Amyotrophic Lateral SclerosisPhase 1NCT06307301
Study in ALS With Abatacept & IL-2
A Phase 1 study testing Abatacept Injection [Orencia] and Proleukin (aldesleukin) in people with Amyotrophic Lateral Sclerosis, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Abatacept Injection [Orencia] and Proleukin (aldesleukin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2021to 31 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for initial enrollment on this study if they meet the following criteria at the time of screening:
- Provided informed consent and authorized use of protected health information (PHI) in accordance with national and local patient privacy regulations.
- ALS meeting El Escorial criteria for possible, probable, lab-supported probable, or definite ALS.
- At least 18 years old.
- Total bilirubin less than or equal to 1.5 mg/dL
- Alanine aminotransferase level (ALT) less than or equal to five times normal, albumin greater than or equal to 3.0 gm/dL
Show all 12Show fewer
- Serum creatinine less than 1.5 mg/dL
- Capable of complying with all study procedures, including the study drug delivery procedure, in the Investigator's opinion.
- A family member or caretaker who is expected to be consistently available to administer both study drugs of abatacept and IL-2 if the participant is unable to do so.
- On a stable regimen of riluzole for at least 30 days at the time of screening. If not on riluzole at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
- Patients on edaravone willing to refrain from taking edaravone on the same day as they will receive the abatacept injection for the duration of the trial. If not on edaravone at the time of study entry, willing to refrain from initiation of the agent for the duration of the trial.
- Forced vital capacity (FVC) ≥50% of predicted capacity for age, height, and sex at screening, or receiving treatment with noninvasive ventilation if FVC < 50% of predicted for age, height, and sex at screening.
Who cannot join
- Patients will be ineligible to participate if any of the following are true at the time of screening:
- Serious, active bacterial, fungal, or viral infection, active or latent tuberculosis.
- Tracheostomy.
- Severe cardiac dysfunction defined as left ventricular ejection fraction <40% if an echocardiogram is medically indicated to clarify ongoing symptoms or EKG findings.; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months.
- Hypersensitivity or allergy to IL-2 or abatacept.
- History of bowel ischemia/perforation, or GI bleeding requiring surgery.
Show all 13Show fewer
- History of resistant seizures, history of coma or toxic psychosis lasting >48 hours.
- Platelets <100,000/mm3; hematocrit <30%.
- History of cancer in the past 5 years (except cutaneous Basal cell carcinoma or squamous cell carcinoma).
- Hx of immunomodulation therapy including IL-2 or abatacept administration in the past 90 days.
- Treatment with another investigational drug, biological agent, or device within 30 days or 5 half-lives of screening, whichever is longer.
- If female, breastfeeding, known to be pregnant, planning to become pregnant during the study, or unwilling to use effective contraception for the duration of the trial and for 90 days after treatment.
- If male of reproductive capacity, unwilling to use effective contraception for the duration of the trial and for 90 days after treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
Houston Methodist Research Institute
Houston, Texas, 77030
About this study
Official title: A Phase I Trial to Evaluate Safety and Tolerability of Abatacept Followed by Subcutaneous Interleukin-2 Administration in Patients With Amyotrophic Lateral Sclerosis
In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients, which showed enhancement of Treg numbers and suppressive function in vivo. The enhanced Treg suppressive function correlated strongly with slowing and stabilization of disease progression. Drugs that enhance endogenous Treg numbers and suppressive function may also stabilize disease in ALS. This phase 1 study aims to determine whether the combination therapy of subcutaneous IL-2 and abatacept (Orencia®) is safe and well-tolerated in 6 patients with ALS, and whether the therapy enhances Treg numbers and suppressive function in vivo.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Abatacept Injection [Orencia] and Proleukin (aldesleukin)
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abatacept Injection [Orencia] and Proleukin (aldesleukin)Drug
Abatacept (Orencia®) and recombinant human IL-2 (aldesleukin). Patients will receive a fixed dose of subcutaneous abatacept (125 mg/mL) at day 1. Two weeks later (day 15), patients will receive the second dose of subcutaneous abatacept (125 mg/mL). In addition, patients will receive subcutaneous IL-2 (1x106units /day) for 5 days (days 15-19). If this treatment regimen is tolerated, patients will receive 28 further similar treatment courses of abatacept and IL-2 every two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Phase I Study in ALS with Abatacept & IL-2 | Experimental | Primary Objective:
1. To assess the safety and the tolerability of abatacept followed by IL-2 administration in ALS patients
Secondary Objectives:
1. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the number of Tregs
2. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the suppressive activity of Tregs on T effector proliferation.
3. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring in the level of cytokines secreted by PBMCs throughout the course of the study
Exploratory Objective:
1. To characterize the effects of abatacept followed by IL-2 on clinical outcome measures of ALS, including the Appel ALS Rating Scale (AALS) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, and the forced vital capacity (FVC) and maximum inspiratory pressure (MIP). Receives: Drug: Abatacept Injection [Orencia] and Proleukin (aldesleukin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients
Incidence and severity of AEs, including changes in laboratory values and vital signs.
The investigator will determine whether safety and tolerability of abatacept followed by IL-2 administration are acceptable in order to proceed with the next phase. Safety and tolerability will be assessed throughout the study.
Measured: 24 months
Secondary outcomes (3)
Change in Regulatory T cells (Tregs) numbers in the blood from baseline
The change in the number of Tregs.will be monitored
The investigator hypothesizes that increasing Treg numbers and suppressive function will slow the progression of ALS, and the investigator will determine whether these markers increase in response to Abatacept/IL-2 administration.
Measured: Baseline to Week 15
Change in Regulatory T cells (Tregs) suppressive function in the blood from baseline
The change in the suppressive activity of Tregs on responder T cell proliferation will be monitored
The investigator hypothesizes that increasing Treg numbers and suppressive function will slow the progression of ALS, and the investigator will determine whether these markers increase in response to Abatacept/IL-2 administration.
Measured: Baseline to Week 15
Changes in the level of cytokines secreted by PBMCs from baseline
The level of cytokines secreted by PBMCs throughout the course of the study
The investigator hypothesizes that modulating peripheral inflammatory cytokines will slow the progression of ALS, and the investigator will determine whether these markers decrease in response to Abatacept/IL2 administration.
Measured: Baseline to Week 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start28 Oct 2021
- Primary completion31 Dec 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jason Thonhoff, MD, PhD, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06307301
- Sponsor's protocol ID
- PRO00031998
- Status last verified
- Apr 2024
- First submitted
- 26 Dec 2023
- Last updated
- 22 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Thonhoff JR, Beers DR, Zhao W, Faridar A, Thome A, Wen S, Zhang A, Wang J, Appel SH. A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis. Front Neurol. 2024 Jun 10;15:1415106. doi: 10.3389/fneur.2024.1415106. eCollection 2024.
PubMed 38915796
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial to Evaluate Safety and Tolerability of Abatacept Followed by Subcutaneous Interleukin-2 Administration in Patients With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT06307301
- Acronym / sponsor ID
- PRO00031998
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- 28 Oct 2021 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients, which showed enhancement of Treg numbers and suppressive function in vivo. The enhanced Treg suppressive function correlated strongly with slowing and stabilization of disease progression. Drugs that enhance endogenous Treg numbers and suppressive function may also stabilize disease in ALS. This phase 1 study aims to determine whether the combination therapy of subcutaneous IL-2 and abatacept (Orencia®) is safe and well-tolerated in 6 patients with ALS, and whether the therapy enhances Treg numbers and suppressive function in vivo.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I Study in ALS with Abatacept & IL-2 | Experimental | Drug: Abatacept Injection [Orencia] and Proleukin (aldesleukin)Primary Objective: 1. To assess the safety and the tolerability of abatacept followed by IL-2 administration in ALS patients Secondary Objectives: 1. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the number of Tregs 2. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring the change in the suppressive activity of Tregs on T effector proliferation. 3. To investigate the immunomodulatory effects of abatacept followed by IL-2, by monitoring in the level of cytokines secreted by PBMCs throughout the course of the study Exploratory Objective: 1. To characterize the effects of abatacept followed by IL-2 on clinical outcome measures of ALS, including the Appel ALS Rating Scale (AALS) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, and the forced vital capacity (FVC) and maximum inspiratory pressure (MIP). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients will be eligible for initial enrollment on this study if they meet the following criteria at the time of screening:
- Provided informed consent and authorized use of protected health information (PHI) in accordance with national and local patient privacy regulations.
- ALS meeting El Escorial criteria for possible, probable, lab-supported probable, or definite ALS.
- At least 18 years old.
- Total bilirubin less than or equal to 1.5 mg/dL
Key exclusion criteria (13 listed)
- Patients will be ineligible to participate if any of the following are true at the time of screening:
- Serious, active bacterial, fungal, or viral infection, active or latent tuberculosis.
- Tracheostomy.
- Severe cardiac dysfunction defined as left ventricular ejection fraction <40% if an echocardiogram is medically indicated to clarify ongoing symptoms or EKG findings.; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months.
- Hypersensitivity or allergy to IL-2 or abatacept.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Abatacept Injection [Orencia] and Proleukin (aldesleukin)Abatacept (Orencia®) and recombinant human IL-2 (aldesleukin). Patients will receive a fixed dose of subcutaneous abatacept (125 mg/mL) at day 1. Two weeks later (day 15), patients will receive the second dose of subcutaneous abatacept (125 mg/mL). In addition, patients will receive subcutaneous IL-2 (1x106units /day) for 5 days (days 15-19). If this treatment regimen is tolerated, patients will receive 28 further similar treatment courses of abatacept and IL-2 every two weeks. | Drug | Phase I Study in ALS with Abatacept & IL-2 |
Primary outcome
To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients
Time frame: 24 months
Incidence and severity of AEs, including changes in laboratory values and vital signs. The investigator will determine whether safety and tolerability of abatacept followed by IL-2 administration are acceptable in order to proceed with the next phase. Safety and tolerability will be assessed throughout the study.
3 secondary outcomes
Change in Regulatory T cells (Tregs) numbers in the blood from baseline
Time frame: Baseline to Week 15
Change in Regulatory T cells (Tregs) suppressive function in the blood from baseline
Time frame: Baseline to Week 15
Changes in the level of cytokines secreted by PBMCs from baseline
Time frame: Baseline to Week 15
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Derived from this study: PubMed 38915796Thonhoff JR, Beers DR, Zhao W, Faridar A, Thome A, Wen S, Zhang A, Wang J, Appel SH. A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis. Front Neurol. 2024 Jun 10;15:1415106. doi: 10.3389/fneur.2024.1415106. eCollection 2024.
Related trials for Amyotrophic Lateral Sclerosis
Not yet recruitingPhase 1
A Study of Single Ascending Doses of NI112 in Adults With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
MindEx: A Novel, Multifocal, Cognitive Brain-Machine Interface System
Paralysis; Quadriplegic, Quadraplegia
RecruitingPhase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Amyotrophic Lateral Sclerosis
RecruitingObservational study
Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Recruiting
Anticipated Patient and Caregiver Burden
Amyotrophic Lateral Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Thonhoff, MD, PhD principal investigator
The Methodist Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Abatacept Injection [Orencia] and Proleukin (aldesleukin) in people with Amyotrophic Lateral Sclerosis, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06307301, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.