currently or with the past 3 months, and not planning to begin such therapy for at least 12 months after administration of rAAV1-CB-hAAT

6. Be willing to discontinue aspirin, aspirin-containing products, and other drugs that may alter platelet function, 7 days prior to dosing, resuming no earlier than 24 hours after the dose has been administered

7. Have acceptable laboratory parameters:

• Hemoglobin ≥ 11.2 g/dL for females, ≥ 12.8 g/dL for males,

• White blood cell count 3,300 - 12,000 cells/mm3,

• Platelet count 125,000 - 550,000/mm3,

• Serum creatine kinase (CK) ≤ 3 times upper normal range for study laboratory,

• Alanine aminotransferase (ALT) ≤ 2 times upper normal range for study laboratory,

• Serum bilirubin ≤ 1.5 times upper normal range for study laboratory,

• Serum creatinine within normal range for study laboratory,

• Prothrombin time (PT) ≤ 14.5 seconds and partial thromboplastin time (PTT)

≤ 36 seconds,

• Normal urine dipstick (negative glucose, negative hemoglobin, and negative or trace protein),

1. For females of childbearing potential:

• A negative pregnancy test (urine or serum) at screening and at baseline (within 2 days before administration of study agent)

• Agreement to consistently use barrier contraception (condoms, diaphragm or cervical cap with spermicide) or another form of contraception (e.g. intrauterine device or hormonal contraception) from the screening visit until 12 months after administration of rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy

1. For males of reproductive potential, agreement to consistently use barrier contraception (condoms with spermicide) for 12 months after administration of rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy,

2. Provide signed informed consent before screening

Exclusion Criteria:

1. Prior receipt of any AAV gene therapy product

2. Use of anticoagulants or anti-platelet agents within 7 days prior to study agent administration

3. History of immune response to human AAT augmentation therapy as indicated by clinical history of an adverse immune response to infusion and/or decreased therapeutic effect in combination with documentation of serum anti-AAT antibodies

4. Use of acute oral or intravenous antibiotic therapy for a respiratory infection within 28 days prior to study agent administration (long-term maintenance or chronic suppressive oral antibiotics, and antibiotics for a non-respiratory indication, are allowed)

5. Use of oral or systemic corticosteroids within 28 days prior to study agent administration

6. Use of any investigational agent, or any immunosuppressive drug(s), within 3 months prior to enrollment

7. For females of childbearing potential, a positive pregnancy test at screening or baseline (within 2 days before rAAV1-CB-hAAT administration) Note: At the Cincinnati Children's Hospital Medical Center site, women of childbearing potential were not permitted to enroll in the study.

8. Females who are breast feeding

9. Have a significant abnormal EKG finding at screening and/or cardiac disease (e.g. recent myocardial infarction or CHF) within past 6 months

10. Have had pulmonary edema or a pulmonary embolism within the past 6 months

11. Have a history of immunodeficiency or other medical condition which leads the investigator to believe that the participant cannot comply with the protocol requirements or that may place the participant at an unacceptable risk for participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Jewish Health	Denver	Colorado	United States	80206
2	University of Massachusetts Medical Center	Worcester	Massachusetts	United States	01655
3	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
4	Beaumont Hospital	Dublin		Ireland	2

Sponsors and Collaborators

• Applied Genetic Technologies Corp
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Terence R. Flotte, MD, University of Massachusetts Medical School, Worcester, MA
• Principal Investigator: Bruce C. Trapnell, MD, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
• Principal Investigator: Robert A. Sandhaus, MD, PhD, National Jewish Health, Denver, CO
• Principal Investigator: Noel G. McElvaney, MB, BCh, BAO, Beaumont Hospital, Dublin, Ireland

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Applied Genetic Technologies Corporation

Publications

• Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, Rouhani F, Conlon TJ, Calcedo R, Betts MR, Spencer C, Byrne BJ, Wilson JM, Flotte TR. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16363-8. doi: 10.1073/pnas.0904514106. Epub 2009 Aug 12. Erratum in: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17606.

• Responsible Party: Applied Genetic Technologies Corp
• ClinicalTrials.gov Identifier: NCT01054339
• Other Study ID Numbers: AGTC-AAT-002; 2009-014286-20; R01HL069877; R01FD003896
• First Posted: Jan 22, 2010
• Last Update Posted: Mar 28, 2019
• Last Verified: Jul 1, 2016

• Keywords provided by Applied Genetic Technologies Corp: Alpha-1 antitrypsin deficiency; Adeno-associated virus vector; AAV; Gene therapy; Human gene transfer
• Additional relevant MeSH terms: Alpha 1-Antitrypsin Deficiency

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from two clinical trial sites (University of Massachusetts Medical Center and Cincinnati Children's Hospital Medical Center).

Arm/Group Title	Low Dose	Middle Dose	High Dose
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site	rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites	rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
Period Title: Overall Study
STARTED	3	3	3
COMPLETED	3	3	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Low Dose	Middle Dose	High Dose	Total
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site	rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites	rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites	Total of all reporting groups
Overall Participants	3	3	3	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	3 100%	3 100%	8 88.9%
>=65 years	1 33.3%	0 0%	0 0%	1 11.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.3 (26.4)	48.7 (9.3)	54.3 (3.5)	51.1 (14.3)
Sex: Female, Male (Count of Participants)
Female	3 100%	2 66.7%	2 66.7%	7 77.8%
Male	0 0%	1 33.3%	1 33.3%	2 22.2%
Alpha-1 antitrypsin phenotype (participants) [Number]
ZZ	2 66.7%	3 100%	3 100%	8 88.9%
SZ	1 33.3%	0 0%	0 0%	1 11.1%
Serum total alpha-1 antitrypsin concentration (microMolar) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microMolar]	6.56 (2.00)	3.54 (0.12)	3.45 (0.25)	4.31 (1.88)

Outcome Measures

1. Primary Outcome

Title	Frequency of Grade 3 or 4 Adverse Events
Time Frame	During 1 year after study agent administration

Outcome Measure Data

Analysis Population Description

Analysis based on all subjects enrolled in study.

Arm/Group Title	Low Dose	Middle Dose	High Dose
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site	rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as a total of 32 IM injections distributed across three muscle sites	rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as100 IM injections distributed across 10 muscle sites
Measure Participants	3	3	3
Number [participants]	0 0%	0 0%	1 33.3%

2. Secondary Outcome

Title	Changes in Serum M-specific Alpha-1 Antitrypsin Concentration
Description	Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 values and mean ± SE for the difference between the pre-treatment and months 6-12 means for 2 subjects in the low dose group and 3 subjects in each of the other two groups. The monoclonal antibody used to determine serum M-specific AAT concentrations has very little cross-reactivity with Z type AAT but cross-reacts strongly with S type AAT, causing results for this assay to be spuriously high for subject 303 in the low dose group.
Time Frame	During months 6-12 after study agent adminsitration

Outcome Measure Data

Analysis Population Description

One subject in low dose group had AAT phenotype SZ, which made measurement of M-specific serum alpha-1 antitrypsin concentration invalid.

Arm/Group Title	Low Dose	Middle Dose	High Dose
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site	rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites	rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
Measure Participants	2	3	3
Mean (Standard Error) [nanomolar]	31.5 (7.56)	71.8 (22.73)	239.2 (27.57)

3. Secondary Outcome

Title	Changes in Serum Total Alpha-1 Antitrypsin Concentrations
Description	Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 data and mean ± SE for the difference between the pre-treatment and months 6-12 means for 3 subjects per group.
Time Frame	During months 6-12 after study agent adminstration

Outcome Measure Data

Analysis Population Description

Analysis based on all subjects enrolled in study.

Arm/Group Title	Low Dose	Middle Dose	High Dose
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site	rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites	rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
Measure Participants	3	3	3
Mean (Standard Error) [micromolar]	0.33 (1.14)	0.16 (0.10)	0.19 (0.16)

Adverse Events

Time Frame	1 year
Arm/Group Title	Low Dose		Middle Dose		High Dose
Arm/Group Description	rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site		rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites		rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
All Cause Mortality
	Low Dose		Middle Dose		High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Dose		Middle Dose		High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		1/3 (33.3%)
Gastrointestinal disorders
diverticulitis	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Other (Not Including Serious) Adverse Events
	Low Dose		Middle Dose		High Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Lymphadenopath	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Gastrointestinal disorders
Diverticulosis	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Hiatus hernia	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Nausea	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Gastroenteritis viral	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Gastrointestinal disorder	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
General disorders
Injection site discomfort	2/3 (66.7%)	2	2/3 (66.7%)	2	2/3 (66.7%)	2
Influenza-like illness	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Injection site atrophy	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Injection site erythema	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1
Injection site pain	0/3 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1
Malaise	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Post-procedural discomfort	2/3 (66.7%)	2	1/3 (33.3%)	1	1/3 (33.3%)	1
Injection site hemorrhage	1/3 (33.3%)	1	3/3 (100%)	3	3/3 (100%)	3
Pyrexia	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Infections and infestations
Ear infection	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0
Upper respiratory tract infection	0/3 (0%)	0	1/3 (33.3%)	1	2/3 (66.7%)	2
Bronchitis	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Gingival abscess	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Oral candidiasis	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Sinusitis	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Urinary tract infection	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Arthropod bite	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Post procedural edema	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Post procedural hematoma	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Procedural pain	3/3 (100%)	3	1/3 (33.3%)	1	1/3 (33.3%)	1
Investigations
Blood creatine phosphokinase increased	0/3 (0%)	0	1/3 (33.3%)	1	3/3 (100%)	3
Metabolism and nutrition disorders
Dehydration	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Muscle spasms	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0
Muscle strain	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Muscle twitching	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Back pain	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Bone lesion	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Limb discomfort	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Musculoskeletal stiffness	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Myalgias	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Neck pain	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Pain in extremity	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Nervous system disorders
Headache	0/3 (0%)	0	2/3 (66.7%)	2	0/3 (0%)	0
Anosmia	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Dizziness	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Psychiatric disorders
Anxiety	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chest pain	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Dyspnea exertional	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Infective exacerbation of chronic obstructive pulmonary diseases	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Lung neoplasm	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Sinus headache	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Throat irritation	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Furuncle	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Rash	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Rash erythematous	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0
Skin hemorrhage	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Urticaria	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Vascular disorders
Ecchymosis	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0
Phlebitis superficial	1/3 (33.3%)	1	1/3 (33.3%)	1	0/3 (0%)	0
Aortic Aneurysm	0/3 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0
Orthostatic hypotension	0/3 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1
Postmastectomy lymphedema syndrome	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0

Limitations/Caveats

Study results based on small number of subjects.

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.