Not available

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2015-005814-31-IT
• Date of registration: 14/01/2021
• Prospective Registration: No
• Primary sponsor: NEURODERM LTD.
• Public title: Not available
• Scientific 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 (BeyoND) - BeyoND
• Date of first enrolment: 23/06/2016
• Target sample size: 210
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005814-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: 2 dosages of IMP will be studied: Regimen 1 (720 LD/90 CD) vs Regimen 2 (537,6 LD/67,2 CD) If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Spain, United States

Contacts

• Name: Lilach Zaddik
• Affiliation: NeuroDerm Ltd.

• Name: Lilach Zaddik
• Affiliation: NeuroDerm Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for study entry subjects in Cohort 1 (previously completed
the treatment period in protocol ND0612H-006 within one month prior to
enrolling to ND0612H-012) must satisfy all of the following criteria:
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.
To be eligible for study entry subjects in Cohort 2 (ND0612 naïve
subjects and subjects who completed treatment in a ND0612 clinical
study more than one month before screening) must satisfy all of the
following criteria:
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 noncompliant
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 nonlactating
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
Subjects in Cohort 1 and Cohort 2 will be excluded from the study if one
or more of the following criteria listed below are applicable.
1.Previously unable to tolerate ND0612 and/or have experienced intolerable adverse drug reactions associated with its use,
regardless of the dosing regimen administered.
For Cohort 2 the following exclusion criteria apply:
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

advanced Parkinson's disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Soluzione di levodopa/carbidopa
Product Code: ND0612
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LEVODOPA
CAS Number: 59-92-7
Current Sponsor code: -
Other descriptive name: LEVODOPA (LD)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
INN or Proposed INN: CARBIDOPA
CAS Number: 38821-49-7
Current Sponsor code: -
Other descriptive name: CARBIDOPA (CD)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 7-

Primary Outcome(s)

Main Objective: The primary objective of the study is to assess the long term safety
(systemic and local) and tolerability of continuous SC infusion of
ND0612. Assessment will be based on adverse events of special interest (AESI), i.e.,
infusion site reactions,cases of hypersensitivity, polyneuropathy.
edema, pain, hematoma and nodules (local safety). Tolerability will be
assessed based on the percentage of subjects that complete the 12
month treatment period of the study and the percentage of subjects who
discontinue from the 12-month treatment period due to an AE.

Secondary Objective: Further Safety Objectives: (assessed based on 12 month data):
• To further assess the safety and tolerability of ND0612 including
suicidality (Columbia - Suicide Severity Rating Scale [C-SSRS]),
Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale
(QUIP RS), excessive daytime sleepiness (Epworth Sleepiness Scale
[ESS]), vital signs, laboratory tests, and electrocardiogram (ECG) data.
Further Safety Objective assessed based on data up to 36 months:
• To assess the long-term safety (systemic and local) and tolerability of
continuous SC infusion of ND0612. Assessment will be based on AEs,
with a focus on infusion site skin reactions and infusion site inspections
for erythema, edema, pain, hematoma and nodules (local safety).

Primary end point(s): The primary endpoint in this study is a safety endpoint assessing AEs,
with a focus on infusion site skin reactions of continuous SC infusion of
ND0612 throughout the study period. Local safety at the infusion sites
will be assessed as the proportion of subjects with clinically significant
skin reactions and severity of skin reactions according to the following
local safety parameters: erythema, edema, pain, hematoma and nodules.

Timepoint(s) of evaluation of this end point: Month 12 visit

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Month 12 visita

Secondary end point(s): The secondary safety endpoints to be assessed for the 12-month treatment period include:
• Assessment of suicidal behavior and ideation (C-SSRS responses, including the number of subjects experiencing at least 1 event of suicidal ideation, at least 1 event of suicidal behavior, at least 1 event of suicidal ideation or behavior and selfinjurious behavior without suicidal intent, changes from Baseline in C-SSRS categories (No Suicidal Ideation or Behavior, Suicidal Ideation and Suicidal Behavior) and changes from Baseline in C-SSRS suicidal ideation)
• Assessment of impulsive compulsive behavior (QUIP-RS total scores)
• Epworth Sleepiness Scale (ESS total score)
• Vital signs with a focus on orthostatic BP (possible dopaminergic side effect)
• Laboratory data (hematology and biochemistry), including dipstick urinalysis results evaluation
• 12-lead ECG parameters, including ECG interpretation of clinical significance
• Physical examination
• Prior and concomitant medications

The exploratory efficacy endpoints assessed for 12 months of treatment are:
• Change in daily "ON" time without troublesome dyskinesia (defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia) from Baseline to the 12-month visit based on home "ON/OFF" diaries.
* Change in daily "OFF" time from Baseline to the 12 month visit, based on "ON/OFF" home diaries
* Change in total daily dose of oral LD/DDI from Baseline to the 12 month visit
• Proportion of responders at the 12-month visit based on daily "OFF" time recorded in home "ON/OFF" diaries. A responder is defined as a subject that experiences =50% reduction in "OFF" time from Baseline.
• Change in daily "ON" time with troublesome dyskinesia in a subset of subjects who had more than 1 hour of troublesome dyskinesia at Baseline, based on home "ON/OFF" diaries from Baseline to the 12-month visit.
* Change in PDQ-39 scores from Baseline to the 12 month visit
* Change in EQ-5D-5L scores from Baseline to the 12 month visit
* Change in UPDRS Part II (ADL) from Baseline to the 12 month visit
* Change in CGI-Severity and CGI-Improvement from Baseline to the 12 month visit
* Change in SGI-Improvement from Baseline to the 12 month visit
* Change in PDSS total score from Baseline to the 12 month visit
* Change in UPDRS Part III (motor score) from Baseline to the 12 month visit
* Change from baseline to month 12 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).
* Change from baseline to month 12 in ND0612 total dose.
* Proportion of patients who reduced ND0612 total dose at any time during the study.

Secondary ID(s)

ND0612H-012

2015-005814-31-AT

Source(s) of Monetary Support

NEuroDerm Ltd.

Ethics review

Status: Approved
Approval date: 23/06/2016
Contact: