Lighthouse II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting TRICALS Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11], Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Jul 2021 → 26 Mar 2025

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-517054-94-00

EudraCT number

2020-005069-15

ClinicalTrials.gov

NCT05193994

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective of this study is to assess the efficacy of Triumeq versus placebo on overall survival, defined as death from any cause, in participants with ALS at 24 months or after a minimum of 212 events.

Secondary objectives 10

1. To assess the effect of Triumeq versus placebo on a combined assessment of survival and measures of daily functioning (CAFS)
2. To assess the effect of Triumeq versus placebo on measures of daily functioning
3. To assess the effect of Triumeq versus placebo on respiratory function
4. To assess the effect of Triumeq versus placebo on plasma creatinine
5. To assess the effect of Triumeq versus placebo on the time to reach advanced disease stages
6. To evaluate the safety of Triumeq administered orally to participants with ALS
7. To evaluate the tolerability of Triumeq administered orally to participants with ALS
8. To assess the effect of Triumeq versus placebo on change in cognitive functioning
9. To assess the effect of Triumeq versus placebo on change in quality of life
10. To collect research blood and urine samples for post-trial explanatory analyses; markers will be included e.g. urinary P75ECD, plasma neurofilament light and heavy chain, HERV-K and genotyping

Conditions and MedDRA coding

AMYOTROPHIC LATERAL SCLEROSIS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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 1)
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
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
8. For participants taking antacids (regularly or as required), participant is willing and able to avoid taking antacids for at least 6 hours before and 2 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

Exclusion criteria 13

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 with clinical indicators of liver disease, Creatinine clearance < 30 mL / min, Platelet concentration of < 100 x109 per L, Absolute neutrophil count of < 1x109 per L, Haemoglobin < 100 g/L, Amylase ≥ 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
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is overall survival, defined as time to mortality from any cause

Secondary endpoints 10

1. Combined assessment of survival and measures of daily functioning using the ALSFRS-R(30) total score (CAFS)
2. Daily functioning using the ALSFRS-R(30) total score
3. Respiratory function measured by vital capacity (VC) (% predicted of normal according to the GLI-2012 reference standard(37))
4. Plasma creatinine levels
5. Clinical disease stage, defined as mean time spent in each stage of the King’s Staging Scale and the ALS Milano-Torino staging systems (36) (MITOS, derived from ALSFRS-R(30))
6. Safety based on the safety assessments including physical examinations, clinical laboratory evaluations, vital signs and frequency of adverse events (AEs) or serious adverse events (SAEs). (S)A Es will be categorized according seriousness, causality (by study medication), severity and expectedness (as defined in the Triumeq Summary of Product Characteristics)
7. Tolerabilty, as defined by study medication discontinuation
8. Cognitive function, defined as the total scores on the ECAS(32)
9. Quality of life, defined as total scores on the Visual Analogue Scale (single-item scale) and EQ-5D-5L(35)
10. Laboratory parameters e.g. Urine P75ECD, plasma neurofilament light and heavy chain, HERV-K expression and genotyping (UNC13a / C9orf72)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting TRICALS Foundation

Sponsor organisation

Stichting TRICALS Foundation

Address

Goeman Borgesiuslaan 77

City

Utrecht

Postcode

3515 ET

Country

Netherlands

Scientific contact point

Organisation

Stichting TRICALS Foundation

Contact name

Kiki van den Brule

Public contact point

Organisation

Stichting TRICALS Foundation

Contact name

Kiki van den Brule

Locations

5 EU/EEA countries · 7 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 18 files

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

Application history

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