A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease

Parkinson's Disease Clinical Trial

— BeyoND  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02726386
• Other study ID #: ND0612H-012
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 4, 2016
• Est. completion date: February 2027

Study information

• Verified date: January 2024
• Source: NeuroDerm Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 214
• Est. completion date: February 2027
• Est. primary completion date: September 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• ND0612
ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system

Locations

Country	Name	City	State
Austria	Medical University Innsbruck	Innsbruck
Czechia	NEUROHK, s.r.o.	Chocen
Czechia	Clintrial s.r.o.	Praha
Czechia	Vestra Clinics, s.r.o.	Rychnov nad Knežnou
France	Centre Hospitalier d'Aix	Aix-en-Provence
France	CHU d'Amiens, Hopital Sud	Amiens Cedex 1
France	Hopital Neurologique Pierre Wertheimer	BRON Cedex
France	Hôpital Gabriel Montpied	Clermont-Ferrand Cedex 1
France	Hopital Roger Salengro	Lille Cedex
France	Hopital de la Timone	Marseille
France	CHU de Poitiers	Poitiers
Germany	Kliniken Beelitz GmbH	Beelitz-Heilstätten
Germany	St. Josefs Hospital	Bochum
Germany	Klinikum-Bremerhaven Reinkenheide	Bremerhaven
Germany	Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet Dresden	Dresden
Germany	Klinik Haag	Haag in Oberbayern
Germany	Universitaets-und Rehabilitationskliniken Ulm	Ulm
Israel	Barzilai MC	Ashkelon
Israel	Hadassah Medical Center, Ein-Kerem Campus	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Sourasky Medical Center	Tel Aviv
Italy	University Foundation	Chieti
Italy	AOU Pisa	Pisa
Italy	IRCCS San Raffaele Pisana	Rome
Italy	IRCCS Hospital San Camillo Venice	Venice
Poland	Centrum Medyczne PLEJADY	Kraków
Poland	Krakowska Akademia Neurologii Sp. z o.o.	Kraków
Poland	Indywidualna Praktyka Lekarska prof. dr hab	Lublin
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario de la Princesa	Madrid
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Maryland, Neurology	Baltimore	Maryland
United States	Parkinson's Disease and Movement Disorder Center of Boca Raton	Boca Raton	Florida
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Unity Point Health	Des Moines	Iowa
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	The Parkinsons and Movement Disorder Institute	Fountain Valley	California
United States	Neuro Pain Medical Center	Fresno	California
United States	MD Clinical	Hallandale Beach	Florida
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	University of Florida Health at Jacksonville	Jacksonville	Florida
United States	Clinical Trials Inc.	Little Rock	Arkansas
United States	Neurology Associates, PA	Maitland	Florida
United States	Xenoscience	Phoenix	Arizona
United States	Parkinsons Disease Treatment Center of Southwest Florida	Port Charlotte	Florida
United States	Synergy Trials	Richmond	Virginia
United States	Suncoast Neuroscience Associates	Saint Petersburg	Florida
United States	Pyramid Clinical Research	Somerset	New Jersey
United States	Premier Research	Spokane	Washington
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	USF Health Parkinson's Disease and Movement Disorders	Tampa	Florida
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	Sentara Neuroscience Institute	Virginia Beach	Virginia
United States	Henry Ford Hospital	West Bloomfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
NeuroDerm Ltd.

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  France,  Germany,  Israel,  Italy,  Poland,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of Daily "ON" Time Without Troublesome Dyskinesia	Exploratory endpoint. "ON" time without troublesome dyskinesia is defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. Daily "ON" time without troublesome dyskinesia will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.	Baseline to Month 12
Other	Change of Daily "OFF" Time	Exploratory endpoint. Daily "OFF" time will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.	Baseline to Month 12
Other	Change of Total Daily Dose of Oral LD/DDI	Exploratory endpoint. Total daily dose of oral Levodopa (LD)/Dopa-Decarboxylase Inhibitor (DDI).	Baseline to Month 12
Other	Proportion of Responders	Exploratory endpoint. A responder is defined as a subject that experiences =50% reduction in "OFF" time from Baseline. Improvement of =50% in "OFF" time will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.	Baseline to Month 12
Other	Change of Daily "ON" Time With Troublesome Dyskinesia	Exploratory endpoint. Daily "ON" time with troublesome dyskinesia will be assessed based on home "ON/OFF" diaries in a subset of subjects who had more than 1 hour of troublesome dyskinesia at baseline. It will be normalized to 16 hours of awake time.	Baseline to Month 12
Other	Change of PDQ-39 Scores	Exploratory endpoint. Quality of Life in Parkinson's Disease (PDQ)-39 is a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. Higher scores indicate a worse quality of life.	Baseline to Month 12
Other	Change of EQ-5D-5L Scores	Exploratory endpoint. The perception of general quality of life (QoL) will be rated by the subjects using the EuroQoL 5-dimensions 5-severity levels (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of 2 pages, the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. Decrease in the 5-dimensions scores and increase in EQ VAS score will indicate improvement.	Baseline to Month 12
Other	Change of UPDRS Part II (ADL)	Exploratory endpoint. The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater impairments for daily activities.	Baseline to Month 12
Other	Change in CGI-Severity and CGI-Improvement	Exploratory endpoint. Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) are rated by the investigator or designee. CGI-S employs a 7-point scale with 1 being "not at all ill" and 7 being "among the most severely ill subjects" for severity rating. The CGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.	Baseline to Month 12
Other	Change in SGI-Improvement	Exploratory endpoint. Subjects Global Impression of Improvement (SGI-I) is rated by the subject. The SGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.	Baseline to Month 12
Other	Change in PDSS-2 Total Score	Exploratory endpoint. The quality of night sleep is rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality.	Baseline to Month 12
Other	Change in UPDRS Part III (Motor Score)	Exploratory endpoint. The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater motor impairment.	Baseline to Month 12
Other	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)	Exploratory endpoint. Good "ON" time (or "ON" time without troublesome dyskinesia) is defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. For this endpoint, Good "ON" time and "OFF" time will be assessed based on home "ON/OFF" diaries during the first 3 hours since the subject is awake after 06:00 (6 am).	Baseline to Month 12
Other	Change in ND0612 Total Dose	Exploratory endpoint. Change in ND0612 total daily dose.	Baseline to Month 12
Other	Proportion of Patients Who Reduced ND0612 Total Dose	Exploratory endpoint. Proportion of patients who reduced ND0612 total dose at any time during the study.	Baseline to Month 102
Primary	Adverse Events (Long-term Safety)	Long-term safety (systemic and local) assessment will be based on adverse events (AEs), with a focus on adverse events of special interest (AESI), i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.	Baseline to Month 12
Primary	Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability)	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.	Baseline to Month 12
Secondary	Adverse Events (Long-term Safety)	Long-term safety (systemic and local) and tolerability will be based on AEs, with a focus on AESI, i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.	Month 12 to Month 102