HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 January 2023
• Main ID: NCT02437110
• Date of registration: 05/05/2015
• Prospective Registration: Yes
• Primary sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Public title: HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: HERV-K Suppression Using Antiretroviral Therapy in Volunteers With Amyotrophic Lateral Sclerosis (ALS)
• Date of first enrolment: April 1, 2019
• Target sample size: 122
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02437110
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Avindra Nath, M.D.
• Affiliation: National Institute of Neurological Disorders and Stroke (NINDS)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

Subjects must meet all of the following inclusion criteria to be eligible to participate in
this study:

- Age 18 years or older at the time of the screening visit.

- Able to provide informed consent and comply with study procedures.

- ALS diagnosed as probable, laboratory-supported probable or definite according to the
World Federation of Neurology El Escorial revised criteria32 as determined by a
neurologist with neuromuscular subspecialty training.

- A ratio of HERV-K:RPP greater than or equal to 13 measured by quantitative PCR at the
screening visit.

- Duration of disease less than 2 years, or if greater than 2 years, disease progression
at a rate that in the judgement of the investigator would allow for completion of the
study.

- If taking riluzole or edaravone, must be on a stable dose for at least 30 days prior
to the screening visit, or stopped taking riluzole or edaravone at least 30 days prior
to the screening visit.

- Subject has a competent caregiver who can and will be responsible for administering
study drug. If there is no caregiver, another qualified individual must be available
to do this.

- Subject has established care with a neurologist and will maintain this clinical care
throughout the study.

- Subject has had neuroimaging within the last 24 months for participants enrolling at
the NIH Clinical Center.

EXCLUSION CRITERIA:

A participant will be excluded if he or she has any of the following:

- Dependence on daytime mechanical ventilation (invasive or non-invasive, including
Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPap)
at the time of the screening visit.

- Participation in any other investigational drug trial or using investigational drug
(within 4 weeks prior to the Day 0 visit and thereafter).

- History of severe sulfonamide allergy (i.e. anaphylaxis).

- History of positive test or positive result at screening for HIV or HTLV-1.

- Participants must not be able to become pregnant (e.g., post-menopausal for at least
one year, surgically sterile, or using adequate methods of contraception) or
breastfeed for the duration of the study. Adequate methods of contraception include:
implanted contraception, intrauterine device in place for at least 3 months, or
barrier method in conjunction with spermicide. Participants of

childbearing potential must have a negative pregnancy test at screening and be
non-lactating.

- Presence of any of the following clinical conditions at the time of screening:

- Drug abuse or alcoholism

- Unstable medical disease (such as unstable angina or chronic obstructive
pulmonary disease), or active infectious disease (such as Hepatitis C or
tuberculosis), or current malignancy

- Unstable psychiatric illness defined as psychosis or untreated major depression
within 90 days of the screening visit

- Dementia

- Diabetes mellitus

- Hemophilia

- Use of contraindicated medications: amiodarone, dronedarone, lovastatin, simvastatin,
rifampin, rifapentine, rifabutin, cisapride, pimozide, midazolam, triazolam,
dihydroergotamine, ergonovine, ergotamine, methylergonovine, St. John s wort,
alfuzosin, salmeterol, sildenafil for pulmonary arterial hypertension, oxcarbazepine,
phenobarbital, phenytoin or dofetilide.

- Safety Laboratory Criteria at the screening visit:

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than
3.0 times the upper limit of normal

- Serum creatinine, serum phosphorous, total bilirubin, triglycerides, amylase, or
lipase greater than 2.0 times the upper limit of normal

- Estimated glomerular filtration rate <60mg/dl.

- Platelet concentration of <100,000/ (micro)l.

- PT and PTT >1.2 times the upper limit of normal for participants enrolling at the
NIH Clinical Center.

- Hemoglobin <10mg/dL.

- Positive Hepatitis B Surface Antigen and Hepatitis C Virus Antigen



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: Dolutegravir

Drug: Tenofovir alafenamide (TAF)

Drug: Darunavir

Drug: Ritonavir

Primary Outcome(s)

The primary objective is to assess whether an antiretroviral regimen of darunavir + ritonavir, dolutegravir, and TAF for 24 weeks will suppress blood levels of HERV-K RNA below the limit of detection (1000 copies/ml) in patients with HERV-K-posi... [Time Frame: One Year]

Secondary Outcome(s)

The secondary objective of this study is to assess the safety of an antiretroviral regimen of darunavir + ritonavir, dolutegravir, and TAF in patients with ALS. [Time Frame: Each study visit through week 36]

Secondary ID(s)

150126

15-N-0126

Source(s) of Monetary Support

Please refer to primary and secondary sponsors