Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Lou Gehrig's Disease, motor neuron disease, motor neuron degeneration, AT-1501, humanized blocking antibody to CD40LG, CD40L inhibitor, monoclonal antibody
Brief summary
This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40 ligand (CD40L). Approximately 54 adults with Amyotrophic Lateral Sclerosis (ALS) will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites. Participants will be enrolled into one of four ascending doses.
Detailed description
This is a Phase 2a, multi-center, open label, multiple dose study of AT-1501, a humanized monoclonal antibody antagonist to CD40L. Approximately 54 adults with ALS will be enrolled into the study in the United States and Canada at approximately 13 ALS treatment sites. Four ascending doses of AT-1501 will be administered as an IV infusion to sequentially enrolling cohorts. Each participant will receive 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period. The study is estimated to take 19 weeks for participants.
Interventions
DRUGAT-1501
AT-1501 monoclonal antibody targeting CD40L given as an IV infusion
Sponsors
Anelixis Therapeutics, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ALS diagnosed as possible, laboratory supported probable, probable, or definite as defined by revised El Escorial criteria 2. ALS Functional Rating Scale - Revised (ALSFRS-R) Aggregate score of 37 or greater 3. No more than 24 months from diagnosis
Exclusion criteria
1. Any other central or peripheral nervous system disease that may interfere with the evaluation of ALS or its progression 2. Presence of a tracheostomy, or use of permanent assistive ventilation (ventilatory support for 23 hours per day or more) 3. History of malignancy within the previous 5 years, except for localized non-melanoma skin cancers 4. Abnormal function of the immune system resulting from: * Clinical conditions affecting the immune system (e.g. HIV infection, agammaglobulinemia), * Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to 20 mg/day of prednisone for more than 14 consecutive days within 90 days prior to screening, * Administration of anti-neoplastic and/or immunomodulating agents (e.g. Tumor necrosis factor alpha (TNF α) antagonists or anti-B cell antibodies) or radiotherapy within 1 year prior to screening. 5. Recipient of Stem Cell or Gene Therapy 6. Positive test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV. 7. History of deep venous thrombosis or pulmonary embolism 8. History of active substance abuse within the past 2 years 9. History of stroke, poorly controlled or significant cardiovascular disease, diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Up to 18 Weeks | Incidence of adverse events (AEs) reported as number of participants with at least one TEAE (Treatment Emergent Adverse Event) and at least one SAE (Serious Adverse Event). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AT-1501 1.0 mg/kg This group received a 1.0 mg/kg dose administered as an 1-hour IV infusion. Each participant received 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period. | 9 |
| AT-1501 2.0 mg/kg This group received a 2.0 mg/kg dose administered as an 1-hour IV infusion. Each participant received 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period. | 9 |
| AT-1501 4.0 mg/kg This group received a 4.0 mg/kg dose administered as an 1-hour IV infusion. Each participant received 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period. | 18 |
| AT-1501 8.0 mg/kg This group received a 8.0 mg/kg dose administered as an 1-hour IV infusion. Each participant received 6 bi-weekly (every other week) infusions of AT-1501 over an 11-week period. | 18 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 |
| Overall Study | Undergoing cancer treatment & was unable to return to site to complete EOS visit within window | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | AT-1501 2.0 mg/kg | AT-1501 4.0 mg/kg | AT-1501 1.0 mg/kg | AT-1501 8.0 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 2 Participants | 7 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 15 Participants | 7 Participants | 11 Participants | 39 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 14.76 | 56.4 years STANDARD_DEVIATION 8.53 | 61.2 years STANDARD_DEVIATION 6.5 | 60.3 years STANDARD_DEVIATION 11.11 | 59 years STANDARD_DEVIATION 10.29 |
| ALSFRS-R Subdomain at Baseline Dyspnea | 3.7 units on a scale STANDARD_DEVIATION 0.5 | 3.6 units on a scale STANDARD_DEVIATION 0.85 | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.8 units on a scale STANDARD_DEVIATION 0.55 | 3.7 units on a scale STANDARD_DEVIATION 0.62 |
| ALSFRS-R Subdomain at Baseline Orthopnea | 3.8 units on a scale STANDARD_DEVIATION 0.67 | 3.8 units on a scale STANDARD_DEVIATION 0.38 | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.9 units on a scale STANDARD_DEVIATION 0.24 | 3.9 units on a scale STANDARD_DEVIATION 0.37 |
| ALSFRS-R Subdomain at Baseline Respiratory Insufficiency | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.9 units on a scale STANDARD_DEVIATION 0.47 | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.7 units on a scale STANDARD_DEVIATION 0.59 | 3.9 units on a scale STANDARD_DEVIATION 0.45 |
| ALSFRS-R Subdomain at Screening Dyspnea | 3.8 units on a scale STANDARD_DEVIATION 0.44 | 3.7 units on a scale STANDARD_DEVIATION 0.59 | 4 units on a scale STANDARD_DEVIATION 0 | 3.8 units on a scale STANDARD_DEVIATION 0.43 | 3.8 units on a scale STANDARD_DEVIATION 0.46 |
| ALSFRS-R Subdomain at Screening Orthopnea | 3.8 units on a scale STANDARD_DEVIATION 0.67 | 3.9 units on a scale STANDARD_DEVIATION 0.32 | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.9 units on a scale STANDARD_DEVIATION 0.24 | 3.9 units on a scale STANDARD_DEVIATION 0.35 |
| ALSFRS-R Subdomain at Screening Respiratory Insufficiency | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.9 units on a scale STANDARD_DEVIATION 0.47 | 4.0 units on a scale STANDARD_DEVIATION 0 | 3.7 units on a scale STANDARD_DEVIATION 0.57 | 3.9 units on a scale STANDARD_DEVIATION 0.44 |
| ALSFRS-R Total Score at Baseline | 40.0 units on a scale STANDARD_DEVIATION 2 | 39.6 units on a scale STANDARD_DEVIATION 3.99 | 40.4 units on a scale STANDARD_DEVIATION 3.17 | 38.6 units on a scale STANDARD_DEVIATION 3.96 | 39.5 units on a scale STANDARD_DEVIATION 3.56 |
| ALSFRS-R Total Score at Screening | 40.2 units on a scale STANDARD_DEVIATION 1.92 | 39.7 units on a scale STANDARD_DEVIATION 3.69 | 41.1 units on a scale STANDARD_DEVIATION 3.02 | 39.2 units on a scale STANDARD_DEVIATION 2.65 | 39.9 units on a scale STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 18 Participants | 9 Participants | 15 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 17 Participants | 9 Participants | 18 Participants | 52 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 3 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 6 Participants | 10 Participants | 35 Participants |
| Time Since ALS Diagnosis | 101.6 days STANDARD_DEVIATION 75.32 | 244.8 days STANDARD_DEVIATION 204.4 | 251.9 days STANDARD_DEVIATION 241.52 | 219.1 days STANDARD_DEVIATION 174.57 | 231.5 days STANDARD_DEVIATION 188.57 |
| Time Since ALS Symptom Onset | 647.2 days STANDARD_DEVIATION 388.67 | 705.0 days STANDARD_DEVIATION 580.3 | 610.2 days STANDARD_DEVIATION 340.2 | 631.4 days STANDARD_DEVIATION 431.02 | 655.1 days STANDARD_DEVIATION 457.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 8 / 9 | 8 / 9 | 10 / 18 | 16 / 18 |
| serious Total, serious adverse events | 0 / 9 | 1 / 9 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Safety and Tolerability
Incidence of adverse events (AEs) reported as number of participants with at least one TEAE (Treatment Emergent Adverse Event) and at least one SAE (Serious Adverse Event).
Time frame: Up to 18 Weeks
Population: Full analysis set. All enrolled patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AT-1501 1.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One TEAE | 8 participants |
| AT-1501 1.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One SAE | 0 participants |
| AT-1501 2.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One SAE | 1 participants |
| AT-1501 2.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One TEAE | 8 participants |
| AT-1501 4.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One TEAE | 10 participants |
| AT-1501 4.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One SAE | 0 participants |
| AT-1501 8.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One TEAE | 16 participants |
| AT-1501 8.0 mg/kg | Safety and Tolerability | Number of Subjects with at Least One SAE | 0 participants |
Primary
Safety and Tolerability
Incidence of adverse events (AEs) reported as number of TEAEs (Treatment Emergent Adverse Events) having occurred.
Time frame: Up to 18 Weeks
Population: Full analysis set. All enrolled patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AT-1501 1.0 mg/kg | Safety and Tolerability | 30 TEAEs |
| AT-1501 2.0 mg/kg | Safety and Tolerability | 66 TEAEs |
| AT-1501 4.0 mg/kg | Safety and Tolerability | 54 TEAEs |
| AT-1501 8.0 mg/kg | Safety and Tolerability | 67 TEAEs |