The primary objective of this trial will be to evaluate the effect of ONO-2506PO (1200 mg once daily) on the slope of respiratory function (slow vital capacity (SVC) expressed as a percentage of the predicted value) over 12 months compared with…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this trial will be to evaluate the effect of
ONO-2506PO (1200 mg once daily) on the slope of respiratory function (slow
vital capacity (SVC) expressed as a percentage of the predicted value) over 12
months compared with placebo group.
Secondary outcome
The secondary objectives of this trial will be to evaluate the effect of
ONO-2506PO (1200 mg once daily) on:
Respiratory Function
* The slope of respiratory function (SVC expressed as a percentage of the
predicted value) over 18 months
* Time to SVC reaching below 50% of the predicted value over 12 and 18 months
Survival
* Survival (defined as death) over 12 and 18 months
* Death, tracheotomy or permanent assisted ventilation over 12 and 18 months
Functional Status
* The slope of functional status using the ALS Functional Rating Scale
(ALSFRS-R) over 12 and 18 months
* Time to loss of function using ALSFRS-R over 12 and 18 months
Muscle Strength
* The slope of muscle strength using MRC muscle score over 12 and 18 months
Quality of Life
* Quality of life (QoL) using EuroQoL (EQ-5D) over 12 and 18 months
Safety and tolerability
* Vital signs, physical examination, weight, 12-Lead ECG, clinical laboratory
tests and adverse events monitoring
Background summary
Protocol page 14-21.
Study objective
The primary objective of this trial will be to evaluate the effect of
ONO-2506PO (1200 mg once daily) on the slope of respiratory function (slow
vital capacity (SVC) expressed as a percentage of the predicted value) over 12
months compared with placebo group.
8.2 SECONDARY OBJECTIVES
The secondary objectives of this trial will be to evaluate the effect of
ONO-2506PO (1200 mg once daily) on:
Respiratory Function
* The slope of respiratory function (SVC expressed as a percentage of the
predicted value) over 18 months
* Time to SVC reaching below 50% of the predicted value over 12 and 18 months
Survival
* Survival (defined as death) over 12 and 18 months
* Death, tracheotomy or permanent assisted ventilation over 12 and 18 months
Functional Status
* The slope of functional status using the ALS Functional Rating Scale
(ALSFRS-R) over 12 and 18 months
* Time to loss of function using ALSFRS-R over 12 and 18 months
Muscle Strength
* The slope of muscle strength using MRC muscle score over 12 and 18 months
Quality of Life
* Quality of life (QoL) using EuroQoL (EQ-5D) over 12 and 18 months
Safety and tolerability
* Vital signs, physical examination, weight, 12-Lead ECG, clinical laboratory
tests and adverse events monitoring
Study design
This is a double blind, placebo controlled, parallel group Phase II study, in
which ONO-2506PO (1200mg once daily) or placebo is administered once a day for
18 months to ALS patients who have had onset of muscle weakness within 14
months of randomisation, in the presence of stable standard Riluzole therapy.
Study burden and risks
The adverse events that have been experienced in the past with previous studies
have been discussed earlier. However as with all new drugs we cannot be
absolutely sure of the possible disadvantages or risks that may occur if you
take part.
Another aspect you need to be certain of is that you have not suffered from the
disease for more than 14 months. The reason is that in a previous study, some
more deaths were observed in the patient group receiving ONO-2506PO only if
they had disease duration of more than 14 months. Within 412 patients who had
duration of the disease longer than 14 months, 10 deaths were observed in the
placebo group, and 29 in the group receiving ONO-2506PO. One reason may be
that the patients in the ONO-2506PO group were more severely ill already at the
beginning of the study. Out of 111 patients with short disease duration of
less than 14 months, 17 died in the placebo treatment group and only 9 in the
group receiving ONO-2506PO.
This treatment might harm an unborn baby; therefore you should not take part in
this study if you are pregnant, breast-feeding or you intend to become pregnant
during the study.
If you are a woman who might become pregnant, you will be asked to have a
pregnancy test before taking part. You must agree to use a reliable form of
contraception during the study. Adequate methods of contraception include but
are not limited to barrier method (i.e. condoms, diaphragm with spermicide
gel) surgical sterilisation, vasectomy and abstinence.
If you do become pregnant during the course of the study, you must inform the
doctor immediately so appropriate action can be discussed and trial treatment
must be stopped. You will be withdrawn from the study but will continue to
attend clinic visits to monitor your health.
Please share this information with your partner if it is appropriate.
It is known that the study medication may affect sperm or semen and therefore
you must not father a child during this study or for a period of 90 days after
treatment. If your partner might become pregnant you must use reliable forms
of contraception during the trial and for 90 days following the study. If your
partner becomes pregnant during the study or in the 90 days following the study
you should inform the doctor immediately.
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United Kingdom
Listed location countries
Age
Inclusion criteria
1. Adult males and females aged 18 to 75 years.
2. Diagnosis of clinically possible, clinically probable laboratory-supported, clinically probable, or clinically definite ALS (according to WNF EL Escorial diagnostic criteria, revised according to the Airlie House Conference 1998)
3. Onset of muscle weakness within 14 months of randomisation
4. Baseline SVC greater than or equal to 70% of predicted normal at Visit 1 (screening visit)
5. Concomitant standard Riluzole therapy (50mg twice daily) for at least 2 weeks prior to Visit 1(screening visit), with liver function test (LFT) results within two times the upper limit of the normal range
6. Ability to swallow without the requirement for nasogastric or PEG feeding as evidenced by a score of * 3 on ALSFRS-R question # c (swallowing) at Visit 1 (screening visit)
7. Agreement for themselves or their partner to use an adequate method of contraception throughout the study and for 2 weeks after post study visit. Adequate methods of contraception for themselves or their partner include but are not limited to barrier method (i.e. condoms, diaphragm with spermicide gel), surgical sterilisation, vasectomy and abstinence.
8. Able and willing to give written informed consent, personally or via their legally authorised representative
Exclusion criteria
1. Presence of a tracheotomy, mechanical ventilation or non-invasive ventilation as evidenced by a score of * 3 on ALSFRS-R question # i (respiratory insufficiency) at Visit 1 (screening visit)
2. Requirement for prescription drugs used for potential neuroprotective benefit listed in section 10.5.3.1, for one month prior to Visit 1 (screening visit)
3. Requirement for prescription drugs that are metabolised via the cytochrome P450 2C9 listed in section 10.5.3.2, for one week prior to Visit 1 (screening visit).
4. A clinically relevant medical history or presence of respiratory diseases or disorders (such as moderate-to-severe asthma and chronic obstructive pulmonary disease) that, in the opinion of the Investigator, may pose an unwarranted risk to the subject or confound the results of the study.
5. A history or presence of malignancy within the past 3 years.
6. A history or presence of other life threatening diseases within the past 3 years.
7. A clinically relevant medical history or presence of cardiovascular, gastrointestinal, renal, hepatic, endocrine/metabolic, neurologic, lymphatic, haematologic, immunologic, musculoskeletal, connective tissue, dermatologic, genito/urinary, psychiatric diseases or disorders that, in the opinion of the investigator, may pose an unwarranted risk to the subject or confound the results of the study.
8. Presence or intention of pregnancy and breast feeding (female subjects only).
9. Males with the intention of fathering a child during the study period.
10. A history of drug or alcohol abuse (alcoholic subjects who are recovered for at least 2 years will be allowed to enrol in the study).
11. Subjects who have used any investigational drug and /or participated in any clinical trial within 3 months of entry to this study.
12. Subjects who have previously received ONO-2506PO
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002660-26-NL |
| CCMO | NL15677.041.06 |