Trial Outcomes & Findings for Clinical Study Of caNNabidiol in childrEn and adolesCenTs With Fragile X (CONNECT-FX) (NCT NCT03614663)

Results Overview

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 12, and a higher value indicates a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

212 participants

Primary outcome timeframe

Change from Baseline to end of treatment (Week 12)

Results posted on

2022-07-06

Participant Flow

Participant milestones

Participant milestones
Measure	ZYN002 - Cannabidiol Transdermal Gel ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo. ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo Transdermal Gel Matching ZYN002 placebo supplied as a transdermal gel. Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
Overall Study STARTED	110	102
Overall Study COMPLETED	106	99
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ZYN002 - Cannabidiol Transdermal Gel n=110 Participants ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo. ZYN002 - cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo Transdermal Gel n=102 Participants Matching ZYN002 placebo supplied as a transdermal gel. Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)	Total n=212 Participants Total of all reporting groups
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=110 Participants	5 Participants n=102 Participants	14 Participants n=212 Participants
ABC-C FXS Social Avoidance Subscale	7.12 units on a scale STANDARD_DEVIATION 2.71 • n=109 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	7.24 units on a scale STANDARD_DEVIATION 2.80 • n=101 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	7.18 units on a scale STANDARD_DEVIATION 2.75 • n=210 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).
ABC-C FXS Irritability Subscale	28.49 units on a scale STANDARD_DEVIATION 13.10 • n=109 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	27.65 units on a scale STANDARD_DEVIATION 12.96 • n=101 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	28.09 units on a scale STANDARD_DEVIATION 13.01 • n=210 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).
Age, Continuous	9.6 years n=110 Participants	9.8 years n=102 Participants	9.7 years n=212 Participants
Sex: Female, Male Female	29 Participants n=110 Participants	24 Participants n=102 Participants	53 Participants n=212 Participants
Sex: Female, Male Male	81 Participants n=110 Participants	78 Participants n=102 Participants	159 Participants n=212 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=110 Participants	0 Participants n=102 Participants	0 Participants n=212 Participants
Race (NIH/OMB) Asian	1 Participants n=110 Participants	5 Participants n=102 Participants	6 Participants n=212 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=110 Participants	0 Participants n=102 Participants	2 Participants n=212 Participants
Race (NIH/OMB) Black or African American	7 Participants n=110 Participants	4 Participants n=102 Participants	11 Participants n=212 Participants
Race (NIH/OMB) White	85 Participants n=110 Participants	81 Participants n=102 Participants	166 Participants n=212 Participants
Race (NIH/OMB) More than one race	6 Participants n=110 Participants	7 Participants n=102 Participants	13 Participants n=212 Participants
ABC-C FXS Socially Unresponsive / Lethargic	13.42 units on a scale STANDARD_DEVIATION 6.75 • n=109 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	12.82 units on a scale STANDARD_DEVIATION 7.09 • n=101 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).	13.13 units on a scale STANDARD_DEVIATION 6.90 • n=210 Participants • One participant did not receive trial medication and one patient did not have a post-baseline efficacy measure, resulting in 210 participants in the full analysis set (ZYN002: n=109); placebo: n=101).

PRIMARY outcome

Timeframe: Change from Baseline to end of treatment (Week 12)

Population: The prospective comparison of the full analytical set between ZYN002 and placebo.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 12, and a higher value indicates a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=109 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=101 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Full Analysis Set	-2.68 change in score Standard Error 0.310	-2.29 change in score Standard Error 0.318

PRIMARY outcome

Timeframe: Change from baseline to end of treatment (Week 12)

Population: A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 12, and the higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=91 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=76 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Ad Hoc Analysis	-2.99 Change in score Standard Error 0.323	-1.99 Change in score Standard Error 0.345

SECONDARY outcome

Timeframe: Change from baseline to end of treatment (Week 12)

Population: The prospective comparison of the full analytical set between ZYN002 and placebo.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=109 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=101 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Full Analysis Set	-5.88 Change in score Standard Error 0.960	-4.14 Change in score Standard Error 0.984

SECONDARY outcome

Timeframe: Change from baseline to end of treatment (Week 12)

Population: The prospective comparison of the full analytical set between ZYN002 and placebo.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 39, and a higher mean indicates a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=109 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=101 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Full Analysis Set	-3.50 Change in score Standard Error 0.565	-3.14 Change in score Standard Error 0.577

SECONDARY outcome

Timeframe: Change in CGI-I at end of treatment (Week 12)

Population: The prospective comparison of the full analytical set between ZYN002 and placebo.

The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=109 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=101 Participants Placebo formulated as a clear gel (transdermal delivery)
Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Full Analysis Set	46 Participants	37 Participants

SECONDARY outcome

Timeframe: Change from baseline in ABC-C to end of treatment (Week 12)

Population: A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is between 0 and 54, and the higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=91 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=76 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Ad Hoc Analysis	-6.43 Change in score Standard Error 1.020	-4.13 Change in score Standard Error 1.088

SECONDARY outcome

Timeframe: Change from baseline in ABC-C to end of treatment (Week 12)

Population: A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.

The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 39 , and the higher score means a worse outcome.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=91 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=76 Participants Placebo formulated as a clear gel (transdermal delivery)
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Ad Hoc Analysis	-3.91 Change in score Standard Error 0.592	-2.74 Change in score Standard Error 0.631

SECONDARY outcome

Timeframe: Change in CGI-I at end of treatment (Week 12)

Population: A pre-specified, ad hoc analysis of the data collected in patients with ≥90% methylation of the FMR1 gene to evaluate the effect of ZYN002 versus placebo was developed prior to unblinding the trial.

The Clinical Global Impressions- Improvement global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities. The score ranges form 1-very much improved to 7-very much worse. The percentage of patients with any improvement (minimally, much, very much improved) was assessed.

Outcome measures

Outcome measures
Measure	ZYN002 - Cannabidiol Transdermal Gel n=91 Participants ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo n=76 Participants Placebo formulated as a clear gel (transdermal delivery)
Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Ad Hoc Analysis	43 Participants	25 Participants

Adverse Events

ZYN002 - Cannabidiol Transdermal Gel

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Placebo Transdermal Gel

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	ZYN002 - Cannabidiol Transdermal Gel n=109 participants at risk ZYN002 - Cannabidiol Transdermal Gel: Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)	Placebo Transdermal Gel n=102 participants at risk Placebo Transdermal Gel: Placebo formulated as a clear gel (transdermal delivery)
Gastrointestinal disorders vomiting	7.3% 8/109 • Number of events 9 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).	5.9% 6/102 • Number of events 7 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).
General disorders pyrexia	4.6% 5/109 • Number of events 5 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).	6.9% 7/102 • Number of events 7 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).
General disorders application site pain	6.4% 7/109 • Number of events 7 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).	0.98% 1/102 • Number of events 1 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).
Infections and infestations upper respiratory tract infection	13.8% 15/109 • Number of events 16 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).	6.9% 7/102 • Number of events 7 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).
Infections and infestations nasopharyngitis	9.2% 10/109 • Number of events 10 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).	8.8% 9/102 • Number of events 9 • Adverse events were collected up to 18 weeks. Adverse Event Analysis Population Description: 212 patients (ZYN002: n=110; placebo: n=102) were enrolled in the study. One participant did not receive trial medication and is excluded from the safety population, resulting in 211 participants included in safety analysis (ZYN002: n=109); placebo: n=102).

Additional Information

Stephen O'Quinn, PharmD

Zynerba Pharmaceuticals

Phone: 919-271-1339

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60