Clinical trial NCT02726386: A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease
Official title: A Multicenter, International, Open-label, Safety Study of ND0612, a Solution of Levodopa/Carbidopa Delivered Via a Pump System as a Continuous Subcutaneous Infusion in Subjects With Advanced Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Parkinson's Disease
Lead sponsor: NeuroDerm Ltd.
Sponsor class: INDUSTRY
First posted: 2016-04-01
Enrollment: 214
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, international, open-label, safety study of ND0612, a solution of levodopa/carbidopa (LD/CD) delivered via a pump system as a continuous SC infusion in subjects with advanced Parkinson's Disease (PD).

Detailed description: This is a multi-center, international, open-label, safety study of ND0612, a solution of LD/CD delivered via a pump system as a continuous SC infusion in subjects with advanced PD. Two cohorts of subjects are candidates for this study: subjects who completed treatment in study ND0612H-006 within one month prior to enrollment (Cohort 1) and ND0612 naïve subjects or subjects who completed treatment in a ND0612 clinical study more than one month before screening (Cohort 2). After screening procedures and confirmation of the inclusion/exclusion criteria, subjects and their study partners will be trained and assisted at their homes during the first week of treatment on the proper operation of the pump system. One mandatory home visit will be performed during the first week and then on a monthly basis during 12-months of treatment. Subjects will return for in-clinic visits at Week 1 and at Months 1, 2, 3, 4, 6, 9, and 12 for assessment of safety and efficacy variables. Subjects will be allowed to continue with study treatment for an optional treatment extension period of up to Month 102 and the clinic visits will be performed every 3 months to assess subject long-term safety. Safety follow-up visits will occur 1, 2, and 3 months after the last SC infusion of ND0612 or after early termination.

Eligibility criteria: INCLUSION CRITERIA:

Cohort 1.

1. Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).
2. Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012.
3. Willing and able to administer the SC infusion alone or with the assistance of a study partner and able to comply with the study specific procedures.

Cohort 2.

1. Male and female PD subjects of any race aged at least 30 years who sign an IRB/EC-approved ICF.
2. PD diagnosis consistent with the UK Brain Bank Criteria.
3. Modified Hoehn \& Yahr scale in "ON" state of stage ≤3.
4. Taking at least 4 doses/day of LD/DDI (or at least 3 doses/day of Rytary) and taking, or have attempted to take, at least one other PD treatment for at least 30 days.
5. Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
6. Subjects may have had prior exposure to SC apomorphine injections/infusion but must have stopped continuous apomorphine administration at least 4 weeks before the screening visit. Treatment with apomorphine is prohibited during the entire ND0612 treatment period.
7. Must have a minimum of 2 hrs of "OFF" time per day with predictable early morning "OFF" periods as estimated by the subject.
8. Must have predictable and well defined early morning "OFF" periods with a good response to LD for treatment of the early morning "OFF" in the judgement of the investigator.
9. Mini Mental State Examination (MMSE) score ≥26.
10. No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.
11. Female subjects must be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), postmenopausal (defined as cessation of menses for at least 1 year), or willing to practice a highly effective method of contraception. All female participants must be non-lactating and non-pregnant and have a negative urine pregnancy test at Screening and at Baseline. Female subjects of childbearing potential must practice a highly effective method of contraception (e.g., oral contraceptives, intrauterine devices, partner with vasectomy), 1 month before enrollment, for the duration of the study, and 3 months after the last dose of study drug. Alternatively, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle. If a subject is usually not sexually active but becomes active, the subject and sexual partner must comply with the contraceptive requirements detailed above.
12. Willing and able to administer the SC infusion alone or with the assistance of a study partner after a screening period of up to 40 days and willing and able to comply with study requirements.
13. Subjects should have a named study partner.

EXCLUSION CRITERIA:

Cohort 1 and 2. Previously unable to tolerate ND0612 and/or have experienced intolerable adverse drug reactions associated with its use, regardless of the dosing regimen administered.

Cohort 2.

1. Atypical or secondary parkinsonism.
2. Acute psychosis or hallucinations in past 6 months.
3. Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the Investigator makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
4. Any malignancy in the 5 years prior to randomization (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated).
5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the Screening visit.
6. Prior neurosurgical procedure for PD, or Duodopa treatment
7. Subjects with a history of drug abuse or alcoholism within the past 12 months.
8. Clinically significant ECG rhythm abnormalities.
9. Renal or liver dysfunction that may alter drug metabolism including: serum creatinine \>1.3 mg/dL, serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 x upper limit of normal (ULN), total serum bilirubin \>2.5 mg/dL.
10. Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.

Primary outcomes:
measure: Adverse Events (Long-term Safety)
timeFrame: Baseline to Month 12
measure: Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability)
timeFrame: Baseline to Month 12
Secondary outcomes:
measure: Adverse Events (Long-term Safety)
timeFrame: Month 12 to Month 102
Other outcomes:
measure: Change of Daily "ON" Time Without Troublesome Dyskinesia
timeFrame: Baseline to Month 12
measure: Change of Daily "OFF" Time
timeFrame: Baseline to Month 12
measure: Change of Total Daily Dose of Oral LD/DDI
timeFrame: Baseline to Month 12
measure: Proportion of Responders
timeFrame: Baseline to Month 12
measure: Change of Daily "ON" Time With Troublesome Dyskinesia
timeFrame: Baseline to Month 12
measure: Change of PDQ-39 Scores
timeFrame: Baseline to Month 12
measure: Change of EQ-5D-5L Scores
timeFrame: Baseline to Month 12
measure: Change of UPDRS Part II (ADL)
timeFrame: Baseline to Month 12
measure: Change in CGI-Severity and CGI-Improvement
timeFrame: Baseline to Month 12
measure: Change in SGI-Improvement
timeFrame: Baseline to Month 12
measure: Change in PDSS-2 Total Score
timeFrame: Baseline to Month 12
measure: Change in UPDRS Part III (Motor Score)
timeFrame: Baseline to Month 12
measure: Change in Percentage of "OFF" Time and Percentage of Good "ON" During the First 3 Hours Since the Subject is Awake After 06:00 (6 am)
timeFrame: Baseline to Month 12
measure: Change in ND0612 Total Dose
timeFrame: Baseline to Month 12
measure: Proportion of Patients Who Reduced ND0612 Total Dose
timeFrame: Baseline to Month 102
Locations:
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Little Rock
country: United States
facility: Clinical Trials Inc.
state: Arkansas
city: Fountain Valley
country: United States
facility: The Parkinsons and Movement Disorder Institute
state: California
city: Fresno
country: United States
facility: Neuro Pain Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorder Center of Boca Raton
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health at Jacksonville
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, PA
state: Florida
city: Port Charlotte
country: United States
facility: Parkinsons Disease Treatment Center of Southwest Florida
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates
state: Florida
city: Sunrise
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: USF Health Parkinson's Disease and Movement Disorders
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Des Moines
country: United States
facility: Unity Point Health
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland, Neurology
state: Maryland
city: Farmington Hills
country: United States
facility: QUEST Research Institute
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Somerset
country: United States
facility: Pyramid Clinical Research
state: New Jersey
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Richmond
country: United States
facility: Synergy Trials
state: Virginia
city: Virginia Beach
country: United States
facility: Sentara Neuroscience Institute
state: Virginia
city: Spokane
country: United States
facility: Premier Research
state: Washington
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Chocen
country: Czechia
facility: NEUROHK, s.r.o.
city: Praha
country: Czechia
facility: Clintrial s.r.o.
city: Rychnov nad Kněžnou
country: Czechia
facility: Vestra Clinics, s.r.o.
city: Aix-en-Provence
country: France
facility: Centre Hospitalier d'Aix
city: Amiens Cedex 1
country: France
facility: CHU d'Amiens, Hopital Sud
city: BRON Cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
city: Clermont-Ferrand Cedex 1
country: France
facility: Hôpital Gabriel Montpied
city: Lille Cedex
country: France
facility: Hopital Roger Salengro
city: Marseille
country: France
facility: Hopital de la Timone
city: Poitiers
country: France
facility: CHU de Poitiers
city: Beelitz-Heilstätten
country: Germany
facility: Kliniken Beelitz GmbH
city: Bochum
country: Germany
facility: St. Josefs Hospital
city: Bremerhaven
country: Germany
facility: Klinikum-Bremerhaven Reinkenheide
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden
city: Haag in Oberbayern
country: Germany
facility: Klinik Haag
city: Ulm
country: Germany
facility: Universitaets-und Rehabilitationskliniken Ulm
city: Ashkelon
country: Israel
facility: Barzilai MC
city: Jerusalem
country: Israel
facility: Hadassah Medical Center, Ein-Kerem Campus
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Chieti
country: Italy
facility: University Foundation
city: Pisa
country: Italy
facility: AOU Pisa
city: Rome
country: Italy
facility: IRCCS San Raffaele Pisana
city: Venice
country: Italy
facility: IRCCS Hospital San Camillo Venice
city: Kraków
country: Poland
facility: Centrum Medyczne PLEJADY
city: Kraków
country: Poland
facility: Krakowska Akademia Neurologii Sp. z o.o.
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska prof. dr hab
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
Study officials:
affiliation: NeuroDerm Ltd.
name: Laurence Salin, MD
role: STUDY_DIRECTOR
References:
citation: Poewe W, Stocchi F, Arkadir D, Ebersbach G, Ellenbogen AL, Giladi N, Isaacson SH, Kieburtz K, LeWitt P, Olanow CW, Simuni T, Thomas A, Zlotogorski A, Adar L, Case R, Oren S, Fuchs Orenbach S, Rosenfeld O, Sasson N, Yardeni T, Espay AJ; BeyoND study group. Subcutaneous Levodopa Infusion for Parkinson's Disease: 1-Year Data from the Open-Label BeyoND Study. Mov Disord. 2021 Nov;36(11):2687-2692. doi: 10.1002/mds.28758. Epub 2021 Sep 8.