Assessing the effect of Triumeq in amyotrophic lateral sclerosis
Trial ID: ISRCTN88446415
Other - Phase 3 - No longer available
Background and study aims
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease. Unfortunately, there are limited medications available for ALS. The only available treatment is riluzole, which tends to provide only minimal benefit. Therefore, there is a high need for further research using other medications, to help improve the options for treatment for this disease.
There has been laboratory research that suggests that a virus called an endogenous retrovirus may be the cause or trigger for ALS in some people. This virus may be of the same family (although quite different) to the virus that causes HIV (also called ‘AIDS’). Researchers are intending to test if an anti-viral medication that is a very effective treatment for HIV, may also be effective for people who have ALS.
Triumeq, commonly prescribed for HIV treatment, is an antiviral medication that is a combination of three medications: dolutegravir 50 mg, abacavir 600 mg, and lamivudine 300 mg. Triumeq is approved by the Therapeutic Goods Administration (TGA) to treat HIV patients. However, it is not approved to treat ALS. Therefore, it is an experimental treatment for ALS.
The aim of this study is to determine whether Triumeq is effective at delaying the progression of ALS, and whether it is safe and well-tolerated in patients with ALS. The Lighthouse study demonstrated Triumeq to be safe and well tolerated in people with ALS.
Who can participate?
Patients aged 18 years and over with ALS
What does the study involve?
The entire study will last for around 2 years. Participation is voluntary. Participation in this study will involve up to 10 visits (about 2 hours each) roughly every 3 months, and as many telephone calls as participants would like, to make sure they are comfortable with the research process. Participants will be assessed throughout the project using assessment scales to determine if it is suitable for them to continue the medication.
Participants will be randomly allocated to receive either Triumeq or a matching placebo (dummy drug) once daily in addition to standard care. The random allocation will be done using a computer maintained by the King’s Clinical Trials Unit. Two thirds of research participants will receive active Triumeq and one third will receive matched placebo capsules. A placebo is a medication with no active ingredients and so has no medical benefit. It looks like the real thing, but it is not. The study is a ‘double-blind’ study. This means that neither participants nor the study doctor will know which treatment they are receiving. However, in certain circumstances the study doctor can find out which treatment participants are receiving. This study has been designed to make sure the researchers interpret the results fairly without any bias and avoids study doctors or participants jumping to conclusions.
There are a number of procedures and reviews that will be carried out at different times over the 24 months:
1. Demographics
2. Review of medical history
3. Physical examination/vital signs
4. Neurological exam
5. Blood collection
6. Urine collection
7. Throat or nasal swab: the doctor/nurse/research coordinator will perform either a throat or nasal swab to check for COVID-19 infection
8. Spirometry (breathing) test
9. Questionnaire completion
10. ECG test
What are the possible benefits and risks of participating?
The researchers cannot guarantee or promise that participants will receive any benefits from this research; however, possible benefits may include some relief of ALS symptoms. The tests provided may help participants learn about their general health. This study may assist doctors and scientists to help people suffering from symptoms with ALS in the future.
Medical treatments often cause side effects. Participants may have none, some or all of the effects listed below, and they may be mild, moderate or severe. There may be side effects that the researchers do not expect or do not know about and that may be serious. Many side effects go away shortly after treatment ends. However, sometimes side effects can be serious, long-lasting or permanent. If a severe side effect or reaction occurs, the study doctor may need to stop the treatment.
The following side effects have been experienced by people taking Triumeq:
Common side effects (occur in 1 out of 10 people): fever, not feeling well, discouragement, nausea, rash, irritability, loss of interest and/or pleasure, trouble concentrating and/or sleeping.
Uncommon side effects (occur in 1 out of 100 people): neuropathy (tingling in fingers and toes), anxiety, difficulty moving, weight loss, itching and hair loss as well as high blood sugar.
Rare side effects (occur in 1 out of 10, 0000 people): abnormal liver function tests, low blood pressure dizziness or light-headedness, fainting or lack of concentration or fatigue, acute inflammation of the pancreas, nausea, fever and a swollen and or tender abdomen and hepatitis, joint pain, abdominal pain and yellowing of the skin.
Where is the study run from?
King’s College London (UK)
When is the study starting and how long is it expected to run for?
January 2020 to June 2025
Who is funding the study?
1. National Institute for Health Research (NIHR) (UK)
2. FightMND (Australia)
3. Motor Neurone Disease Research Institute of Australia (Australia)
4. Treatment Research Initiative to Cure ALS (TRICALS)
Who is the main contact?
Elliott Phillips
elliott.phillips@kcl.ac.uk
Shared inbox
lighthouseii@kcl.ac.uk
Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Nervous System Diseases
- Motor neuron disease
Interventions
- Abacavir, lamivudine, dolutegravir
Eligibility
Inclusion criteria
- Current inclusion criteria as of 13/02/2024:
1. Age ≥18 years at the time of screening
2. Diagnosis of ALS according to the Gold Coast Criteria
3. Capable of providing informed consent and complying with trial procedures
4. TRICALS risk profile > -6.0 and < -2.0
5. Those taking Riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have stopped taking Riluzole at least 30 days prior to the baseline visit
6. Women must not become pregnant (e.g., post-menopausal, surgically sterile, using highly effective birth control methods or not having potentially reproductive sex) for the duration of the study plus five days. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. combined (oestrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception
7. Women of childbearing potential must have a negative serum pregnancy test at screening and be non-lactating. Patients will be advised regarding appropriate contraception. A menstruation history will be taken at each visit. Women of childbearing potential are defined as females who are fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy
8. For participants taking antacids (regularly or as required), the participant is willing and able to avoid taking antacids for at least 6 hours before and 2 hours after Triumeq
9. Participants taking taurursodiol supplements (TUDCA) can participate in this trial if the supplement does not contain sodium phenylbutyrate.
10. Participants taking taurursodiol supplements (TUDCA) that also contain sodium phenylbutyrate must be willing to stop supplementation 30 days prior to randomisation.
Previous inclusion criteria:
1. Age ≥ 18 years at the time of screening
2. Diagnosis of ALS according to the Gold Coast Criteria
3. Capable of providing informed consent and complying with trial procedures
4. TRICALS risk profile > -6.0 and < -2.0
5. Those taking Riluzole must be on a stable dose for at least 30 days prior to the baseline visit or must have stopped taking Riluzole at least 30 days prior to the baseline visit
6. Women must not become pregnant (e.g., post-menopausal, surgically sterile, using highly effective birth control methods or not having potentially reproductive sex) for the duration of the study. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. combined (oestrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception
7. Women of childbearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating. Women of childbearing potential are defined as females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period)
8. For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 2 hours before and 6 hours after Triumeq
Exclusion criteria
- Current exclusion criteria as of 13/02/2024:
1. People who are HLA-B*5701 positive
2. Known hypersensitivity to dolutegravir, abacavir or lamivudine, or to any of the excipients
3. Safety Laboratory Criteria at screening:
3.1. ALT ≥ 5 times upper limit of normal (ULN)
3.2. AST ≥ 3 times ULN
3.3. Bilirubin ≥ 1.5 times ULN with clinical indicators of liver disease
3.4. Creatinine clearance < 30 ml/min
3.5. Platelet concentration of < 100 x109 per l
3.6. Absolute neutrophil count of < 1x109 per l
3.7. Haemoglobin < 100 g/l
3.8. Amylase ≥ 2 times ULN
3.9. Lactate ≥ 2 times ULN
4. Moderate to severe hepatic impairment, as defined by local clinical guidelines
5. Presence of HIV antibodies at screening
6. Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C
7. Presence of Hepatitis B core or surface antigen at screening
8. Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening
9. Use of NIV ≥22 h per day or having a tracheostomy
10. Edaravone dose within 30 days prior to screening. Edaravone is approved by the FDA and in Japan, but remains an investigational product in Europe and Australia
11. Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness
12. Taking medication contraindicated with Triumeq: dofetilide or fampridine (dalfampridine)
13. Taking Tofersen within 3 months prior to screening.
Previous exclusion criteria:
1. People who are HLA-B*5701 positive
2. Known hypersensitivity to dolutegravir, abacavir or lamivudine, or to any of the excipients
3. Safety Laboratory Criteria at screening:
3.1. ALT ≥ 5 times upper limit of normal (ULN)
3.2. AST ≥ 3 times ULN
3.3. Bilirubin ≥ 1.5 times ULN
3.4. Creatinine clearance < 30 ml/min
3.5. Platelet concentration of < 100 x109 per l
3.6. Absolute neutrophil count of < 1x109 per l
3.7. Haemoglobin < 100 g/l
3.8. Amylase & lipase ≥ 2 times ULN
3.9. Lactate ≥ 2 times ULN
4. Moderate to severe hepatic impairment, as defined by local clinical guidelines
5. Presence of HIV antibodies at screening
6. Presence of Hepatitis C antibodies at screening unless participants have had effective treatment for Hepatitis C
7. Presence of Hepatitis B core or surface antigen at screening
8. Participation in any other investigational drug trial or using investigational drug within 30 days prior to screening
9. Use of NIV ≥22 h per day or having a tracheostomy
10. Edaravone dose within 30 days prior to screening. Edaravone is approved by the FDA and in Japan, but remains an investigational product in Europe and Australia
11. Clinically significant history of unstable or severe cardiac, oncological, psychiatric, hepatic, or renal disease or other medically significant illness
12. Taking medication contraindicated with Triumeq: dofetilideor fampridine (dalfampridine)
Sponsor
King's College London, Macquarie University, Stichting TRICALS Foundation
Source: https://www.isrctn.com/
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