Trial Outcomes & Findings for N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T) (NCT NCT03759678)

Last Updated: 2026-03-25

Results Overview

The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video? The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse). Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)). Then, the mean change obtained in the post-treatment period was subtracted from the mean change obtained for the treatment with IB1001 period, with a positive value indicating an improvement in the treatment period compared to the post-treatment washout period.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

CI-CS comparing Baseline (Day 1) with IB1001 versus the end of 6-weeks treatment with IB1001 (Approximately Day 42) MINUS the CI-CS comparing the end of 6-weeks treatment with IB1001 (Approximately Day 42) versus the end of 6-weeks post-treatment washout

Results posted on

2026-03-25

Participant Flow

All patients began treatment with N-Acetyl-L-Leucine (IB1001) in this open-label study schema. In the parent study, the post-treatment washout period followed the IB treatment period. After the parent study, patients could enter an extension phase.

Participant milestones

Participant milestones
Measure	Parent Study 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took take 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Treatment with IB1001 STARTED	17
Treatment with IB1001 COMPLETED	16
Treatment with IB1001 NOT COMPLETED	1
Post-Treatment Washout STARTED	16
Post-Treatment Washout COMPLETED	16
Post-Treatment Washout NOT COMPLETED	0
Extension Phase STARTED	13
Extension Phase COMPLETED	10
Extension Phase NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Parent Study 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took take 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Treatment with IB1001 Adverse Event	1
Extension Phase Adverse Event	1
Extension Phase Withdrawal by Subject	1
Extension Phase Lost to Follow-up	1

Baseline Characteristics

N-Acetyl-L-Leucine for Ataxia-Telangiectasia (A-T)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parent Study n=17 Participants All patients were first dosed with IB1001.Therefore, the baseline characteristics of patients dosed in the first IB1001treatment period in the parent study constitute the baseline characteristics for the entire study.
Age, Continuous	23.3 Years STANDARD_DEVIATION 12.9 • n=138 Participants
Sex: Female, Male Female	7 Participants n=138 Participants
Sex: Female, Male Male	10 Participants n=138 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=138 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=138 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=138 Participants

PRIMARY outcome

Timeframe: CI-CS comparing Baseline (Day 1) with IB1001 versus the end of 6-weeks treatment with IB1001 (Approximately Day 42) MINUS the CI-CS comparing the end of 6-weeks treatment with IB1001 (Approximately Day 42) versus the end of 6-weeks post-treatment washout

Population: Modified Intention to Treat (mITT) Analysis Set is defined as all patients who receive at least one dose of the study drug and with one video recording during the baseline period (Visit 1 or 2, or both) and treatment period (Visit 3 or Visit 4, or both).

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Clinical Impression of Change in Severity (CI-CS) [Fields et al. 2021]	0.16 Score on a scale Standard Deviation 1.65

SECONDARY outcome

Timeframe: (CI-S comparing baseline period [average for Visit 1 and 2] and end of treatment period [average for Visit 3 and 4]) MINUS (change in CI-S between end of treatment period [average for Visit 3 and 4] and end of washout period [average for Visit 5 and 6])

The Change in Severity assessment will instruct the blinded rater to consider the severity of the patient at each visit. The Clinical Impression of Severity (CI-S)-assessment ranged from +3 ="normal not ill at all" to -3="among the most extremely ill patients ". Change values were calculated for each period, i.e. treatment with IB1001 (change between the baseline period \[average for Visit 1 and Visit 2\] and end of treatment period \[average for Visit 3 and Visit 4\]) and post-treatment washout (between end of treatment period \[average for Visit 3 and Visit 4\] and end of washout period \[average for Visit 5 and Visit 6\]). Then, the mean change in the post-treatment period was subtracted from the mean change in the treatment with IB1001 period.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Key Secondary Endpoint: Change in Severity Based on Average CI-S	-0.09 Score on a scale Standard Deviation 0.39

SECONDARY outcome

Timeframe: Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: Individual Components of CI-CS Treatment with IB1001	0.16 Score on a scale Standard Deviation 0.81
Secondary Efficacy Endpoint: Individual Components of CI-CS Post-Treatment Washout	0.00 Score on a scale Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline to end of treatment with IB1001 (Parent Study 6-weeks treatment); End of treatment with IB1001 to the end of post 6-week treatment washout

The Clinical Impression of Change in Severity assessment will instruct the blinded rater to consider: compared to the first video, how has the severity of their performance on the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or 8 Meter Walk Test (8MWT) changed (improved or worsened) in 6-weeks as observed in the second video? The Clinical Impression of Change in Severity is evaluated on a 7 point Likert scale (+3=significantly improved to -3= significantly worse). CI-CS scores \<0 were reclassified as worsened (-1), CI-CS scores 0 remained classified as not changed (0), and CI-CS scores \>0 were reclassified as improved (+1). When comparing Visit 4 versus Visit 2 and Visit 6 versus Visit 4, CI-CS scores \<0 were reclassified as worsened (-1), CI-CS scores 0 remained classified as not changed (0), and CI-CS scores \>0 were reclassified as improved (+1).

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Treatment with IB1001 · -1 (Worsened)	6 Participants
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Treatment with IB1001 · 0 (No Observable Change)	2 Participants
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Treatment with IB1001 · +1 (Improved)	8 Participants
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Post-treatment washout · -1 (Worsened)	7 Participants
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Post-treatment washout · 0 (No Observable Change)	1 Participants
Secondary Efficacy Endpoint: CI-CS Score Reclassified on a 3-Point Scale Post-treatment washout · +1 (Improved)	8 Participants

SECONDARY outcome

Timeframe: CI-CS of the non-primary anchor test was evaluated, comparing the CI-CS of Visit 4 (end of treatment) versus Visit 2 (baseline) and of Visit 6 (end of washout) versus Visit 4 (end of treatment) as done for the primary anchor test.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: CI-CS Score for the Non-Primary Anchor Test Treatment with IB1001	0.00 Score on a scale Standard Deviation 1.07
Secondary Efficacy Endpoint: CI-CS Score for the Non-Primary Anchor Test Post-treatment washout	0.17 Score on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84)

The Scale for Assessment and Rating of Ataxia has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements, and heel-shin test. The range is 0-40 points, with a lower score representing neurological improvement and a higher score representing neurological worsening. Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)).

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: Change in the Scale for Assessment and Rating of Ataxia (SARA) Score [Schmitz-Hübsch Etal, 2006; Subramony, 2007] Treatment with IB1001	-0.31 Score on a scale Standard Deviation 3.47
Secondary Efficacy Endpoint: Change in the Scale for Assessment and Rating of Ataxia (SARA) Score [Schmitz-Hübsch Etal, 2006; Subramony, 2007] Post-treatment washout	0.59 Score on a scale Standard Deviation 2.99

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84)

Spinocerebellar Ataxia Functional Index (SCAFI) is composed of 8 Meter Walk Test, 9-Hole Peg Test of Dominant and Non-Dominant Hand (9HPT-D/9HPT-ND) (the 3 tests are timed assessments; each is done twice and values are averaged; the 8MWT and 9HPT-D and 9HPT-ND values are converted from times to rates, and the results expressed as a composite Z-score of each test relative to baseline) and the PATA rate (counted number how often a patient can repeat the syllables "PATA" within 10 seconds), a measure of speech performance. The scores of these 3 were transformed to Z-scores (=individual's average of both trials to perform the respective task -mean of study population at baseline) / SD of study population at baseline). A Z-score of 0 equates to the population mean at baseline. For all 3, higher Z-scores (above mean) mean better performance. The SCAFI total score was calculated as the arithmetic mean of the non-missing Z-scores for the 3. A higher total score means better performance.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: Spinocerebellar Ataxia Functional Index (SCAFI) [Schmitz-Hübsch et al, 2008] Treatment with IB1001	0.0583 Score on a scale Standard Deviation 0.3384
Secondary Efficacy Endpoint: Spinocerebellar Ataxia Functional Index (SCAFI) [Schmitz-Hübsch et al, 2008] Post-treatment washout	0.0157 Score on a scale Standard Deviation 0.1923

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84)

For posting, health-related quality of life based on the EQ-5D visual analogue scale (VAS) was presented as a secondary endpoint. EQ-5D VAS is a 0-100 scale where patients are asked to indicate their overall health, with a score of 0 indicating worst health and a score of 100 indicating best health.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale Treatment with IB1001	4.9 Score on a scale Standard Deviation 9.7
Secondary Efficacy Endpoint: EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale Post-treatment washout	-0.8 Score on a scale Standard Deviation 10.5

SECONDARY outcome

Timeframe: Visits of Parent study: Visit 1 (Day -14), Visit 2 (Day 1), Visit 3 (Day 28), Visit 4 (Day 42), Visit 5 (Day 70), and Visit 6 (Day 84).

The Clinical Global Impression of Severity(CGI-S) evaluates the question "Considering your total (clinical) experience with this particular population, how ill is the patient (how ill are you) at this time?" based on answers from the treating physician, the caregiver, or the patients (if able). This was rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill the patient has been/I have ever been.

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 1	4.2 Score on a scale Standard Deviation 1.1
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 2	4.2 Score on a scale Standard Deviation 1.1
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 3	4.0 Score on a scale Standard Deviation 1.1
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 4	4.0 Score on a scale Standard Deviation 1.1
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 5	4.1 Score on a scale Standard Deviation 1.0
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Treating physician: Visit 6	4.1 Score on a scale Standard Deviation 0.9
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 1	3.5 Score on a scale Standard Deviation 2.0
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 2	3.1 Score on a scale Standard Deviation 2.0
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 3	3.3 Score on a scale Standard Deviation 1.6
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 4	2.9 Score on a scale Standard Deviation 1.5
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 5	3.3 Score on a scale Standard Deviation 1.7
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Caregiver: Visit 6	3.4 Score on a scale Standard Deviation 1.8
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 1	2.8 Score on a scale Standard Deviation 1.8
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 2	2.3 Score on a scale Standard Deviation 1.6
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 3	2.5 Score on a scale Standard Deviation 1.7
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 4	2.4 Score on a scale Standard Deviation 1.8
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 5	2.9 Score on a scale Standard Deviation 1.8
Secondary Efficacy Endpoint: Clinical Global Impression of Severity (Treating Physician, Caregiver, Patient) Patient: Visit 6	2.9 Score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84)

The Clinical Global Impression of Change assessed by the investigator is evaluated on a 7 point Likert scale ranging from 1='very much improved' to 7='very much worse' Change values were calculated for each period, i.e. treatment with IB1001 (comparing the end of treatment (Visit 4) with baseline (Visit 2)) and post-treatment washout (comparing the end of washout (Visit 6) with the end of treatment (Visit 4)).

Outcome measures

Outcome measures
Measure	Parent Study n=16 Participants 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Caregiver: Post-treatment washout	4.7 Score on a scale Standard Deviation 1.0
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Treating physician: Treatment with IB1001	3.3 Score on a scale Standard Deviation 0.9
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Treating physician: Post-treatment washout	4.8 Score on a scale Standard Deviation 0.9
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Caregiver: Treatment with IB1001	3.1 Score on a scale Standard Deviation 0.8
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Patient: Treatment with IB1001	3.5 Score on a scale Standard Deviation 0.9
Secondary Efficacy Endpoint: Clinical Global Impression of Change (Treating Physician, Caregiver, Patient) Patient: Post-treatment washout	4.7 Score on a scale Standard Deviation 1.1

Adverse Events

Treatment With IB1001

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Post-treatment Washout

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Extension Phase

Serious events: 2 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment With IB1001 n=17 participants at risk Parent Study: 6-weeks treatment with IB1001 administered orally. Patients ≥13 years old received a total daily dose of 4 g/day (administered as 3 doses per day). Patients 6-12 years old received weight-tiered doses: * Patients aged 6-12 years weighing 15 to \<25 kg took 2g per day: 1 g in the morning and 1 g in the evening. * Patients aged 6-12 years weighing 25 to \<35 kg took take 3g per day: 1 g in the morning, 1g in the afternoon, and 1 g in the evening. * Patients aged 6-12 years weighing ≥35 kg took 4 g per day: 2 g in the morning, 1g in the afternoon and 1 g in the evening (as per adults). IB1001: IB1001 (N-Acetyl-L-Leucine) is a modified amino-acid ester that is orally administered. After the 6-week treatment period, patients entered a 6-week post-treatment washout period.	Post-treatment Washout n=17 participants at risk After the Parent Study 6-week treatment period, patients entered a 6-week post-treatment washout period.	Extension Phase n=13 participants at risk Patients who completed the Parent Study were to be offered the opportunity to participate in the Extension Phase if the investigator determined it was in their best interest. Patients received treatment with IB1001 for two one-year treatment periods, separated by a 6-week washout. All patients received the study drug during the treatment periods. Patients who completed Visit 6 of the parent study and continued into the Extension Phase were assessed approximately 6 times over a 116-week period.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal lymphoma	5.9% 1/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Infections and infestations Infection	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Infections and infestations Mastitis	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Injury, poisoning and procedural complications Seroma	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal mesothelioma malignant	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	0.00% 0/17 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.	7.7% 1/13 • For the parent study (treatment with IB1001 and Post-treatment washout): from signing of the informed consent form through to End of Study (Day 84, scheduled at 42 days post last IB1001dose); For the extension phase: from signing of the extension phase informed consent form through to End of Study for the extension phase (Day 767). Adverse events (AEs) / serious adverse events (SAEs) consistent with the definition from ClinicalTrial.Gov. AEs/SAEs were collected in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-CGP). All patients were naïve, so a separate arm for non-naive participants who needed a 6-weeks washout prior to starting treatment, could not be evaluated separately.

Other adverse events

Additional Information

Taylor Fields, Chief Product Development Officer

Intrabio Ltd

Phone: +44 8081

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place