IGHTHOUSE II

Phase 1

Active, not recruiting

Conditions: Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-005069-15-SI

Lead Sponsor: Stichting TRICALS Foundation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 390

Inclusion Criteria

1. Age = 18 years at the time of screening
2. Diagnosis of ALS according to the Gold Coast Criteria (Please see Table 1 of Shefner et al Clinical Neurophysiology 2020, also available in Appendix 2)
3. Capable of providing informed consent and complying with trial procedures
4. TRICALS risk profile > -6.0 and < -2.0 (See Section 4.3.4)
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. For more information, please refer to the HMA CTFG Guidelines: https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80N-5ME6pkBb1UHvFsTwqlQ
7. Women of childbearing potential must have a negative serum pregnancy test at screening and baseline 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 (https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf?fbclid=IwAR3AY5Ha0ESDyqIBeUaYI9VTFWmx9bbt8NZ-80N-5ME6pkBb1UHvFsTwqlQ).
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
9. Participant 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 supplementaiton 30 days prior randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

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:
ALT = 5 times upper limit of normal (ULN)
AST = 3 times ULN
Bilirubin = 1.5 times ULN
Creatinine clearance < 30 mL / min
Platelet concentration of < 100 x109 per L
Absolute neutrophil count of < 1x109 per L
Haemoglobin < 100 g/L
Amylase & lipase = 2 times ULN
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)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine if Triumeq improves survival in patients with ALS;Secondary Objective: To determine if Triumeq improves secondary outcomes and selected biomarkers compared with placebo.;Primary end point(s): The primary endpoint is overall survival, defined as time to mortality from any cause<br><br><br>;Timepoint(s) of evaluation of this end point: Up to Month 24

Secondary Outcome Measures