Idiopathic Parkinson's Disease
Conditions
Brief summary
The purpose of this double blind study is to determine whether CERE-120 (adeno-associated virus serotype 2 \[AAV2\]-neurturin \[NTN\]) is effective and safe in the treatment of patients with idiopathic Parkinson's Disease. CERE-120 is administered via bilateral stereotactic injections targeting the putaminal region of the brain. The design of this study involves approximately 34 patients receiving CERE-120 treatment via stereotactic surgery and approximately 17 patients receiving sham stereotactic surgery (no CERE-120 administered).
Interventions
DRUGCERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN])
CERE-120 5.4 x 10\^11 vg
PROCEDURESham Surgery
Bilateral partial thickness burr holes placed, no intraparenchymal injections
Sponsors
Ceregene
Sangamo Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of bilateral, idiopathic Parkinson's Disease (PD) based on UK Brain Bank criteria with motor complications despite adequate oral antiparkinsonian therapy. * At least 5 years disease duration, relative to the anticipated date of surgery, since diagnosis of PD. * Males or nonpregnant females 35-75 years of age, inclusive. * A UPDRS motor scale score of 30 or greater in the practically defined off condition during the 30-day eligibility evaluation period. * Stable doses of antiparkinsonian medications and parkinsonian features for the 60-day period preceding the surgical procedure. * No conditions that would render the subject unsuitable for surgery, or that would interfere with any of the assessments of efficacy or safety in this trial. * Subject's informed consent prior to the performance of any study-specific procedures.
Exclusion criteria
* Subjects with atypical or secondary parkinsonism. * Any subject, in the judgment of the investigator, for whom participation in the study would pose a safety risk including, but not limited to, a history of any clinically significant medical, psychiatric, or laboratory abnormality. * History of treatment of PD by any procedure involving intracranial surgery or implantation of a device. * MRI of the brain within 12 months before the surgical procedure that indicates the presence of an abnormality that may interfere with the assessments of safety or efficacy or would, in the judgment of the investigator, represent a surgical risk to the subject. * Any disorder that precludes a surgical procedure (e.g., signs of sepsis or inadequately treated infection) or alters wound healing. * Receipt of antiplatelet agents for at least 10 days prior to the surgical procedure. * A score of less than or equal to 27 on the Folstein Mini-Mental examination performed during the eligibility evaluation period or clinical evidence of cognitive impairment that would affect the subject's ability to sign the informed consent or perform any of the protocol required assessments. * Chemotherapy, cytotoxic therapy, or immunotherapy within 6 weeks prior to the surgical procedure. * Vaccinations within 30 days prior to the surgical procedure. * History, within 2 years before the surgical procedure, of drug or alcohol abuse. * Treatment with neuroleptics within 1 year before the surgical procedure. * Any medical disability (e.g., severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of efficacy and safety in this trial or would compromise the ability of the subject to undergo study procedures (e.g., MRI, PET), or give informed consent. * History of prior gene transfer therapy. * Treatment with an investigational agent within 60 days before the surgical procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| UPDRS Part III OFF | Change from Baseline to 12 Month Visit | The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined off condition, 12 hours or more after the last administration of medication. |
Other
| Measure | Time frame | Description |
|---|---|---|
| UPDRS Part III OFF | Change from Baseline to 18 Month Visit | The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined off condition, 12 hours or more after the last administration of medication. |
Countries
United States
Participant flow
Recruitment details
58 subjects were recruited over a 10.5 month period at 11 centers in the US
Participants by arm
| Arm | Count |
|---|---|
| CERE-120 Treatment Group Subjects who were randomized to receive bilateral intraputaminal administration of CERE-120 (5.4 x 10\^11 vg) | 38 |
| Sham Surgery Control Group Subjects who were randomized to undergo sham surgery (partial burr holes) | 20 |
| Total | 58 |
Baseline characteristics
| Characteristic | CERE-120 Treatment Group | Sham Surgery Control Group | Total |
|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 7.56 | 57.3 years STANDARD_DEVIATION 8.3 | 59.1 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 38 participants | 20 participants | 58 participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 28 Participants | 15 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 38 | 20 / 20 |
| serious Total, serious adverse events | 13 / 38 | 4 / 20 |
Outcome results
Primary
UPDRS Part III OFF
The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined off condition, 12 hours or more after the last administration of medication.
Time frame: Change from Baseline to 12 Month Visit
Population: Subjects who completed the end-of-study visit at month 12 and had no important protocol deviations that potentially could have affected the efficacy assessment of the study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CERE-120 Treatment Group | UPDRS Part III OFF | -7.21 units on a scale |
| Sham Surgery Control Group | UPDRS Part III OFF | -6.91 units on a scale |
Other Pre-specified
UPDRS Part III OFF
The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined off condition, 12 hours or more after the last administration of medication.
Time frame: Change from Baseline to 18 Month Visit
Population: Subjects who completed the 12-month double-blind posttreatment period of the study continued to undergo double-blind assessments every 3 months until the last subject had completed the end-of-study visit at month 12. The LOCF method was used to impute data at month 18 for the subjects who had blinded data through month 15.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CERE-120 Treatment Group | UPDRS Part III OFF | -11.96 units on a scale | Standard Error 7.068 |
| Sham Surgery Control Group | UPDRS Part III OFF | -4.34 units on a scale | Standard Error 2.479 |