Safety and Efficacy of Apovir for treatment of patients with ALS (Amyotrophic lateral sclerosis)

• Register: EUCTR
• Last refreshed on: 12 September 2016
• Main ID: EUCTR2012-002099-15-SE
• Date of registration: 01/08/2014
• Prospective Registration: Yes
• Primary sponsor: Apodemus AB
• Public title: Safety and Efficacy of Apovir for treatment of patients with ALS (Amyotrophic lateral sclerosis)
• Scientific title: A randomised, double blind, placebo controlled trial to evaluate the safety and efficacy of Apovir for treatment of patients with Amyotrophic lateral sclerosis
• Date of first enrolment: 15/09/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002099-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: The randomisation will be stratified by presence/absence of treatment with Riluzole at baseline. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes 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

Sweden

Contacts

• Name: Clinical Trials Information
• Affiliation: Apodemus AB

• Name: Clinical Trials Information
• Affiliation: Apodemus AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female study subjects fulfilling the probable or higher criteria for ALS according to the revised El-Escorial criteria
2. First documented symptom of ALS = 24 months before screening
3. The sum of the 3 respiratory items on the ALSFRS-R, 10: dyspnoea, 11: orthopnoea and 12: respiratory insufficiency, must total at least 10 points
4. Ability to walk without other walking aids than a crutch
5. 18 – 80 years at the time of screening
6. FEV% =70%
7. Study subjects with or without pharmacological treatment, i.e. Riluzole for ALS (study subjects with ongoing pharmacological treatment for ALS shall have received unchanged treatment as regards drug(s) and dose(s) for at least 1 month)

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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Women in fertile age with a positive pregnancy blood test, or planning to become pregnant during the period of the trial. Fertile women include any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal. Postmenopausal is defined as amenorrhea = 12 consecutive months without another cause
2. Sexually active men and women without highly effective contraceptive treatment, e.g. sterilisation, condoms and diaphragms with spermicide; oral contraceptives (including Progesterone-only pills in high dose) in combination with a barrier method; hormonal contraceptives alone are not sufficient
3. Active hepatitis B, active hepatitis C, or HIV infection
4. Serious cardiac disease including unstable or uncontrolled cardiac disease during the last 6 months and/or a previous history or present clinical signs of deep venous thrombosis
5. Major surgical procedure within 4 weeks prior to start of treatment
6. Participation in any other clinical trial within 30 days of inclusion (randomisation) in the trial or patients with unresolved investigational treatment-related adverse events
7. Other chronic disease or previous organ transplantation judged by the Investigator to interfere with the assessment of treatment success and/or ability to fully participate in the trial
8. Impaired kidney function with an absolute GFR calculated from cystatin C <60 mL/min
9. Known blood disease or Anaemia Haemoglobin <120 g/L for women and <130 g/L for men
10. Known haemoglobinopathy (e.g. thalassemia and sickle cell anaemia)
11. Patients that require immunosuppressive treatments including azathioprine, cyclosporine, systemic steroid treatment (e.g. prednisolone at doses of =10 mg/day or hydrocortisone) or has received such treatment within the last 6 months prior to randomization
12. Patients that are treated with drugs that can interact significantly with APO-P001; ethinylestradiol and/or ribavirin; azathioprine, didanosine, zidovudine, mercaptopurine, stavudine
13. Lack of suitability for participation in the trial, for any reason, as judged by the Investigator
14. Patients with clinical or other signs of frontal temporal lobe dementia (FTLD) or known heredity for FTLD


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

Health Condition(s) or Problem(s) studied

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

Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 17.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Pleconaril
Product Code: APO-P001
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PLECONARIL
CAS Number: 153168-05-9
Current Sponsor code: APO-P001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Copegus
Product Name: Ribavirin
Pharmaceutical Form: Capsule, hard
CAS Number: 36791-04-5
Other descriptive name: RIBAVIRIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Primary Safety Endpoint
Evaluations will be analysed throughout the whole CT.

Primary efficacy Endpoints
12 months

Primary end point(s): Primary Safety Endpoint
• Frequency and intensity of adverse events

Primary efficacy Endpoints
• Change in ALSFRS-R from baseline to 12 months using mean change of slope

Secondary Objective: SECONDARY EFFICACY OBJECTIVES
To investigate the effect of Apovir on disease progression of ALS assessed by ALSFRS-R score at the 4-weeks, 3-, 6-, 9-months, and Follow-up visits, and forced vital capacity (FVC), vital capacity (VC) and maximal voluntary ventilation (MVV) at the 4-weeks, 3-, 6-, 9-, 12-months, and Follow-up visits

To investigate the combined effect of Apovir on ALSFRS-R, and death or the use of definitive life supporting breathing assistance and death as assessed by Combined assessment of function and survival (CAFS) at the 4-weeks, 3-, 6-, 9-, 12-months, and follow-up visits

To investigate the effect of Apovir on time from onset of ALS symptoms to the use of definitive life supporting breathing assistance, or Death

To investigate the plasma concentrations of Apovir in patients with ALS

Refer to the protocol for further secondary objectives.

Main Objective: SAFETY OBJECTIVE
To investigate the safety and tolerability of the combination therapy of Apovir in patients with ALS

PRIMARY EFFICACY OBJECTIVE
To investigate the effect of Apovir on 12-months disease progression of ALS as assessed by ALSFRS-R score from baseline compared to placebo

Secondary Outcome(s)

Secondary end point(s): Change in disease progression of ALS as assessed by:
• Change in ALSFRS-R score from baseline to the 4-weeks, 3-, 6-, 9-, 12-months, and Follow-up visits
• Change in FVC, VC and MVV from baseline to the 4-weeks, 3-, 6-, 9-, 12-months, and Follow-up visits
• Change in CAFS from baseline to the 4-weeks, 3-, 6-, 9-, 12-months, and Follow-up visits
• Time from study inclusion and time of ALS symptoms onset to the use of definitive life supporting breathing assistance, or Death

Plasma concentrations of Apovir:
• Plasma concentrations Cpre dose of Apovir at the 4-weeks, 3-, 6-, and 12-months visits. Concentrations at 3 months will be compared to published data [Rhodes and Liu 2001 ; Khakoo et al 1998 ].

Timepoint(s) of evaluation of this end point: Refer to section 5.2

Secondary ID(s)

APOCT-001

Source(s) of Monetary Support

Apodemus AB