A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson’s Disease (BeyoND)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neuroderm Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Oct 2016 → ongoing

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513548-27-00

EudraCT number

2015-005814-31

ClinicalTrials.gov

NCT02726386

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

The primary objective of the study is to assess the long term safety (systemic and local) and tolerability of continuous SC infusion of ND0612.

Secondary objectives 1

1. 1. To further assess the safety and tolerability of ND0612 including suicidality, excessive daytime sleepiness, vital signs, laboratory tests and electrocardiogram data. 2. To assess the long-term safety (systemic and local) and tolerability of continuous SC infusion of ND0612.

Conditions and MedDRA coding

Parkinson's disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

Privacy reasons and Data Protection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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. Cohort 2: 5.Subjects must be stable on their anti-PD medications for at least 30 days before Day 1.
3. Cohort 2: 7.Must have a minimum of 2 hrs of “OFF” time per day with predictable early morning “OFF” periods as estimated by the subject.
4. Cohort 2: 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.
5. Cohort 2: 9.Mini Mental State Examination (MMSE) score ≥ 26.
6. Cohort 2: 10.No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or noncompliant in the study.
7. Cohort 2: 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.
8. Cohort 2: 12.Willing and able to administer the SC infusion alone or with the assistance of a study partner after a screening period up to 40 days and willing and able to comply with study requirements.
9. Cohort 2: 13. Subjects should have a named study partner.
10. Cohort 2: 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.
11. Cohort 1: 2.Subject has completed the treatment period of study ND0612H-006 not more than one month prior to enrolling in ND0612H-012.
12. Cohort 1: 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.
13. 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.
14. Cohort 2: 2.PD diagnosis consistent with the UK Brain Bank Criteria.
15. Cohort 2: 3.Modified Hoehn & Yahr scale in “ON” state of stage ≤3.
16. Cohort 2: 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.

Exclusion criteria 11

1. 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.
2. For Cohort 2 the following exclusion criteria apply: 1.Atypical or secondary parkinsonism.
3. Cohort 2: 2.Acute psychosis or hallucinations in past 6 months.
4. Cohort 2: 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.
5. Cohort 2: 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 treatment.
6. Cohort 2: 5. Positive serum serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) at the screening visit.
7. Cohort 2: 6. Prior neurosurgical procedure for PD, or Duodopa treatment
8. Cohort 2: 7. Subjects with a history of drug abuse or alcoholism within the past 12 months.
9. Cohort 2: 8. Clinically significant ECG rhythm abnormalities.
10. Cohort 2: 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.
11. Cohort 2: 10. Current participation in a clinical trial with an investigational product or past participation within the last 30 days before Day 1.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety endpoint assessing the long-term safety (systemic and local) and tolerability of continuous SC infusion of ND0612 throughout the 12-month treatment period.

Secondary endpoints 23

1. Assessment of suicidal behavior and ideation.
2. Assessment of impulsive compulsive behavior
3. Epworth Sleepiness Scale
4. Vital signs with a focus on orthostatic BP
5. Laboratory data (hematology and biochemistry), including dipstick urinalysis results evaluation
6. 12-lead ECG parameters, including ECG interpretation of clinical significance
7. Physical examination
8. Prior and concomitant medications
9. Change in daily “ON” time without troublesome dyskinesia
10. Change in daily “OFF” time from Baseline to the 12-month visit, based on home “ON/OFF” diaries
11. Change in total daily dose of oral LD/DDI from baseline to the 12 month visit
12. Proportion of responders at the 12-month visit based on daily “OFF” time recorded in home “ON/OFF” diaries.
13. 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.
14. Change in PDQ-39 scores from Baseline to the 12 month visit
15. Change in EQ-5D-5L scores from Baseline to the 12 month visit
16. Change in UPDRS Part II (ADL) from Baseline to the 12 month visit
17. Change in CGI-Severity and CGI-Improvement from Baseline to the 12 month visit
18. Change in SGI-Improvement from Baseline to the 12 month visit
19. Change in PDSS total score from Baseline to the 12 month visit
20. Change in UPDRS Part III (motor score) from Baseline to the 12 month visit
21. 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)
22. Change from baseline to month 12 in ND0612 total dose
23. Proportion of patients who reduced ND0612 total dose at any time during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neuroderm Ltd.

Sponsor organisation

Neuroderm Ltd.

Address

Bell Entrance, Floor 4, 3 Pekeris Street Floor 4 3 Pekeris Street

City

Rehovot

Postcode

7670212

Country

Israel

Scientific contact point

Organisation

Neuroderm Ltd.

Contact name

Scientific contact

Public contact point

Organisation

Neuroderm Ltd.

Contact name

Scientific contact

Third parties 9

Locations

4 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications