Safety, Tolerability and Pharmacokinetics Study of STP1 in a Subgroup of Patients With Autism Spectrum Disorder

A Phase 1b, Double-Blind, Placebo-Controlled, First-in-Human Study to Evaluate Safety, Tolerability and Pharmacokinetics of a Two-Week Oral Treatment With STP1 in a Subgroup of Patients With Autism Spectrum Disorder

The main purpose of this study is to evaluate safety and tolerability, Pharmacokinetics and Pharmacodynamics, as well as exploratory efficacy of STP1, in a subgroup of patients with Autism Spectrum Disorder (ASD).

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: STP1; Drug: Placebo

Detailed Description

After obtaining written informed consent, those patients who are deemed eligible for the study, will be randomized on Day 1, in a double-blinded manner, in a 3:1ratio to receive either oral STP1 (twice daily) or placebo (twice daily). The total study duration is 6 weeks, including a screening phase of up to 2 weeks, a treatment phase of 2 weeks and a post-treatment follow-up phase of 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Male or female individuals, between 18 and 40 years, diagnosed of ASD.
2. Patients will be assessed for specific developmental anthropometric & anatomical criteria as well as personal and family medical history as assessed by the ASD-Phen1 semi structured interview form.
3. Patients must have a parent or reliable caregiver who can provide information about the pre-natal period and early developmental period, as required by the protocol.
4. Patient and/or parent or legal guardian willing and consenting to participate.
5. Patients with ASD and comorbid seizure disorder should be seizure-free for at least 6 months prior to screening.
6. Before enrolling in the study, subjects must agree to use double-barrier birth control methods if they engage in intercourse.

Key Exclusion Criteria:

1. Patients with an identified genetic cause of ASD in their medical record will be excluded from the study.
2. History of traumatic head injury, cerebrovascular disorder, congestive heart failure, hepatic or renal disease.
3. Thrombocytopenia.
4. Type 1 Diabetes Mellitus or uncontrolled type 2 Diabetes Mellitus, or latent autoimmune diabetes of the adult.
5. A significant risk for suicidal behavior.
6. Initiation of, or a major change in psychological / behavioral intervention within 4 weeks prior to randomization.
7. Patient with any active infection.
8. Systolic blood pressure (SBP) <80 mmHg or diastolic blood pressure (DBP) <40 mmHg or a drop in SBP of ≥20 mm Hg, or in DBP of ≥10 mm Hg, during the orthostatic recordings.
9. Clinically relevant electrocardiogram (ECG) abnormalities.
10. Clinically significant abnormal laboratory test.
11. Active clinically significant disease.
12. History of malignancy.
13. Pregnant (confirmed by laboratory testing) or lactating female patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STP1 Low Dose; 1 capsule and 1 tablet per intake	Drug: STP1; STP1 is a combination of two drugs, a PDE inhibitor and an NKCC1 inhibitor
Experimental: STP1 High Dose; 1 capsule and 1 tablet per intake	Drug: STP1; STP1 is a combination of two drugs, a PDE inhibitor and an NKCC1 inhibitor
Placebo Comparator: Placebo; 1 placebo capsule and 1 placebo tablet per intake	Drug: Placebo; Placebo medication (capsule and tablet) identical in appearance to active medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Incidence, nature and severity of adverse events, serious adverse events and adverse events of special interest	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of STP1 (PK)	Standard non-compartmental analysis	Day 1, Day 7, Day 14, Day 15 (and optionally: Day 16, Day 17 and Day 18)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ABC-C: Aberrant Behavior Checklist-Community	Assess maladaptive behaviors across 5 original subscales: Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/non-compliance, Inappropriate Speech	28 days
OACIS: Ohio Autism Clinical Impression Scale	The OACIS is composed of two scales: the OACIS-Severity scale (OACIS-S), which measures global severity of illness at a given point in time as well as scores for 9 anchors: social interactions; aberrant/abnormal behaviors; repetitive/ritualistic behaviors; verbal communication; non-verbal communication; hyperactivity/inattention; anxiety/fears; sensory sensitivities; restricted and narrow interests and the OACIS improvement scale (OACIS-C), which permits a global evaluation by the clinician of the subject's improvement over time. The OACIS-S is a 7-point scale ranging from 1 (no symptoms) to 7 (very severe). The OACIS-C is a seven-point scale, ranging from 1 (very much improved) to 7 (very much worse).	28 days
CGI-S: Clinical Global Impressions-Severity reflected by the Clinical Global Impressions-Improvement (CGI-I) scale	Illness severity rating is made on a scale of 1 to 7, with 1 being "normal not at all mentally ill" and 7 being "among the most extremely ill patients". Subsequently, the patient's condition on the study drug (or placebo) is compared to the patient's condition before the initiation of the study drug (or placebo) (baseline) via additional CGI-S ratings or the CGI-I item. The CGI is a clinician-rated scale utilizing history from the caregiver and incorporating it into a clinical rating. The CGI-I will be used to judge the change in clinical impression as 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment	28 days
NIH-TCB: NIH Toolbox Cognitive Battery	Computer-based test, that assesses cognition	28 days
KiTAP test battery: The Test of Attentional Performance	The KiTAP test is a computer-based Continuous Performance Tasks (CPT) and Executive Function (EF) battery test	28 days
Social Responsiveness Scale, 2nd Edition (SRS-2)	The SRS-2 is a 65-item parent/caregiver rating scale used to assess the severity of social impairment within patients with ASD.	28 days
CSHQ: Children Sleep Habit Questionnaire	The CSHQ is a retrospective, 45-item parent questionnaire, which includes items relating to a number of key sleep domains that encompass the major presenting clinical sleep complaints in this age group: bedtime behavior and sleep onset; sleep duration; anxiety around sleep; behavior occurring during sleep and night wakings; sleep-disordered breathing; parasomnias; and morning waking/daytime sleepiness.	28 days
EEG: Electroencephalogram	Auditory Event Related Potentials (ERP) will be measured.	28 days
Eye-tracking	Change from baseline in eye gaze to eye regions during viewing of static faces and change in eye gaze to social scene viewing during viewing of dynamic video	28 days
Lactate/Pyruvate Ratio - L:P	Change from baseline, measured in blood	28 days

Collaborators and Investigators

• Sponsor: Stalicla SA

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): January 28, 2022
• Study Completion (Actual): January 28, 2022

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: ASD; Autism Spectrum Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: STP1-C004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No